HRP20000310A2 - New dibenzoazulene compounds as tumor necrosis factor inhibitors - Google Patents

New dibenzoazulene compounds as tumor necrosis factor inhibitors Download PDF

Info

Publication number: HRP20000310A2
Authority: HR; Croatia
Prior art keywords: dibenzo; azulen; ylmethoxy; ethyl; dithia
Prior art date: 2000-05-17

Application number

HR20000310A

Other languages

English (en)

Croatian (hr)

Inventor

Merćep Mladen

Mesić Milan

Peueić Dijana

Aeupanović Aeeljko

Hrvačić Boueka

Original Assignee

Pliva Farmaceutska Ind Dioniko

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.)

2000-05-17

Filing date

2000-05-17

Publication date

2002-02-28

2000-05-17 Application filed by Pliva Farmaceutska Ind Dioniko filed Critical Pliva Farmaceutska Ind Dioniko

2000-05-17 Priority to HR20000310A priority Critical patent/HRP20000310A2/hr

2001-05-16 Priority to AU2001256560A priority patent/AU2001256560B2/en

2001-05-16 Priority to YUP-841/02A priority patent/RS50893B/sr

2001-05-16 Priority to AU5656001A priority patent/AU5656001A/xx

2001-05-16 Priority to BR0111202-3A priority patent/BR0111202A/pt

2001-05-16 Priority to EP01929882A priority patent/EP1284977B1/en

2001-05-16 Priority to IL15280901A priority patent/IL152809A0/xx

2001-05-16 Priority to PT01929882T priority patent/PT1284977E/pt

2001-05-16 Priority to EEP200200636A priority patent/EE200200636A/xx

2001-05-16 Priority to HU0302295A priority patent/HUP0302295A3/hu

2001-05-16 Priority to AT01929882T priority patent/ATE434619T1/de

2001-05-16 Priority to PL365054A priority patent/PL204849B1/pl

2001-05-16 Priority to GE5019A priority patent/GEP20043304B/en

2001-05-16 Priority to DZ013357A priority patent/DZ3357A1/fr

2001-05-16 Priority to SK1770-2002A priority patent/SK17702002A3/sk

2001-05-16 Priority to NZ522553A priority patent/NZ522553A/en

2001-05-16 Priority to CA2409090A priority patent/CA2409090C/en

2001-05-16 Priority to CNB018115896A priority patent/CN1194976C/zh

2001-05-16 Priority to ES01929882T priority patent/ES2328335T3/es

2001-05-16 Priority to JP2001584284A priority patent/JP2003533528A/ja

2001-05-16 Priority to CZ20024090A priority patent/CZ301770B6/cs

2001-05-16 Priority to DE60139070T priority patent/DE60139070D1/de

2001-05-16 Priority to EA200201223A priority patent/EA006069B1/ru

2001-05-16 Priority to PCT/HR2001/000027 priority patent/WO2001087890A1/en

2001-05-16 Priority to SI200130930T priority patent/SI1284977T1/sl

2001-05-16 Priority to MXPA02011269A priority patent/MXPA02011269A/es

2001-05-16 Priority to DK01929882T priority patent/DK1284977T3/da

2001-05-16 Priority to KR1020027015567A priority patent/KR100823064B1/ko

2001-05-17 Priority to ARP010102339A priority patent/AR030562A1/es

2002-02-28 Publication of HRP20000310A2 publication Critical patent/HRP20000310A2/hr

