NO317760B1 - Heterosykliske substituerte pyrrolidinamidderivater, farmasoytiske preparater som omfatter disse, samt anvendelse av forbindelsene til fremstilling av preparatene - Google Patents

Heterosykliske substituerte pyrrolidinamidderivater, farmasoytiske preparater som omfatter disse, samt anvendelse av forbindelsene til fremstilling av preparatene Download PDF

Info

Publication number: NO317760B1
Authority: NO; Norway
Prior art keywords: pyrrolidine; mmol; methoxy; ethyl; tetrazol
Prior art date: 1996-12-19

Application number

NO19993013A

Other languages

English (en)

Norwegian (no)

Other versions

NO993013D0 (no

NO993013L (no

Inventor

George D Maynard

Timothy Paul Burkholder

Elizabeth Mary Kudlacz

Original Assignee

Aventis Pharma Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-12-19

Filing date

1999-06-18

Publication date

2004-12-13

1999-06-18 Application filed by Aventis Pharma Inc filed Critical Aventis Pharma Inc

1999-06-18 Publication of NO993013D0 publication Critical patent/NO993013D0/no

1999-08-18 Publication of NO993013L publication Critical patent/NO993013L/no

2004-12-13 Publication of NO317760B1 publication Critical patent/NO317760B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 199
238000002360 preparation method Methods 0.000 title description 19
125000000623 heterocyclic group Chemical group 0.000 title description 6
LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical class NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 title description 5
239000008194 pharmaceutical composition Chemical class 0.000 title 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 134
150000003839 salts Chemical class 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 27
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
125000001424 substituent group Chemical group 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 16
238000004519 manufacturing process Methods 0.000 claims description 13
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
239000000825 pharmaceutical preparation Substances 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
206010011224 Cough Diseases 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 5
206010006451 bronchitis Diseases 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 4
208000002193 Pain Diseases 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 255
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 231
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 196
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 143
239000000243 solution Substances 0.000 description 132
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 132
238000006243 chemical reaction Methods 0.000 description 130
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 101
239000011541 reaction mixture Substances 0.000 description 78
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 75
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 75
230000015572 biosynthetic process Effects 0.000 description 74
238000003786 synthesis reaction Methods 0.000 description 74
239000007787 solid Substances 0.000 description 64
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
238000000034 method Methods 0.000 description 62
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 58
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
239000000284 extract Substances 0.000 description 54
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 52
-1 alkyl radical Chemical class 0.000 description 52
239000012044 organic layer Substances 0.000 description 52
239000000741 silica gel Substances 0.000 description 45
229910002027 silica gel Inorganic materials 0.000 description 45
238000010992 reflux Methods 0.000 description 43
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
235000008504 concentrate Nutrition 0.000 description 35
239000012141 concentrate Substances 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
239000002904 solvent Substances 0.000 description 32
238000001914 filtration Methods 0.000 description 30
239000000706 filtrate Substances 0.000 description 29
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
239000002585 base Substances 0.000 description 28
102000003141 Tachykinin Human genes 0.000 description 27
238000004587 chromatography analysis Methods 0.000 description 27
108060008037 tachykinin Proteins 0.000 description 27
238000001953 recrystallisation Methods 0.000 description 26
229920006395 saturated elastomer Polymers 0.000 description 26
238000001704 evaporation Methods 0.000 description 25
230000008020 evaporation Effects 0.000 description 25
238000000605 extraction Methods 0.000 description 25
239000010410 layer Substances 0.000 description 25
239000000047 product Substances 0.000 description 25
235000017557 sodium bicarbonate Nutrition 0.000 description 25
229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
201000010099 disease Diseases 0.000 description 24
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
239000002253 acid Substances 0.000 description 23
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
235000011121 sodium hydroxide Nutrition 0.000 description 21
238000001665 trituration Methods 0.000 description 21
238000003756 stirring Methods 0.000 description 20
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
238000012360 testing method Methods 0.000 description 18
239000011343 solid material Substances 0.000 description 17
NKRLLPCWCPIQPL-UHFFFAOYSA-N 2-pyrrolidin-3-ylethanol Chemical compound OCCC1CCNC1 NKRLLPCWCPIQPL-UHFFFAOYSA-N 0.000 description 16
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 16
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
150000001412 amines Chemical class 0.000 description 16
239000007864 aqueous solution Substances 0.000 description 16
238000000921 elemental analysis Methods 0.000 description 16
108010040722 Neurokinin-2 Receptors Proteins 0.000 description 15
102100037342 Substance-K receptor Human genes 0.000 description 15
150000008064 anhydrides Chemical class 0.000 description 15
239000005557 antagonist Substances 0.000 description 15
238000004128 high performance liquid chromatography Methods 0.000 description 15
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 13
235000011114 ammonium hydroxide Nutrition 0.000 description 13
239000006228 supernatant Substances 0.000 description 13
GGNMTJKRHHLJHH-UHFFFAOYSA-N 3,4,5-trimethoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC(OC)=C1OC GGNMTJKRHHLJHH-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
