NO314302B1 - Matriksmetalloproteinase-inhibitorer, anvendelse derav samt farmasöytisk blanding - Google Patents
Matriksmetalloproteinase-inhibitorer, anvendelse derav samt farmasöytisk blanding Download PDFInfo
- Publication number
- NO314302B1 NO314302B1 NO19994125A NO994125A NO314302B1 NO 314302 B1 NO314302 B1 NO 314302B1 NO 19994125 A NO19994125 A NO 19994125A NO 994125 A NO994125 A NO 994125A NO 314302 B1 NO314302 B1 NO 314302B1
- Authority
- NO
- Norway
- Prior art keywords
- methoxy
- piperidine
- benzenesulfonyl
- carboxylic acid
- alkyl
- Prior art date
Links
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title description 3
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 19
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 18
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- -1 4-(4-n-butoxy- benzenesulfonyl)-1-(2-phenyl-ethyl)-piperidin-4-carboxylic Chemical compound 0.000 claims description 15
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 102000004190 Enzymes Human genes 0.000 claims description 8
- 108090000790 Enzymes Proteins 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- WWVKBGIBCFSFOJ-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-n-hydroxy-1-(3-phenoxypropyl)piperidine-4-carboxamide Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCCOC=2C=CC=CC=2)CC1 WWVKBGIBCFSFOJ-UHFFFAOYSA-N 0.000 claims description 4
- NAXMTMYDSBOGMZ-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-n-hydroxy-1-[(4-methoxyphenyl)methyl]piperidine-4-carboxamide Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(OC)=CC=2)CC1 NAXMTMYDSBOGMZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000007943 implant Substances 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- YJOSMOCGEMCNLK-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-(2-phenoxyethyl)piperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCOC=2C=CC=CC=2)CC1 YJOSMOCGEMCNLK-UHFFFAOYSA-N 0.000 claims description 4
- FTWZRZIOCFAVKU-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-(3-phenylpropyl)piperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCCC=2C=CC=CC=2)CC1 FTWZRZIOCFAVKU-UHFFFAOYSA-N 0.000 claims description 4
- 231100000915 pathological change Toxicity 0.000 claims description 4
- 230000036285 pathological change Effects 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- YMQWZRPLMNNHEU-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(Br)=CC=2)CC1 YMQWZRPLMNNHEU-UHFFFAOYSA-N 0.000 claims description 3
- QZAKHVZDCIZWMH-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-1-[(4-fluorophenyl)methyl]-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(F)=CC=2)CC1 QZAKHVZDCIZWMH-UHFFFAOYSA-N 0.000 claims description 3
- 208000020084 Bone disease Diseases 0.000 claims description 3
- 208000031886 HIV Infections Diseases 0.000 claims description 3
- 208000037357 HIV infectious disease Diseases 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- LCQNQVIUMDNDJS-UHFFFAOYSA-N n-hydroxy-1-[(3-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=C(OC)C=CC=2)CC1 LCQNQVIUMDNDJS-UHFFFAOYSA-N 0.000 claims description 3
- VUXKPYYMTYYYCJ-UHFFFAOYSA-N n-hydroxy-1-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CCN1CCC(S(=O)(=O)C=2C=CC(OC)=CC=2)(C(=O)NO)CC1 VUXKPYYMTYYYCJ-UHFFFAOYSA-N 0.000 claims description 3
- FJXZBLKBEVSCAB-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-(3-methylbut-2-enyl)piperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=C(C)C)CC1 FJXZBLKBEVSCAB-UHFFFAOYSA-N 0.000 claims description 3
- CWVWYGJTCDBSIW-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-[(4-methylphenyl)methyl]piperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(C)=CC=2)CC1 CWVWYGJTCDBSIW-UHFFFAOYSA-N 0.000 claims description 3
- PRBMKJZQAUSBQV-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]piperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(OCCN3CCCCC3)=CC=2)CC1 PRBMKJZQAUSBQV-UHFFFAOYSA-N 0.000 claims description 3
- 208000028169 periodontal disease Diseases 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- HYZDHISHDZBYBQ-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(F)=CC=2)CC1 HYZDHISHDZBYBQ-UHFFFAOYSA-N 0.000 claims description 2
- NZSGHPOSLLMCJS-UHFFFAOYSA-N 1-benzyl-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC=CC=2)CC1 NZSGHPOSLLMCJS-UHFFFAOYSA-N 0.000 claims description 2
- 208000025494 Aortic disease Diseases 0.000 claims description 2
- 206010053555 Arthritis bacterial Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000016192 Demyelinating disease Diseases 0.000 claims description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
- 206010015943 Eye inflammation Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 208000022461 Glomerular disease Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000004575 Infectious Arthritis Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 201000002287 Keratoconus Diseases 0.000 claims description 2
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 2
- QDEKTHCPSCGUQA-UHFFFAOYSA-N N-hydroxy-4-(4-methoxyphenyl)sulfonyl-2-methyl-1-naphthalen-2-ylpiperidine-4-carboxamide Chemical group ONC(=O)C1(CC(N(CC1)C1=CC2=CC=CC=C2C=C1)C)S(=O)(=O)C1=CC=C(C=C1)OC QDEKTHCPSCGUQA-UHFFFAOYSA-N 0.000 claims description 2
- 206010029113 Neovascularisation Diseases 0.000 claims description 2
- 206010049088 Osteopenia Diseases 0.000 claims description 2
- 208000003107 Premature Rupture Fetal Membranes Diseases 0.000 claims description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 claims description 2
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 claims description 2
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 2
- 208000022531 anorexia Diseases 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 230000007882 cirrhosis Effects 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 230000003412 degenerative effect Effects 0.000 claims description 2
- 208000024519 eye neoplasm Diseases 0.000 claims description 2
- 231100000852 glomerular disease Toxicity 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 208000001491 myopia Diseases 0.000 claims description 2