2002-11-11 Priority to MA26901A priority patent/MA27125A1/fr

2002-11-12 Priority to ZA200209180A priority patent/ZA200209180B/en

2002-11-14 Priority to IS6621A priority patent/IS6621A/is

2002-11-15 Priority to NO20025510A priority patent/NO20025510L/no

2002-11-18 Priority to US10/298,217 priority patent/US6897211B2/en

2002-12-17 Priority to CR6860A priority patent/CR6860A/es

2002-12-17 Priority to BG107399A priority patent/BG65967B1/bg

2003-12-11 Priority to HK03109004A priority patent/HK1056719A1/xx

2005-03-25 Priority to US11/090,743 priority patent/US20050171091A1/en

2009-08-20 Priority to CY20091100888T priority patent/CY1109328T1/el

Links

150000001875 compounds Chemical class 0.000 title claims description 62
229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 title description 2
239000002451 tumor necrosis factor inhibitor Substances 0.000 title description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 98
238000006243 chemical reaction Methods 0.000 claims description 63
-1 cyano, amino Chemical group 0.000 claims description 54
YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 53
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
238000000034 method Methods 0.000 claims description 31
239000011541 reaction mixture Substances 0.000 claims description 28
238000004440 column chromatography Methods 0.000 claims description 25
238000010992 reflux Methods 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 22
238000000746 purification Methods 0.000 claims description 21
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
238000002360 preparation method Methods 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 11
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
238000002955 isolation Methods 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
239000000741 silica gel Substances 0.000 claims description 8
229910002027 silica gel Inorganic materials 0.000 claims description 8
239000003112 inhibitor Substances 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
238000001953 recrystallisation Methods 0.000 claims description 7
102000004127 Cytokines Human genes 0.000 claims description 6
108090000695 Cytokines Proteins 0.000 claims description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
230000001575 pathological effect Effects 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
206010061218 Inflammation Diseases 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000004414 alkyl thio group Chemical group 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
238000004587 chromatography analysis Methods 0.000 claims description 5
230000004054 inflammatory process Effects 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
150000001298 alcohols Chemical class 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
JTXULCJEMDHNBH-UHFFFAOYSA-N C12=CC=C(Cl)C=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 Chemical compound C12=CC=C(Cl)C=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 JTXULCJEMDHNBH-UHFFFAOYSA-N 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
238000001914 filtration Methods 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
239000002609 medium Substances 0.000 claims description 3
238000011321 prophylaxis Methods 0.000 claims description 3
239000012453 solvate Substances 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 2
RNHSJWDRJGCMOR-UHFFFAOYSA-N C12=CC(F)=CC=C2OC2=CC=CC=C2C2=C1SC(CCC(=O)O)=C2 Chemical compound C12=CC(F)=CC=C2OC2=CC=CC=C2C2=C1SC(CCC(=O)O)=C2 RNHSJWDRJGCMOR-UHFFFAOYSA-N 0.000 claims description 2
QIZJVNKFGXAYPR-UHFFFAOYSA-N Cl.C12=CC=C(Br)C=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 Chemical compound Cl.C12=CC=C(Br)C=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 QIZJVNKFGXAYPR-UHFFFAOYSA-N 0.000 claims description 2
RZGJWVFLDKZTTI-UHFFFAOYSA-L Cl[Cr](=O)(=O)OC1=CC=CC=N1 Chemical compound Cl[Cr](=O)(=O)OC1=CC=CC=N1 RZGJWVFLDKZTTI-UHFFFAOYSA-L 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
101150020251 NR13 gene Proteins 0.000 claims description 2
RHHSGLPWDHEVIR-UHFFFAOYSA-L O[Cr](O[Cr](OC1=CC=CC=N1)(=O)=O)(=O)=O Chemical compound O[Cr](O[Cr](OC1=CC=CC=N1)(=O)=O)(=O)=O RHHSGLPWDHEVIR-UHFFFAOYSA-L 0.000 claims description 2
150000003973 alkyl amines Chemical class 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000005907 alkyl ester group Chemical group 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
150000008064 anhydrides Chemical class 0.000 claims description 2
150000007860 aryl ester derivatives Chemical class 0.000 claims description 2
CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
239000003054 catalyst Substances 0.000 claims description 2
125000001188 haloalkyl group Chemical group 0.000 claims description 2
125000004970 halomethyl group Chemical group 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
231100000252 nontoxic Toxicity 0.000 claims description 2
230000003000 nontoxic effect Effects 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052763 palladium Inorganic materials 0.000 claims description 2
238000003408 phase transfer catalysis Methods 0.000 claims description 2
239000003444 phase transfer catalyst Substances 0.000 claims description 2
238000012545 processing Methods 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
150000003254 radicals Chemical class 0.000 claims 12
239000003153 chemical reaction reagent Substances 0.000 claims 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 claims 1
238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
150000004678 hydrides Chemical class 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
239000012454 non-polar solvent Substances 0.000 claims 1
239000003960 organic solvent Substances 0.000 claims 1
230000020477 pH reduction Effects 0.000 claims 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
229910052703 rhodium Inorganic materials 0.000 claims 1
239000010948 rhodium Substances 0.000 claims 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims 1
239000000377 silicon dioxide Substances 0.000 claims 1