238000011534 incubation Methods 0.000 description 12
229910000027 potassium carbonate Inorganic materials 0.000 description 12
235000011181 potassium carbonates Nutrition 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
CCIUQRKCMXXTOI-WOJBJXKFSA-N (2r,3r)-2,3-dihydroxy-2,3-bis(4-methoxybenzoyl)butanedioic acid Chemical compound C1=CC(OC)=CC=C1C(=O)[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C(=O)C1=CC=C(OC)C=C1 CCIUQRKCMXXTOI-WOJBJXKFSA-N 0.000 description 11
FDAVBROYKQZBTA-GZJHNZOKSA-N (2r,3r)-2,3-dihydroxy-2,3-bis(4-methoxybenzoyl)butanedioic acid;2-(3-phenylpyrrolidin-3-yl)ethanol Chemical compound C=1C=CC=CC=1C1(CCO)CCNC1.C1=CC(OC)=CC=C1C(=O)[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C(=O)C1=CC=C(OC)C=C1 FDAVBROYKQZBTA-GZJHNZOKSA-N 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
230000027455 binding Effects 0.000 description 11
210000004185 liver Anatomy 0.000 description 11
230000001404 mediated effect Effects 0.000 description 11
239000011734 sodium Substances 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
239000007868 Raney catalyst Substances 0.000 description 10
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 10
229910000564 Raney nickel Inorganic materials 0.000 description 10
239000012267 brine Substances 0.000 description 10
239000000872 buffer Substances 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
WDGFMXWZXUOBQJ-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-yl)benzoyl chloride Chemical compound C1=C(C(Cl)=O)C(OC)=CC=C1N1N=NN=C1 WDGFMXWZXUOBQJ-UHFFFAOYSA-N 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 9
101800000399 Neurokinin A Proteins 0.000 description 9
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235000011054 acetic acid Nutrition 0.000 description 9
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
229910052794 bromium Inorganic materials 0.000 description 9
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 9
239000012467 final product Substances 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
239000012071 phase Substances 0.000 description 9
238000012546 transfer Methods 0.000 description 9
241000700199 Cavia porcellus Species 0.000 description 8
239000012359 Methanesulfonyl chloride Substances 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
230000008485 antagonism Effects 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 8
235000011118 potassium hydroxide Nutrition 0.000 description 8
150000003254 radicals Chemical class 0.000 description 8
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 8
229910000029 sodium carbonate Inorganic materials 0.000 description 8
235000017550 sodium carbonate Nutrition 0.000 description 8
SYIVVGOSXRAAKP-UHFFFAOYSA-N 1-(2-pyrrolidin-3-ylethyl)piperidine Chemical compound C1CNCC1CCN1CCCCC1 SYIVVGOSXRAAKP-UHFFFAOYSA-N 0.000 description 7
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 7
239000000556 agonist Substances 0.000 description 7
125000006242 amine protecting group Chemical group 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
238000001727 in vivo Methods 0.000 description 7
150000002825 nitriles Chemical class 0.000 description 7
239000007858 starting material Substances 0.000 description 7
239000011550 stock solution Substances 0.000 description 7
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 6
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CJMMVDBUGOAMFU-WKTGHYETSA-N 2-[(3S)-3-(3,4-dichlorophenyl)pyrrolidin-3-yl]ethanol (2R,3R)-2,3-dihydroxy-2,3-bis(4-methoxybenzoyl)butanedioic acid Chemical compound C(C1=CC=C(C=C1)OC)(=O)[C@@]([C@@](C(=O)O)(O)C(C1=CC=C(C=C1)OC)=O)(O)C(=O)O.ClC=1C=C(C=CC1Cl)[C@@]1(CNCC1)CCO CJMMVDBUGOAMFU-WKTGHYETSA-N 0.000 description 6
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ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
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102100024304 Protachykinin-1 Human genes 0.000 description 6
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125000003118 aryl group Chemical group 0.000 description 5
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MOLWDHUTJGGDTJ-UHFFFAOYSA-N diethyl 3-cyano-3-(3,4-dichlorophenyl)pentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)(C#N)C1=CC=C(Cl)C(Cl)=C1 MOLWDHUTJGGDTJ-UHFFFAOYSA-N 0.000 description 5
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DDDPTEXHUWWNSY-UHFFFAOYSA-N ethyl 2-(5-oxo-3-phenylpyrrolidin-3-yl)acetate Chemical compound C=1C=CC=CC=1C1(CC(=O)OCC)CNC(=O)C1 DDDPTEXHUWWNSY-UHFFFAOYSA-N 0.000 description 5
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NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000004080 punching Methods 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
238000011002 quantification Methods 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
238000010791 quenching Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
230000001953 sensory effect Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
206010041232 sneezing Diseases 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000001476 sodium potassium tartrate Substances 0.000 description 1
235000011006 sodium potassium tartrate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 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
230000000707 stereoselective effect Effects 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
VDCUDAHEHZLEBF-QGZVFWFLSA-N tert-butyl (3s)-3-(3,4-dichlorophenyl)-3-(2-hydroxyethyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@]1(CCO)C1=CC=C(Cl)C(Cl)=C1 VDCUDAHEHZLEBF-QGZVFWFLSA-N 0.000 description 1
MHCQHDBXYXFCJS-GOSISDBHSA-N tert-butyl (3s)-3-(3,4-dichlorophenyl)-3-(2-methylsulfonyloxyethyl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@]1(CCOS(C)(=O)=O)C1=CC=C(Cl)C(Cl)=C1 MHCQHDBXYXFCJS-GOSISDBHSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 description 1
ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
150000003628 tricarboxylic acids Chemical class 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
MBXYEKQOJQZLHR-UHFFFAOYSA-M triethyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CC)(CC)CC MBXYEKQOJQZLHR-UHFFFAOYSA-M 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
239000008243 triphasic system Substances 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000000264 venule Anatomy 0.000 description 1
201000005539 vernal conjunctivitis Diseases 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