- 230000004379 myopia Effects 0.000 claims description 2
- UTDYWIPXAVCYCE-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-[(4-phenylphenyl)methyl]piperidine-4-carboxamide Chemical group C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC(=CC=2)C=2C=CC=CC=2)CC1 UTDYWIPXAVCYCE-UHFFFAOYSA-N 0.000 claims description 2
- RBRSAOMOZVVQSQ-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-methylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C)CC1 RBRSAOMOZVVQSQ-UHFFFAOYSA-N 0.000 claims description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 claims description 2
- 210000000653 nervous system Anatomy 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 claims description 2
- 201000001474 proteinuria Diseases 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 201000001223 septic arthritis Diseases 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- BCOXOPJAJZGIJM-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1CCN(CCCOC=2C=CC=CC=2)CC1 BCOXOPJAJZGIJM-UHFFFAOYSA-N 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 206010060820 Joint injury Diseases 0.000 claims 1
- 206010037660 Pyrexia Diseases 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 230000007505 plaque formation Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
- 238000000034 method Methods 0.000 description 89
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 239000007787 solid Substances 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 43
- 239000003921 oil Substances 0.000 description 39
- 235000019198 oils Nutrition 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 239000000843 powder Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 17
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 10
- 108010026132 Gelatinases Proteins 0.000 description 9
- 102000013382 Gelatinases Human genes 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 102000029816 Collagenase Human genes 0.000 description 6
- 108060005980 Collagenase Proteins 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 5
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 5
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 5
- 229940092714 benzenesulfonic acid Drugs 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229960002424 collagenase Drugs 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 235000009518 sodium iodide Nutrition 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- XVEHBTQWYNXBED-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(4-methoxyphenyl)methyl]ethanamine Chemical compound COC1=CC=C(CN(CCCl)CCCl)C=C1 XVEHBTQWYNXBED-UHFFFAOYSA-N 0.000 description 3
- IHOJMZYAFHCAST-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]ethanamine Chemical compound C1=CC(CN(CCCl)CCCl)=CC=C1OCCN1CCCCC1 IHOJMZYAFHCAST-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 3
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 3
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- URLYFRDHCDGEPS-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-2-phenoxyethanamine Chemical compound ClCCN(CCCl)CCOC1=CC=CC=C1 URLYFRDHCDGEPS-UHFFFAOYSA-N 0.000 description 3
- KLYIBVBIKFMTRO-UHFFFAOYSA-N n-hydroxy-1-[(4-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1CN1CCC(S(=O)(=O)C=2C=CC(OC)=CC=2)(C(=O)NO)CC1 KLYIBVBIKFMTRO-UHFFFAOYSA-N 0.000 description 3
- KASLMAICRUMQME-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-(2-phenylethyl)piperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCC=2C=CC=CC=2)CC1 KASLMAICRUMQME-UHFFFAOYSA-N 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
- 159000000001 potassium salts Chemical class 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 150000003457 sulfones Chemical class 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JSWNZVXGNOTJIM-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 JSWNZVXGNOTJIM-UHFFFAOYSA-N 0.000 description 2
- DUWMUQJJAWJMKE-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=C(OC)C=CC=2)CC1 DUWMUQJJAWJMKE-UHFFFAOYSA-N 0.000 description 2
- IWSJFFNNOGLAOF-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(Br)=CC=2)CC1 IWSJFFNNOGLAOF-UHFFFAOYSA-N 0.000 description 2
- CYUGJLVHBZRKNV-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(F)=CC=2)CC1 CYUGJLVHBZRKNV-UHFFFAOYSA-N 0.000 description 2
- HQAGKFIGCAJZKE-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CN1CCC(S(=O)(=O)C=2C=CC(OC)=CC=2)(C(O)=O)CC1 HQAGKFIGCAJZKE-UHFFFAOYSA-N 0.000 description 2
- BZJNHCZGKWQZOC-UHFFFAOYSA-N 1-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CCN1CCC(S(=O)(=O)C=2C=CC(OC)=CC=2)(C(O)=O)CC1 BZJNHCZGKWQZOC-UHFFFAOYSA-N 0.000 description 2
- FECLWRWFWSXYKU-UHFFFAOYSA-N 1-benzyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC=CC=2)CC1 FECLWRWFWSXYKU-UHFFFAOYSA-N 0.000 description 2
- IRJDDGBEDQOZOG-UHFFFAOYSA-N 1-cyclooctyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C2CCCCCCC2)CC1 IRJDDGBEDQOZOG-UHFFFAOYSA-N 0.000 description 2
- GJICTISPMDMSQH-UHFFFAOYSA-N 1-cyclooctyl-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C2CCCCCCC2)CC1 GJICTISPMDMSQH-UHFFFAOYSA-N 0.000 description 2
- DGPTVADDIGLETM-UHFFFAOYSA-N 1-tert-butyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C(C)(C)C)CC1 DGPTVADDIGLETM-UHFFFAOYSA-N 0.000 description 2
- MLJSRWALBCZDCB-UHFFFAOYSA-N 1-tert-butyl-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C(C)(C)C)CC1 MLJSRWALBCZDCB-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- YXYOXGSDQLJFDP-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methyl-(2-hydroxyethyl)amino]ethanol Chemical compound OCCN(CCO)CC1=CC=C(Cl)C(Cl)=C1 YXYOXGSDQLJFDP-UHFFFAOYSA-N 0.000 description 2
- YOYHVMIRZKMMPG-UHFFFAOYSA-N 2-[(4-bromophenyl)methyl-(2-hydroxyethyl)amino]ethanol Chemical compound OCCN(CCO)CC1=CC=C(Br)C=C1 YOYHVMIRZKMMPG-UHFFFAOYSA-N 0.000 description 2
- VOUWIXZCTHZNEH-UHFFFAOYSA-N 2-[2-hydroxyethyl(2-phenoxyethyl)amino]ethanol Chemical compound OCCN(CCO)CCOC1=CC=CC=C1 VOUWIXZCTHZNEH-UHFFFAOYSA-N 0.000 description 2
- RMLOQPUPBVVMCO-UHFFFAOYSA-N 2-[2-hydroxyethyl(2-phenylethyl)amino]ethanol Chemical compound OCCN(CCO)CCC1=CC=CC=C1 RMLOQPUPBVVMCO-UHFFFAOYSA-N 0.000 description 2
- VDVWWRRBJNNKQD-UHFFFAOYSA-N 2-[2-hydroxyethyl(3-phenylpropyl)amino]ethanol Chemical compound OCCN(CCO)CCCC1=CC=CC=C1 VDVWWRRBJNNKQD-UHFFFAOYSA-N 0.000 description 2
- KORPIWRPEFDZPH-UHFFFAOYSA-N 2-[2-hydroxyethyl-[(3-methoxyphenyl)methyl]amino]ethanol Chemical compound COC1=CC=CC(CN(CCO)CCO)=C1 KORPIWRPEFDZPH-UHFFFAOYSA-N 0.000 description 2
- BRKVKGWERTXEKT-UHFFFAOYSA-N 2-[2-hydroxyethyl-[(4-methoxyphenyl)methyl]amino]ethanol Chemical compound COC1=CC=C(CN(CCO)CCO)C=C1 BRKVKGWERTXEKT-UHFFFAOYSA-N 0.000 description 2
- DUUFGGOWUAPNDI-UHFFFAOYSA-N 2-[2-hydroxyethyl-[(4-methylphenyl)methyl]amino]ethanol Chemical compound CC1=CC=C(CN(CCO)CCO)C=C1 DUUFGGOWUAPNDI-UHFFFAOYSA-N 0.000 description 2
- YAUGGMXSAKUVKA-UHFFFAOYSA-N 2-[2-hydroxyethyl-[2-(4-methoxyphenyl)ethyl]amino]ethanol Chemical compound COC1=CC=C(CCN(CCO)CCO)C=C1 YAUGGMXSAKUVKA-UHFFFAOYSA-N 0.000 description 2
- YUQUNWNSQDULTI-UHFFFAOYSA-N 2-bromobenzenethiol Chemical group SC1=CC=CC=C1Br YUQUNWNSQDULTI-UHFFFAOYSA-N 0.000 description 2
- AIIOOPQZGJBUBD-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(3,4-dichlorophenyl)methyl]ethanamine Chemical compound ClCCN(CCCl)CC1=CC=C(Cl)C(Cl)=C1 AIIOOPQZGJBUBD-UHFFFAOYSA-N 0.000 description 2
- XTUZOBLXVGEQEU-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(3-methoxyphenyl)methyl]ethanamine Chemical compound COC1=CC=CC(CN(CCCl)CCCl)=C1 XTUZOBLXVGEQEU-UHFFFAOYSA-N 0.000 description 2
- XFYLJTALUWPUEI-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(4-fluorophenyl)methyl]ethanamine Chemical compound FC1=CC=C(CN(CCCl)CCCl)C=C1 XFYLJTALUWPUEI-UHFFFAOYSA-N 0.000 description 2
- DDPGQCHQLTZAEW-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-1-(2-phenoxyethyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCOC=2C=CC=CC=2)CC1 DDPGQCHQLTZAEW-UHFFFAOYSA-N 0.000 description 2
- AIZQGRMSEBXCNI-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCCOC=2C=CC=CC=2)CC1 AIZQGRMSEBXCNI-UHFFFAOYSA-N 0.000 description 2
- RLIOBDUNWLJVRN-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-1-[(4-methoxyphenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(OC)=CC=2)CC1 RLIOBDUNWLJVRN-UHFFFAOYSA-N 0.000 description 2
- GMRJGTBNERTZIB-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-n-hydroxy-1-(2-phenoxyethyl)piperidine-4-carboxamide Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCOC=2C=CC=CC=2)CC1 GMRJGTBNERTZIB-UHFFFAOYSA-N 0.000 description 2
- AEMURECWAJLPNX-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(2-phenoxyethyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCOC=2C=CC=CC=2)CC1 AEMURECWAJLPNX-UHFFFAOYSA-N 0.000 description 2
- NIAJIVRYYJLXRC-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(2-phenylethyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCC=2C=CC=CC=2)CC1 NIAJIVRYYJLXRC-UHFFFAOYSA-N 0.000 description 2
- JBQHDBBLSWCKPO-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(3-methylbut-2-enyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=C(C)C)CC1 JBQHDBBLSWCKPO-UHFFFAOYSA-N 0.000 description 2
- ZONWCAFXWCFRRI-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCCOC=2C=CC=CC=2)CC1 ZONWCAFXWCFRRI-UHFFFAOYSA-N 0.000 description 2
- YENBIMVFSZPGNF-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(3-phenylpropyl)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CCCC=2C=CC=CC=2)CC1 YENBIMVFSZPGNF-UHFFFAOYSA-N 0.000 description 2
- HKMTZJUWMOYMCB-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-[(4-methylphenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(C)=CC=2)CC1 HKMTZJUWMOYMCB-UHFFFAOYSA-N 0.000 description 2
- JXNPCFNODXHENK-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-[(4-phenylphenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(=CC=2)C=2C=CC=CC=2)CC1 JXNPCFNODXHENK-UHFFFAOYSA-N 0.000 description 2
- ZPYAYNWVYRRKRN-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C(C)C)CC1 ZPYAYNWVYRRKRN-UHFFFAOYSA-N 0.000 description 2
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 2
- 108091007505 ADAM17 Proteins 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 150000001543 aryl boronic acids Chemical class 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- AZRWNJFEUSHORT-UHFFFAOYSA-N benzyl-bis(2-chloroethyl)azanium;chloride Chemical compound [Cl-].ClCC[NH+](CCCl)CC1=CC=CC=C1 AZRWNJFEUSHORT-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- HRSATTGHPSBTNO-UHFFFAOYSA-N ethyl 1-[(3,4-dichlorophenyl)methyl]-4-(2-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C(=CC=CC=2)OC)CCN1CC1=CC=C(Cl)C(Cl)=C1 HRSATTGHPSBTNO-UHFFFAOYSA-N 0.000 description 2
- RGPVWHXPNBITTA-UHFFFAOYSA-N ethyl 1-[(3-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=CC(OC)=C1 RGPVWHXPNBITTA-UHFFFAOYSA-N 0.000 description 2
- LYLYNHJJCZKNAF-UHFFFAOYSA-N ethyl 1-[(4-bromophenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=C(Br)C=C1 LYLYNHJJCZKNAF-UHFFFAOYSA-N 0.000 description 2
- YRXBNIRWFMHAMS-UHFFFAOYSA-N ethyl 1-[(4-methoxyphenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=C(OC)C=C1 YRXBNIRWFMHAMS-UHFFFAOYSA-N 0.000 description 2
- RNUGWNKLIKCKOV-UHFFFAOYSA-N ethyl 1-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CCC1=CC=C(OC)C=C1 RNUGWNKLIKCKOV-UHFFFAOYSA-N 0.000 description 2
- MVWUKKXTCAGNNJ-UHFFFAOYSA-N ethyl 1-[[4-(4-methoxyphenyl)sulfonylnaphthalen-1-yl]methyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1CC1=CC=C(S(=O)(=O)C=2C=CC(OC)=CC=2)C2=CC=CC=C12 MVWUKKXTCAGNNJ-UHFFFAOYSA-N 0.000 description 2
- GNWSAGQKHSUVLT-UHFFFAOYSA-N ethyl 1-benzyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=CC=C1 GNWSAGQKHSUVLT-UHFFFAOYSA-N 0.000 description 2
- FVNQRHTZLGYVPB-UHFFFAOYSA-N ethyl 1-butyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CN(CCCC)CCC1(C(=O)OCC)S(=O)(=O)C1=CC=C(OC)C=C1 FVNQRHTZLGYVPB-UHFFFAOYSA-N 0.000 description 2
- NUXWDBFBHPVLBS-UHFFFAOYSA-N ethyl 1-cyclooctyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1C1CCCCCCC1 NUXWDBFBHPVLBS-UHFFFAOYSA-N 0.000 description 2
- MFDBJTGAQFVAEB-UHFFFAOYSA-N ethyl 2-(4-methoxyphenyl)sulfanylacetate Chemical compound CCOC(=O)CSC1=CC=C(OC)C=C1 MFDBJTGAQFVAEB-UHFFFAOYSA-N 0.000 description 2