NO19993013A 1996-12-19 1999-06-18 Heterosykliske substituerte pyrrolidinamidderivater, farmasoytiske preparater som omfatter disse, samt anvendelse av forbindelsene til fremstilling av preparatene NO317760B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US76981296A	1996-12-19	1996-12-19
PCT/US1997/019884 WO1998027086A1 (fr)	1996-12-19	1997-11-03	Nouveaux amides derives de la pyrrolidine, a substituant heterocyclique

Publications (3)

Publication Number	Publication Date
NO993013D0 NO993013D0 (no)	1999-06-18
NO993013L NO993013L (no)	1999-08-18
NO317760B1 true NO317760B1 (no)	2004-12-13

Family

ID=25086573

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19993013A NO317760B1 (no)	1996-12-19	1999-06-18	Heterosykliske substituerte pyrrolidinamidderivater, farmasoytiske preparater som omfatter disse, samt anvendelse av forbindelsene til fremstilling av preparatene

Country Status (21)

Country	Link
EP (1)	EP0946548B1 (fr)
JP (1)	JP4195512B2 (fr)
KR (1)	KR100514263B1 (fr)
CN (1)	CN1119344C (fr)
AR (1)	AR009665A1 (fr)
AT (1)	ATE214063T1 (fr)
AU (1)	AU723966B2 (fr)
BR (1)	BR9714057A (fr)
CA (1)	CA2275527C (fr)
DE (1)	DE69710921T2 (fr)
DK (1)	DK0946548T3 (fr)
ES (1)	ES2169881T3 (fr)
HK (1)	HK1020947A1 (fr)
HU (1)	HUP0000315A3 (fr)
IL (1)	IL130223A (fr)
NO (1)	NO317760B1 (fr)
NZ (1)	NZ335975A (fr)
PT (1)	PT946548E (fr)
TW (1)	TW486477B (fr)
WO (1)	WO1998027086A1 (fr)
ZA (1)	ZA9711271B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ID29137A (id) *	1998-07-27	2001-08-02	Schering Corp	Ligan-ligan afinitas tinggi untuk reseptor nosiseptin orl-1
CN1529600A (zh) *	2001-07-20	2004-09-15	�Ʒ�	Nk-1受体拮抗剂在改变狗、猫和马的不需要行为中的用途
RU2010108687A (ru)	2007-08-22	2011-09-27	Ф.Хоффманн-Ля Рош Аг (Ch)	Ариловые эфиры пирролидина в качестве антагонистов рецепторов nk3
JP7425793B2 (ja)	2018-10-29	2024-01-31	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	ピリジニルスルホンアミド誘導体、医薬組成物およびそれらの使用
AU2019373306B2 (en)	2018-10-29	2024-10-10	Boehringer Ingelheim International Gmbh	Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2676055B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Composes polycycliques amines et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
CN1081635C (zh) *	1993-05-06	2002-03-27	默里尔药物公司	取代的吡咯烷－3－基－烷基－哌啶
HUP9900927A3 (en) *	1995-11-17	2002-02-28	Aventis Pharmaceuticals Inc Br	Substituted 4-(1h-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases

1997
- 1997-11-03 HU HU0000315A patent/HUP0000315A3/hu unknown
- 1997-11-03 ES ES97946443T patent/ES2169881T3/es not_active Expired - Lifetime
- 1997-11-03 DE DE69710921T patent/DE69710921T2/de not_active Expired - Lifetime
- 1997-11-03 PT PT97946443T patent/PT946548E/pt unknown
- 1997-11-03 JP JP52768298A patent/JP4195512B2/ja not_active Expired - Lifetime
- 1997-11-03 DK DK97946443T patent/DK0946548T3/da active
- 1997-11-03 AU AU51607/98A patent/AU723966B2/en not_active Ceased
- 1997-11-03 CA CA002275527A patent/CA2275527C/fr not_active Expired - Fee Related
- 1997-11-03 WO PCT/US1997/019884 patent/WO1998027086A1/fr active IP Right Grant
- 1997-11-03 CN CN97180825A patent/CN1119344C/zh not_active Expired - Fee Related
- 1997-11-03 BR BR9714057-0A patent/BR9714057A/pt not_active Application Discontinuation
- 1997-11-03 IL IL13022397A patent/IL130223A/xx not_active IP Right Cessation
- 1997-11-03 AT AT97946443T patent/ATE214063T1/de not_active IP Right Cessation
- 1997-11-03 KR KR10-1999-7005496A patent/KR100514263B1/ko not_active IP Right Cessation
- 1997-11-03 NZ NZ335975A patent/NZ335975A/xx unknown
- 1997-11-03 EP EP97946443A patent/EP0946548B1/fr not_active Expired - Lifetime
- 1997-12-15 ZA ZA9711271A patent/ZA9711271B/xx unknown
- 1997-12-16 TW TW086119004A patent/TW486477B/zh not_active IP Right Cessation
- 1997-12-17 AR ARP970105923A patent/AR009665A1/es active IP Right Grant
1999
- 1999-06-18 NO NO19993013A patent/NO317760B1/no unknown
- 1999-12-21 HK HK99106022A patent/HK1020947A1/xx unknown

Also Published As

Publication number	Publication date
NZ335975A (en)	2000-11-24
DK0946548T3 (da)	2002-06-24
NO993013D0 (no)	1999-06-18
KR20000057668A (ko)	2000-09-25
WO1998027086A1 (fr)	1998-06-25
EP0946548B1 (fr)	2002-03-06
AU5160798A (en)	1998-07-15
CA2275527A1 (fr)	1998-06-25
PT946548E (pt)	2002-06-28
HUP0000315A2 (hu)	2001-04-28
DE69710921D1 (de)	2002-04-11
CN1241185A (zh)	2000-01-12
AU723966B2 (en)	2000-09-07
DE69710921T2 (de)	2002-09-19
IL130223A (en)	2005-09-25
IL130223A0 (en)	2000-06-01
HUP0000315A3 (en)	2002-01-28
JP2001506650A (ja)	2001-05-22
ES2169881T3 (es)	2002-07-16
ZA9711271B (en)	1998-06-19
HK1020947A1 (en)	2000-05-26
AR009665A1 (es)	2000-04-26
NO993013L (no)	1999-08-18
CA2275527C (fr)	2003-09-23
ATE214063T1 (de)	2002-03-15
TW486477B (en)	2002-05-11
BR9714057A (pt)	2000-05-09
JP4195512B2 (ja)	2008-12-10
KR100514263B1 (ko)	2005-09-15
EP0946548A1 (fr)	1999-10-06
CN1119344C (zh)	2003-08-27

Publication	Publication Date	Title
NO309144B1 (no)	2000-12-18	Substituerte pyrrolidin-3-yl-alkyl-piperidiner som er anvendbare som tachykininantagonister
EP0946545B1 (fr)	2001-09-05	Nouveaux derives carboxamides cycliques substitues par carboxy
US5861417A (en)	1999-01-19	Heterocyclic substituted pyrrolidine amide derivatives
NO317760B1 (no)	2004-12-13	Heterosykliske substituerte pyrrolidinamidderivater, farmasoytiske preparater som omfatter disse, samt anvendelse av forbindelsene til fremstilling av preparatene
EP0815105B1 (fr)	2001-10-04	Derives de piperazinone substitues par un heterocycle agissant comme antagonistes du recepteur de tachykinine
US6316445B1 (en)	2001-11-13	Carboxy substituted acylic carboxamide derivatives
EP1077942B1 (fr)	2005-01-12	Derives carboxamides a substitution carboxy utilises comme antagonistes du recepteur de la tachykinine
US5977139A (en)	1999-11-02	Carboxysubstituted cyclic carboxamide derivatives
CA2329075C (fr)	2005-10-18	Derives carboxamides a substitution carboxy utilises comme antagonistes du recepteur de la tachykinine
MXPA99005744A (en)	2000-01-21	Novel heterocyclic substituted pyrrolidine amide derivatives
CZ223999A3 (cs)	2000-01-12	Karboxy-substituované cyklické karboxamidové deriváty, farmaceutické prostředky obsahující tyto sloučeniny a použití těchto sloučenin