- HJUXYQLTIVYHIN-UHFFFAOYSA-N ethyl 2-(4-methoxyphenyl)sulfonylacetate Chemical compound CCOC(=O)CS(=O)(=O)C1=CC=C(OC)C=C1 HJUXYQLTIVYHIN-UHFFFAOYSA-N 0.000 description 2
- ILOBLRACMDRJCE-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-(2-phenylethyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CCC1=CC=CC=C1 ILOBLRACMDRJCE-UHFFFAOYSA-N 0.000 description 2
- OBLAEDSPDBRSER-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-(3-methylbut-2-enyl)piperidine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)C1(C(=O)OCC)CCN(CC=C(C)C)CC1 OBLAEDSPDBRSER-UHFFFAOYSA-N 0.000 description 2
- XVOZQUFANNBYBM-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CCCOC1=CC=CC=C1 XVOZQUFANNBYBM-UHFFFAOYSA-N 0.000 description 2
- QJEGYSPYCYGEQL-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-(3-phenylpropyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CCCC1=CC=CC=C1 QJEGYSPYCYGEQL-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- QZPCOIZZKYRYQH-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C(C(C)N(CCCl)CCCl)C=C1 QZPCOIZZKYRYQH-UHFFFAOYSA-N 0.000 description 2
- BSXSSXPCEVBUSF-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-2-methylpropan-2-amine Chemical compound ClCCN(C(C)(C)C)CCCl BSXSSXPCEVBUSF-UHFFFAOYSA-N 0.000 description 2
- NSYROPDQXYIHMF-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-2-phenylethanamine Chemical compound ClCCN(CCCl)CCC1=CC=CC=C1 NSYROPDQXYIHMF-UHFFFAOYSA-N 0.000 description 2
- SFQOTBMYWKTJKF-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-3-phenoxypropan-1-amine Chemical compound ClCCN(CCCl)CCCOC1=CC=CC=C1 SFQOTBMYWKTJKF-UHFFFAOYSA-N 0.000 description 2
- SXPGFJZLDDFUHA-UHFFFAOYSA-N n,n-bis(2-chloroethyl)butan-1-amine Chemical compound CCCCN(CCCl)CCCl SXPGFJZLDDFUHA-UHFFFAOYSA-N 0.000 description 2
- JZLVPSUROKRFMZ-UHFFFAOYSA-N n,n-bis(2-chloroethyl)cyclooctanamine Chemical compound ClCCN(CCCl)C1CCCCCCC1 JZLVPSUROKRFMZ-UHFFFAOYSA-N 0.000 description 2
- FBLQAKOTTHGGBJ-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CCCOC=2C=CC=CC=2)CC1 FBLQAKOTTHGGBJ-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- YZIFVWOCPGPNHB-UHFFFAOYSA-N 1,2-dichloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C(Cl)=C1 YZIFVWOCPGPNHB-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- PMIAMRAWHYEPNH-UHFFFAOYSA-N 1-(2-chloroethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCCl)C=C1 PMIAMRAWHYEPNH-UHFFFAOYSA-N 0.000 description 1
- VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- DMHZDOTYAVHSEH-UHFFFAOYSA-N 1-(chloromethyl)-4-methylbenzene Chemical compound CC1=CC=C(CCl)C=C1 DMHZDOTYAVHSEH-UHFFFAOYSA-N 0.000 description 1
- HLQZCRVEEQKNMS-UHFFFAOYSA-N 1-(chloromethyl)-4-phenylbenzene Chemical group C1=CC(CCl)=CC=C1C1=CC=CC=C1 HLQZCRVEEQKNMS-UHFFFAOYSA-N 0.000 description 1
- NPFGSGCFKYSLPI-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 NPFGSGCFKYSLPI-UHFFFAOYSA-N 0.000 description 1
- CVXCWPZVOYBWOJ-UHFFFAOYSA-N 1-[2-[4-(chloromethyl)phenoxy]ethyl]piperidine Chemical compound C1=CC(CCl)=CC=C1OCCN1CCCCC1 CVXCWPZVOYBWOJ-UHFFFAOYSA-N 0.000 description 1
- SRPXVKQVZQEPFT-UHFFFAOYSA-N 1-benzyl-4-(4-butoxyphenyl)sulfonyl-n-hydroxypiperidine-4-carboxamide Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(CC=2C=CC=CC=2)CC1 SRPXVKQVZQEPFT-UHFFFAOYSA-N 0.000 description 1
- XRTDXBYJYXOWDU-UHFFFAOYSA-N 1-benzyl-4-(4-butoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC=CC=2)CC1 XRTDXBYJYXOWDU-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- IIASCQBFNHWZBE-UHFFFAOYSA-N 1-bromoethyl acetate Chemical compound CC(Br)OC(C)=O IIASCQBFNHWZBE-UHFFFAOYSA-N 0.000 description 1
- BSCVECPSZUDOGB-UHFFFAOYSA-N 1-butyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1CN(CCCC)CCC1(C(O)=O)S(=O)(=O)C1=CC=C(OC)C=C1 BSCVECPSZUDOGB-UHFFFAOYSA-N 0.000 description 1
- UZVVYDVVOHQVFV-UHFFFAOYSA-N 1-butyl-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1CN(CCCC)CCC1(C(=O)NO)S(=O)(=O)C1=CC=C(OC)C=C1 UZVVYDVVOHQVFV-UHFFFAOYSA-N 0.000 description 1
- DWPQQYLEUVZYGC-UHFFFAOYSA-N 1-ethyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylic acid Chemical compound C1CN(CC)CCC1(C(O)=O)S(=O)(=O)C1=CC=C(OC)C=C1 DWPQQYLEUVZYGC-UHFFFAOYSA-N 0.000 description 1
- MWFBMGWABXFCCK-UHFFFAOYSA-N 1-ethyl-n-hydroxy-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxamide Chemical compound C1CN(CC)CCC1(C(=O)NO)S(=O)(=O)C1=CC=C(OC)C=C1 MWFBMGWABXFCCK-UHFFFAOYSA-N 0.000 description 1
- DPSFVRWDVCJXKC-UHFFFAOYSA-N 2-[2-hydroxyethyl(3-phenoxypropyl)amino]ethanol Chemical compound OCCN(CCO)CCCOC1=CC=CC=C1 DPSFVRWDVCJXKC-UHFFFAOYSA-N 0.000 description 1
- MIZIOHLLYXVEHJ-UHFFFAOYSA-N 2-[benzyl(2-hydroxyethyl)amino]ethanol Chemical compound OCCN(CCO)CC1=CC=CC=C1 MIZIOHLLYXVEHJ-UHFFFAOYSA-N 0.000 description 1
- GVNHOISKXMSMPX-UHFFFAOYSA-N 2-[butyl(2-hydroxyethyl)amino]ethanol Chemical compound CCCCN(CCO)CCO GVNHOISKXMSMPX-UHFFFAOYSA-N 0.000 description 1
- UTOSHYLAYAOIJO-UHFFFAOYSA-N 2-[cyclooctyl(2-hydroxyethyl)amino]ethanol Chemical compound OCCN(CCO)C1CCCCCCC1 UTOSHYLAYAOIJO-UHFFFAOYSA-N 0.000 description 1
- JDNKGGWYOJDWLC-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-(naphthalen-1-ylmethyl)ethanamine Chemical compound C1=CC=C2C(CN(CCCl)CCCl)=CC=CC2=C1 JDNKGGWYOJDWLC-UHFFFAOYSA-N 0.000 description 1
- VUZQZEAXMQHUMJ-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(4-methylphenyl)methyl]ethanamine Chemical compound CC1=CC=C(CN(CCCl)CCCl)C=C1 VUZQZEAXMQHUMJ-UHFFFAOYSA-N 0.000 description 1
- NNBBBGITTCDWNO-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-[(4-phenylphenyl)methyl]ethanamine Chemical compound C1=CC(CN(CCCl)CCCl)=CC=C1C1=CC=CC=C1 NNBBBGITTCDWNO-UHFFFAOYSA-N 0.000 description 1
- UQZPGHOJMQTOHB-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)-n-ethylethanamine Chemical compound ClCCN(CC)CCCl UQZPGHOJMQTOHB-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- WJTZZPVVTSDNJJ-UHFFFAOYSA-N 2-fluorobenzenethiol Chemical group FC1=CC=CC=C1S WJTZZPVVTSDNJJ-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- VMKYTRPNOVFCGZ-UHFFFAOYSA-N 2-sulfanylphenol Chemical group OC1=CC=CC=C1S VMKYTRPNOVFCGZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 1
- XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 description 1
- WNMXWPBLGZBPEV-UHFFFAOYSA-N 4-(4-butoxyphenyl)sulfonyl-1-[(4-fluorophenyl)methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(F)=CC=2)CC1 WNMXWPBLGZBPEV-UHFFFAOYSA-N 0.000 description 1
- XACROVTUKHAMBP-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-(2-phenylethoxy)piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(OCCC=2C=CC=CC=2)CC1 XACROVTUKHAMBP-UHFFFAOYSA-N 0.000 description 1
- UZZOWBRNVGRWPV-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(CC=2C=CC(OCCN3CCCCC3)=CC=2)CC1 UZZOWBRNVGRWPV-UHFFFAOYSA-N 0.000 description 1
- FJKQZMAMXQZOFD-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-1-methylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CCN(C)CC1 FJKQZMAMXQZOFD-UHFFFAOYSA-N 0.000 description 1
- WBTLASDHZWDFMT-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfonyl-2-methyl-1-naphthalen-2-ylpiperidine-4-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(O)=O)CC(C)N(C=2C=C3C=CC=CC3=CC=2)CC1 WBTLASDHZWDFMT-UHFFFAOYSA-N 0.000 description 1
- SVJKMLBXJJZCHN-UHFFFAOYSA-N 4-(aminomethyl)benzenesulfonamide;propanoic acid Chemical group CCC(O)=O.NCC1=CC=C(S(N)(=O)=O)C=C1 SVJKMLBXJJZCHN-UHFFFAOYSA-N 0.000 description 1
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 description 1
- IZMWJUPSQXIVDN-UHFFFAOYSA-N 4-bromo-2-methylbut-1-ene Chemical compound CC(=C)CCBr IZMWJUPSQXIVDN-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
- BXAVKNRWVKUTLY-UHFFFAOYSA-N 4-sulfanylphenol Chemical compound OC1=CC=C(S)C=C1 BXAVKNRWVKUTLY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- SGAPAPYCVDQWNN-UHFFFAOYSA-N C(C)OC(=O)C1(CCN(CC1)CC)S(=O)(=O)C1=CC=C(C=C1)OC.ONC(=O)C1(CCN(CC1)CC)S(=O)(=O)C1=CC=C(C=C1)OC Chemical compound C(C)OC(=O)C1(CCN(CC1)CC)S(=O)(=O)C1=CC=C(C=C1)OC.ONC(=O)C1(CCN(CC1)CC)S(=O)(=O)C1=CC=C(C=C1)OC SGAPAPYCVDQWNN-UHFFFAOYSA-N 0.000 description 1
- CTFXLAAKPCHIDP-UHFFFAOYSA-N C(C)OC(=O)C1(CCN(CC1)CC1=CC=C(C=C1)F)S(=O)(=O)C1=CC=C(C=C1)OCCCC.ONC(=O)C1(CCN(CC1)CC1=CC=C(C=C1)F)S(=O)(=O)C1=CC=C(C=C1)OCCCC Chemical compound C(C)OC(=O)C1(CCN(CC1)CC1=CC=C(C=C1)F)S(=O)(=O)C1=CC=C(C=C1)OCCCC.ONC(=O)C1(CCN(CC1)CC1=CC=C(C=C1)F)S(=O)(=O)C1=CC=C(C=C1)OCCCC CTFXLAAKPCHIDP-UHFFFAOYSA-N 0.000 description 1
- SBQXSTRZTUDLLL-UHFFFAOYSA-N C(C)OC(=O)C1(CCN(CC1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)OCCCC.ONC(=O)C1(CCN(CC1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)OCCCC Chemical compound C(C)OC(=O)C1(CCN(CC1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)OCCCC.ONC(=O)C1(CCN(CC1)CC1=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)OCCCC SBQXSTRZTUDLLL-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 241000982822 Ficus obtusifolia Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 229910017912 NH2OH Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- JAVMYQBDIKNJKN-UHFFFAOYSA-N ethyl 1-[(4-fluorophenyl)methyl]-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=C(F)C=C1 JAVMYQBDIKNJKN-UHFFFAOYSA-N 0.000 description 1
- YRIRCZNJTKIDMG-UHFFFAOYSA-N ethyl 1-benzyl-4-(4-butoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(CC=2C=CC=CC=2)CC1 YRIRCZNJTKIDMG-UHFFFAOYSA-N 0.000 description 1
- MSZXFLPUTGBOCD-UHFFFAOYSA-N ethyl 1-tert-butyl-4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)C1(C(=O)OCC)CCN(C(C)(C)C)CC1 MSZXFLPUTGBOCD-UHFFFAOYSA-N 0.000 description 1
- ZNGFQHMFLDYWDH-UHFFFAOYSA-N ethyl 2-(4-methoxyphenyl)sulfonyl-1-[(4-phenylphenyl)methyl]piperidine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)C1CC(C(=O)OCC)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 ZNGFQHMFLDYWDH-UHFFFAOYSA-N 0.000 description 1
- ZQHXCTLYCWWBDB-UHFFFAOYSA-N ethyl 2-sulfonylacetate Chemical class CCOC(=O)C=S(=O)=O ZQHXCTLYCWWBDB-UHFFFAOYSA-N 0.000 description 1
- KHHADIVHVMPMRM-UHFFFAOYSA-N ethyl 4-(4-butoxyphenyl)sulfonyl-1-(2-phenoxyethyl)piperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(CCOC=2C=CC=CC=2)CC1 KHHADIVHVMPMRM-UHFFFAOYSA-N 0.000 description 1
- FWHUHOBZYWQXCG-UHFFFAOYSA-N ethyl 4-(4-butoxyphenyl)sulfonyl-1-(2-phenylethoxy)piperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(OCCC=2C=CC=CC=2)CC1 FWHUHOBZYWQXCG-UHFFFAOYSA-N 0.000 description 1
- QQUKJPDPCXYTIS-UHFFFAOYSA-N ethyl 4-(4-butoxyphenyl)sulfonyl-1-(3-phenoxypropyl)piperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(CCCOC=2C=CC=CC=2)CC1 QQUKJPDPCXYTIS-UHFFFAOYSA-N 0.000 description 1
- CGTUSHQZZDHNDJ-UHFFFAOYSA-N ethyl 4-(4-butoxyphenyl)sulfonyl-1-[(4-fluorophenyl)methyl]piperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(CC=2C=CC(F)=CC=2)CC1 CGTUSHQZZDHNDJ-UHFFFAOYSA-N 0.000 description 1
- HSTSPDIMHZEZDT-UHFFFAOYSA-N ethyl 4-(4-butoxyphenyl)sulfonyl-1-[(4-methoxyphenyl)methyl]piperidine-4-carboxylate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)C1(C(=O)OCC)CCN(CC=2C=CC(OC)=CC=2)CC1 HSTSPDIMHZEZDT-UHFFFAOYSA-N 0.000 description 1
- RKGXYKXFAZIFTJ-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-(2-phenoxyethyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CCOC1=CC=CC=C1 RKGXYKXFAZIFTJ-UHFFFAOYSA-N 0.000 description 1
- QXGVVHCUURXJMC-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-[(4-methylphenyl)methyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC1=CC=C(C)C=C1 QXGVVHCUURXJMC-UHFFFAOYSA-N 0.000 description 1
- MFMDAOMSCGOFGX-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-[(4-phenylphenyl)methyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC(C=C1)=CC=C1C1=CC=CC=C1 MFMDAOMSCGOFGX-UHFFFAOYSA-N 0.000 description 1
- VERVFCODAACEKU-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)(S(=O)(=O)C=2C=CC(OC)=CC=2)CCN1CC(C=C1)=CC=C1OCCN1CCCCC1 VERVFCODAACEKU-UHFFFAOYSA-N 0.000 description 1
- URNMBYWPWHBBHU-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)C1(C(=O)OCC)CCN(C(C)C)CC1 URNMBYWPWHBBHU-UHFFFAOYSA-N 0.000 description 1
- AFNKMWNGHGDSID-UHFFFAOYSA-N ethyl 4-(4-methoxyphenyl)sulfonylpiperidine-4-carboxylate Chemical compound C=1C=C(OC)C=CC=1S(=O)(=O)C1(C(=O)OCC)CCNCC1 AFNKMWNGHGDSID-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical class 0.000 description 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002349 hydroxyamino group Chemical class [H]ON([H])[*] 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- RMLSUSLMYJAJNW-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-3-methylbut-2-en-1-amine Chemical compound CC(C)=CCN(CCCl)CCCl RMLSUSLMYJAJNW-UHFFFAOYSA-N 0.000 description 1
- APMORDWSEGHCAQ-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-3-phenylpropan-1-amine Chemical compound ClCCN(CCCl)CCCC1=CC=CC=C1 APMORDWSEGHCAQ-UHFFFAOYSA-N 0.000 description 1
- WAEDMQMDOHQPFL-UHFFFAOYSA-N n,n-bis(2-chloroethyl)propan-2-amine Chemical compound ClCCN(C(C)C)CCCl WAEDMQMDOHQPFL-UHFFFAOYSA-N 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- OABJAIADVRIARX-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]-2-chloro-n-(2-chloroethyl)ethanamine Chemical compound ClCCN(CCCl)CC1=CC=C(Br)C=C1 OABJAIADVRIARX-UHFFFAOYSA-N 0.000 description 1
- BSIZUMJRKYHEBR-QGZVFWFLSA-N n-hydroxy-2(r)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)amino]-3-methylbutanamide hydrochloride Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N([C@H](C(C)C)C(=O)NO)CC1=CC=CN=C1 BSIZUMJRKYHEBR-QGZVFWFLSA-N 0.000 description 1
- QUKJNGDEQKDQGY-UHFFFAOYSA-N n-hydroxy-2-sulfonylacetamide Chemical class ONC(=O)C=S(=O)=O QUKJNGDEQKDQGY-UHFFFAOYSA-N 0.000 description 1
- IEGOFALJZJPJJD-UHFFFAOYSA-N n-hydroxy-4-(4-methoxyphenyl)sulfonyl-1-propan-2-ylpiperidine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1(C(=O)NO)CCN(C(C)C)CC1 IEGOFALJZJPJJD-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012663 orally bioavailable inhibitor Substances 0.000 description 1
- 229940044205 orally bioavailable inhibitor Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
- C07D211/66—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having a hetero atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/28—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
- C07D277/74—Sulfur atoms substituted by carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Biotechnology (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Nutrition Science (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US80672897A | 1997-02-27 | 1997-02-27 | |
PCT/US1998/002987 WO1998037877A1 (en) | 1997-02-27 | 1998-02-17 | N-hydroxy-2-(alkyl, aryl or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
NO994125D0 NO994125D0 (no) | 1999-08-26 |
NO994125L NO994125L (no) | 1999-10-26 |
NO314302B1 true NO314302B1 (no) | 2003-03-03 |
Family
ID=25194722
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19994125A NO314302B1 (no) | 1997-02-27 | 1999-08-26 | Matriksmetalloproteinase-inhibitorer, anvendelse derav samt farmasöytisk blanding |
NO19994124A NO314258B1 (no) | 1997-02-27 | 1999-08-26 | N-hydroksy-2-(alkyl, aryl eller heteroarylsulfanyl, sulfinyl eller sulfonyl)-3-substituerte alkyl, aryl eller heteroarylamider, anvendelsederav og farmasöytiske preparater inneholdende disse |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19994124A NO314258B1 (no) | 1997-02-27 | 1999-08-26 | N-hydroksy-2-(alkyl, aryl eller heteroarylsulfanyl, sulfinyl eller sulfonyl)-3-substituerte alkyl, aryl eller heteroarylamider, anvendelsederav og farmasöytiske preparater inneholdende disse |
Country Status (31)
Country | Link |
---|---|
EP (2) | EP0973512B1 (da) |
JP (2) | JP2001519777A (da) |
KR (2) | KR20000075808A (da) |
CN (2) | CN1252790A (da) |
AR (1) | AR011451A1 (da) |
AT (2) | ATE256107T1 (da) |
AU (2) | AU748998B2 (da) |
BG (2) | BG103757A (da) |
BR (2) | BR9807803A (da) |
CA (2) | CA2282656A1 (da) |
CY (1) | CY2477B1 (da) |
DE (2) | DE69820424T2 (da) |
DK (2) | DK0973512T3 (da) |
EA (2) | EA003836B1 (da) |
EE (2) | EE04150B1 (da) |
ES (2) | ES2212274T3 (da) |
GE (2) | GEP20022627B (da) |
HK (1) | HK1024875A1 (da) |
HU (2) | HUP0002092A3 (da) |
IL (2) | IL131257A0 (da) |
NO (2) | NO314302B1 (da) |
NZ (2) | NZ337336A (da) |
PL (2) | PL335401A1 (da) |
PT (2) | PT973512E (da) |
SK (2) | SK115899A3 (da) |
TR (2) | TR199902095T2 (da) |
TW (1) | TW568900B (da) |
UA (1) | UA58543C2 (da) |
WO (2) | WO1998037877A1 (da) |
YU (2) | YU41099A (da) |
ZA (2) | ZA981625B (da) |
Families Citing this family (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6696449B2 (en) | 1997-03-04 | 2004-02-24 | Pharmacia Corporation | Sulfonyl aryl hydroxamates and their use as matrix metalloprotease inhibitors |
US6794511B2 (en) | 1997-03-04 | 2004-09-21 | G. D. Searle | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
US7115632B1 (en) | 1999-05-12 | 2006-10-03 | G. D. Searle & Co. | Sulfonyl aryl or heteroaryl hydroxamic acid compounds |
WO1998039315A1 (en) * | 1997-03-04 | 1998-09-11 | Monsanto Company | Aromatic sulfonyl alpha-cycloamino hydroxamic acid compounds |
DK0973392T3 (da) * | 1997-03-04 | 2004-03-29 | Monsanto Co | Divalente sulfonyl-aryl eller heteroarylhydroxamsyreforbindelser |
US6005102A (en) | 1997-10-15 | 1999-12-21 | American Home Products Corporation | Aryloxy-alkyl-dialkylamines |
JP2001519410A (ja) * | 1997-10-15 | 2001-10-23 | アメリカン・ホーム・プロダクツ・コーポレイション | 新規なアリールオキシ−アルキル−ジアルキルアミン |
US6750228B1 (en) * | 1997-11-14 | 2004-06-15 | Pharmacia Corporation | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
US20010039287A1 (en) | 1997-11-14 | 2001-11-08 | Thomas E Barta | Aromatic sulfone hydroxamic acid metalloprotease inhibitor |
BR9814643A (pt) * | 1997-11-14 | 2000-10-03 | Searle & Co | Inibidor de metaloprotease de ácido sulfona hidroxâmico aromático |
GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
IL137566A0 (en) * | 1998-02-19 | 2001-07-24 | American Cyanamid Co | N-hydroxy-2-(alkyl, aryl or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted-alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors |
DK1004578T3 (da) * | 1998-11-05 | 2004-06-28 | Pfizer Prod Inc | 5-oxo-pyrrolidin-2-carboxylsyrehydroxamidderivater |
AR035312A1 (es) * | 1999-01-27 | 2004-05-12 | Wyeth Corp | Compuestos de acido hidroxamico que contienen alquinilo como inhibidores de metaloproteinasa de matriz/tace, composicion farmaceutica que los comprenden y el uso de los mismos para la manufactura de un medicamento |
AR035311A1 (es) * | 1999-01-27 | 2004-05-12 | Wyeth Corp | Derivados de acido hidroxamico que contienen alquinilo, como inhibidores de las metalloproteinasas de matriz y de la tace, composicion farmaceutica y el uso de los mismos para la manufactura de un medicamento |
US6340691B1 (en) | 1999-01-27 | 2002-01-22 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors |
US6946473B2 (en) | 1999-01-27 | 2005-09-20 | Wyeth Holdings Corporation | Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors |
US6753337B2 (en) | 1999-01-27 | 2004-06-22 | Wyeth Holdings Corporation | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors |
US6358980B1 (en) * | 1999-01-27 | 2002-03-19 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors |
EE200100410A (et) | 1999-02-08 | 2002-12-16 | G.D. Searle & Co. | Sulfamaathüdroksaamhappe metalloproteaasi inhibiitor |
US6800646B1 (en) | 1999-02-08 | 2004-10-05 | Pharmacia Corporation | Sulfamato hydroxamic acid metalloprotease inhibitor |
SE9901572D0 (sv) | 1999-05-03 | 1999-05-03 | Astra Ab | New compounds |
US6511993B1 (en) | 1999-06-03 | 2003-01-28 | Kevin Neil Dack | Metalloprotease inhibitors |
AU2001233034A1 (en) * | 2000-01-27 | 2001-08-07 | American Cyanamid Company | Method for preparing alpha-sulfonyl hydroxamic acid derivatives |
US6683093B2 (en) | 2000-05-12 | 2004-01-27 | Pharmacia Corporation | Aromatic sulfone hydroxamic acids and their use as protease inhibitors |
WO2002092588A2 (en) | 2001-05-11 | 2002-11-21 | Pharmacia Corporation | Aromatic sulfone hydroxamates and their use as protease inhibitors |
US6683078B2 (en) | 2001-07-19 | 2004-01-27 | Pharmacia Corporation | Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors |
EP2324830A1 (en) | 2002-03-05 | 2011-05-25 | TransTech Pharma Inc. | Process for the preparation of a monocyclic azole derivative that inhibits the interaction of ligands with rage |
US7119203B2 (en) | 2002-04-25 | 2006-10-10 | Pharmacia Corporation | Piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors |
EP1515951A1 (en) * | 2002-06-25 | 2005-03-23 | Pharmacia Corporation | Arylsulfonylhydroxamic acid and amide derivatives and their use as protease inhibitors |
US7098241B2 (en) | 2002-12-16 | 2006-08-29 | Hoffmann-La Roche Inc. | Thiophene hydroxamic acid derivatives |
US7423176B2 (en) | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
JP2009519349A (ja) | 2005-12-15 | 2009-05-14 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を変調する化合物 |
CA2657247A1 (en) | 2006-07-28 | 2008-01-31 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
EP2074084B1 (en) | 2006-09-25 | 2013-08-28 | Boehringer Ingelheim International GmbH | Compounds which modulate the cb2 receptor |
US7803793B2 (en) | 2006-10-05 | 2010-09-28 | Janssen Pharmaceutica Nv | Heterocyclic derived metalloprotease inhibitors |
WO2009008905A1 (en) * | 2007-02-01 | 2009-01-15 | Panthera Biopharma, Llc. | Hydroxamic acid derivatives of phenoxy-acetic acids and analogs useful as therapeutic agents for treating anthrax poisoning |
CA2704684A1 (en) | 2007-11-07 | 2009-05-14 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
US8178568B2 (en) | 2008-07-10 | 2012-05-15 | Boehringer Ingelheim International Gmbh | Sulfone compounds which modulate the CB2 receptor |
WO2010036631A2 (en) | 2008-09-25 | 2010-04-01 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the cb2 receptor |
US8299103B2 (en) | 2009-06-15 | 2012-10-30 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the CB2 receptor |
EP2443107B1 (en) | 2009-06-16 | 2018-08-08 | Boehringer Ingelheim International GmbH | Azetidine 2 -carboxamide derivatives which modulate the cb2 receptor |
US8383651B2 (en) | 2009-09-22 | 2013-02-26 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the CB2 receptor |
WO2011041198A1 (en) | 2009-09-30 | 2011-04-07 | Transtech Pharma, Inc. | Substituted imidazole derivatives for treatment of alzheimers disease |
WO2011045703A2 (en) * | 2009-10-13 | 2011-04-21 | Pfizer Inc. | C-linked hydroxamic acid derivatives useful as antibacterial agents |
JP2013517271A (ja) | 2010-01-15 | 2013-05-16 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を調節する化合物 |
US8329735B2 (en) | 2010-03-05 | 2012-12-11 | Boehringer Ingelheim International Gmbh | Tetrazole compounds which selectively modulate the CB2 receptor |
WO2012012307A1 (en) | 2010-07-22 | 2012-01-26 | Boehringer Ingelheim International Gmbh | Sulfonyl compounds which modulate the cb2 rece |
US9034922B2 (en) * | 2010-09-17 | 2015-05-19 | The University Of Tokyo | Composition for maintaining function of platelets |
CA2917604C (en) * | 2012-07-18 | 2021-08-10 | Josune Orbe Lopategui | New antifibrinolytic compounds |
EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
EA201692305A1 (ru) | 2014-05-16 | 2017-05-31 | Актелион Фармасьютиклз Лтд. | Антибактериальные хиназолин-4(3н)-оновые производные |
CN107188837B (zh) * | 2017-06-06 | 2019-05-28 | 温州大学 | 一种α-酰基高烯丙基硫醚类化合物的合成方法 |
WO2020070239A1 (en) | 2018-10-04 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS50121218A (da) * | 1974-03-01 | 1975-09-23 | ||
DE2424742C3 (de) * | 1974-05-21 | 1982-04-22 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Thiophenderivate Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
US3994997A (en) * | 1975-05-09 | 1976-11-30 | Gulf Oil Corporation | O,O-diethyl-O-carboxamidophosphate esters |
GB1520812A (en) * | 1975-10-02 | 1978-08-09 | Lafon Labor | Benzhydrylsulphinyl derivatives |
GB1574822A (en) * | 1976-03-23 | 1980-09-10 | Lafon Labor | Acetohydroxamic acid derivatives and pharmaceutical compositions thereof |
FR2528041A1 (fr) * | 1982-06-04 | 1983-12-09 | Lafon Labor | Acides halogenobenzhydrylsulfinylacetohydroxamiques, procede de preparation et utilisation en therapeutique |
FR2561646B1 (fr) * | 1984-03-23 | 1987-10-09 | Lafon Labor | Derives d'acide (a-(alkylaminomethyl)-benzyl)-thioacetique, procede de preparation et utilisation en therapeutique |
IL92915A0 (en) * | 1989-01-05 | 1990-09-17 | Ciba Geigy Ag | Certain pyrrolylphenyl-substituted hydroxamic acid derivatives |
DE69309047T2 (de) * | 1992-04-07 | 1997-09-11 | British Biotech Pharm | Hydroxamsäure enthaltende collagenase-inhibitoren und cytokinaktivitätsinhibitoren |
US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
FR2708201B1 (fr) * | 1993-06-30 | 1995-10-20 | Lafon Labor | Utilisation de dérivés d'acétamide pour la fabrication de médicaments. |
GB9416897D0 (en) * | 1994-08-20 | 1994-10-12 | British Biotech Pharm | Metalloproteinase inhibitors |
WO1996035714A1 (en) * | 1995-05-10 | 1996-11-14 | Chiroscience Limited | Peptide compounds which inhibit metalloproteinase and tnf liberation and their therapeutic uses |
US5665777A (en) * | 1995-11-14 | 1997-09-09 | Abbott Laboratories | Biphenyl hydroxamate inhibitors of matrix metalloproteinases |
ATE262899T1 (de) * | 1996-01-02 | 2004-04-15 | Aventis Pharma Inc | Substituierte (aryl, heteroaryl, arylmethyl oder heteroarylmethyl) hydroxamisaeureverbindungen |
-
1998
- 1998-02-17 JP JP53770698A patent/JP2001519777A/ja not_active Withdrawn
- 1998-02-17 HU HU0002092A patent/HUP0002092A3/hu unknown
- 1998-02-17 ES ES98910022T patent/ES2212274T3/es not_active Expired - Lifetime
- 1998-02-17 HU HU0001463A patent/HUP0001463A3/hu unknown
- 1998-02-17 EA EA199900768A patent/EA003836B1/ru not_active IP Right Cessation
- 1998-02-17 GE GEAP19985007A patent/GEP20022627B/en unknown
- 1998-02-17 ES ES98906468T patent/ES2217540T3/es not_active Expired - Lifetime
- 1998-02-17 DE DE69820424T patent/DE69820424T2/de not_active Expired - Fee Related
- 1998-02-17 WO PCT/US1998/002987 patent/WO1998037877A1/en not_active Application Discontinuation
- 1998-02-17 CA CA002282656A patent/CA2282656A1/en not_active Abandoned
- 1998-02-17 YU YU41099A patent/YU41099A/sh unknown
- 1998-02-17 PT PT98906468T patent/PT973512E/pt unknown
- 1998-02-17 NZ NZ337336A patent/NZ337336A/en unknown
- 1998-02-17 PL PL98335401A patent/PL335401A1/xx unknown
- 1998-02-17 TR TR1999/02095T patent/TR199902095T2/xx unknown
- 1998-02-17 AT AT98910022T patent/ATE256107T1/de not_active IP Right Cessation
- 1998-02-17 SK SK1158-99A patent/SK115899A3/sk unknown
- 1998-02-17 JP JP53772498A patent/JP2001513771A/ja not_active Withdrawn
- 1998-02-17 EP EP98906468A patent/EP0973512B1/en not_active Expired - Lifetime
- 1998-02-17 GE GEAP19985008A patent/GEP20022626B/en unknown
- 1998-02-17 EA EA199900769A patent/EA001742B1/ru not_active IP Right Cessation
- 1998-02-17 CN CN98804329A patent/CN1252790A/zh active Pending
- 1998-02-17 TR TR1999/01901T patent/TR199901901T2/xx unknown
- 1998-02-17 DE DE69823019T patent/DE69823019T2/de not_active Expired - Fee Related
- 1998-02-17 KR KR1019997007881A patent/KR20000075808A/ko not_active Application Discontinuation
- 1998-02-17 YU YU40999A patent/YU40999A/sh unknown
- 1998-02-17 EE EEP199900369A patent/EE04150B1/xx not_active IP Right Cessation
- 1998-02-17 EP EP98910022A patent/EP0970046B1/en not_active Expired - Lifetime
- 1998-02-17 BR BR9807803-8A patent/BR9807803A/pt not_active IP Right Cessation
- 1998-02-17 UA UA99095311A patent/UA58543C2/uk unknown
- 1998-02-17 CN CNB988043335A patent/CN1210263C/zh not_active Expired - Fee Related
- 1998-02-17 IL IL13125798A patent/IL131257A0/xx unknown
- 1998-02-17 PL PL98335286A patent/PL335286A1/xx unknown
- 1998-02-17 DK DK98906468T patent/DK0973512T3/da active
- 1998-02-17 BR BR9807802A patent/BR9807802A/pt not_active IP Right Cessation
- 1998-02-17 PT PT98910022T patent/PT970046E/pt unknown
- 1998-02-17 CA CA002282655A patent/CA2282655A1/en not_active Abandoned
- 1998-02-17 NZ NZ337298A patent/NZ337298A/xx unknown
- 1998-02-17 IL IL13125898A patent/IL131258A0/xx not_active IP Right Cessation
- 1998-02-17 WO PCT/US1998/003291 patent/WO1998038163A1/en not_active Application Discontinuation
- 1998-02-17 AU AU64368/98A patent/AU748998B2/en not_active Ceased
- 1998-02-17 SK SK1157-99A patent/SK115799A3/sk unknown
- 1998-02-17 AU AU61686/98A patent/AU726204B2/en not_active Ceased
- 1998-02-17 EE EEP199900371A patent/EE04295B1/xx not_active IP Right Cessation
- 1998-02-17 KR KR1019997007882A patent/KR20000075809A/ko not_active Application Discontinuation
- 1998-02-17 AT AT98906468T patent/ATE263554T1/de not_active IP Right Cessation
- 1998-02-17 DK DK98910022T patent/DK0970046T3/da active
- 1998-02-26 ZA ZA9801625A patent/ZA981625B/xx unknown
- 1998-02-26 ZA ZA9801628A patent/ZA981628B/xx unknown
- 1998-02-27 AR ARP980100909A patent/AR011451A1/es not_active Application Discontinuation
- 1998-03-17 TW TW087102853A patent/TW568900B/zh active
-
1999
- 1999-08-26 NO NO19994125A patent/NO314302B1/no unknown
- 1999-08-26 NO NO19994124A patent/NO314258B1/no not_active IP Right Cessation
- 1999-09-24 BG BG103757A patent/BG103757A/bg unknown
- 1999-09-27 BG BG103760A patent/BG103760A/bg unknown
-
2000
- 2000-07-07 HK HK00104181A patent/HK1024875A1/xx not_active IP Right Cessation
-
2004
- 2004-09-08 CY CY0400069A patent/CY2477B1/xx unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO314302B1 (no) | Matriksmetalloproteinase-inhibitorer, anvendelse derav samt farmasöytisk blanding | |
US6462073B2 (en) | N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors | |
US20030171400A1 (en) | Heterocyclic side chain containing metalloprotease inhibitors | |
CA2320469A1 (en) | N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted-alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors | |
US6358980B1 (en) | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors | |
AU3711800A (en) | Dihetero-substituted metalloprotease inhibitors | |
EP1265864A1 (en) | Heterocyclic side chain containing, n-substituted metalloprotease inhibitors | |
CZ20012707A3 (cs) | Deriváty kyseliny hydroxamové obsahující alkynylovou skupinu jako inhibitory TACE | |
US6753337B2 (en) | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors | |
NZ517983A (en) | Beta disubstituted metalloprotease inhibitors | |
AU769418B2 (en) | Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (MMP) inhibitors/TNF-alpha converting enzyme (TACE) inhibitors | |
CZ20003036A3 (cs) | Inhibitory metaloproteinázy matrice |