239000000047 product Substances 0.000 description 76
238000005160 1H NMR spectroscopy Methods 0.000 description 64
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 64
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
239000000243 solution Substances 0.000 description 42
102100040247 Tumor necrosis factor Human genes 0.000 description 35
108060008682 Tumor Necrosis Factor Proteins 0.000 description 29
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 24
108010002352 Interleukin-1 Proteins 0.000 description 24
102000000589 Interleukin-1 Human genes 0.000 description 24
239000002158 endotoxin Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
229920006008 lipopolysaccharide Polymers 0.000 description 16
230000028327 secretion Effects 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 14
LJQNMDZRCXJETK-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CN(C)CCCCl LJQNMDZRCXJETK-UHFFFAOYSA-N 0.000 description 14
210000004027 cell Anatomy 0.000 description 14
238000003756 stirring Methods 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical group [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
230000005764 inhibitory process Effects 0.000 description 12
VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 11
206010039073 rheumatoid arthritis Diseases 0.000 description 11
241001465754 Metazoa Species 0.000 description 10
238000012360 testing method Methods 0.000 description 10
FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
239000000126 substance Substances 0.000 description 9
NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
229910052799 carbon Inorganic materials 0.000 description 7
230000006433 tumor necrosis factor production Effects 0.000 description 7
GXMSLNZIHPZWAI-UHFFFAOYSA-N 5-thiatetracyclo[12.4.0.02,6.08,13]octadeca-1(18),2,6,8,10,12,14,16-octaene Chemical class S1CC=C2C3=C(C4=C(C=C12)C=CC=C4)C=CC=C3 GXMSLNZIHPZWAI-UHFFFAOYSA-N 0.000 description 6
238000002965 ELISA Methods 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000003814 drug Substances 0.000 description 6
241000699666 Mus <mouse, genus> Species 0.000 description 5
230000000202 analgesic effect Effects 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
238000000160 carbon, hydrogen and nitrogen elemental analysis Methods 0.000 description 4
125000000753 cycloalkyl group Chemical group 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
230000002757 inflammatory effect Effects 0.000 description 4
230000018276 interleukin-1 production Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
108010008165 Etanercept Proteins 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
239000012980 RPMI-1640 medium Substances 0.000 description 3
230000009471 action Effects 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000013642 negative control Substances 0.000 description 3
210000003024 peritoneal macrophage Anatomy 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000013641 positive control Substances 0.000 description 3
230000008054 signal transmission Effects 0.000 description 3
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
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 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010009900 Colitis ulcerative Diseases 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 2
102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
201000006704 Ulcerative Colitis Diseases 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
230000002917 arthritic effect Effects 0.000 description 2
238000003556 assay Methods 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
229960000598 infliximab Drugs 0.000 description 2
230000002401 inhibitory effect Effects 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
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
229960002900 methylcellulose Drugs 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
230000004963 pathophysiological condition Effects 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
210000003200 peritoneal cavity Anatomy 0.000 description 2
RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
239000000651 prodrug Chemical group 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
230000035939 shock Effects 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
KAANTNXREIRLCT-UHFFFAOYSA-N 1-(triphenyl-$l^{5}-phosphanylidene)propan-2-one Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)C)C1=CC=CC=C1 KAANTNXREIRLCT-UHFFFAOYSA-N 0.000 description 1
WNSVNBQGIRRNLR-UHFFFAOYSA-N 1-[2-(13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),2(6),4,7,9,11,14,16-octaen-4-ylmethoxy)ethyl]piperidine hydrochloride Chemical compound Cl.C=1C(C2=CC=CC=C2OC2=CC=CC=C22)=C2SC=1COCCN1CCCCC1 WNSVNBQGIRRNLR-UHFFFAOYSA-N 0.000 description 1
SQNXZINOQZHERU-UHFFFAOYSA-N 1-[2-(13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),2(6),4,7,9,11,14,16-octaen-4-ylmethoxy)ethyl]pyrrolidine hydrochloride Chemical compound Cl.C=1C(C2=CC=CC=C2OC2=CC=CC=C22)=C2SC=1COCCN1CCCC1 SQNXZINOQZHERU-UHFFFAOYSA-N 0.000 description 1
POXOJRBFXVLJJG-UHFFFAOYSA-N 1-[2-[[16-(trifluoromethyl)-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl]methoxy]ethyl]pyrrolidine hydrochloride Chemical compound Cl.C=1C=2C3=CC=CC=C3SC3=CC(C(F)(F)F)=CC=C3C=2SC=1COCCN1CCCC1 POXOJRBFXVLJJG-UHFFFAOYSA-N 0.000 description 1
SSGLEOCDWJFZPE-UHFFFAOYSA-N 2-[(17-fluoro-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]-N,N-dimethylethanamine hydrochloride Chemical compound Cl.C12=CC(F)=CC=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 SSGLEOCDWJFZPE-UHFFFAOYSA-N 0.000 description 1
OCWGRWAYARCRTQ-UHFFFAOYSA-N 2-chloro-n,n-dimethylpropan-1-amine;hydron;chloride Chemical compound Cl.CC(Cl)CN(C)C OCWGRWAYARCRTQ-UHFFFAOYSA-N 0.000 description 1
WZGUWRZWSVYUGA-UHFFFAOYSA-N 3-(17-fluoro-13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)prop-2-enoic acid Chemical compound C12=CC(F)=CC=C2OC2=CC=CC=C2C2=C1SC(C=CC(=O)O)=C2 WZGUWRZWSVYUGA-UHFFFAOYSA-N 0.000 description 1
MJWIOSFQVSLWCV-UHFFFAOYSA-N 3-[(15,17-dimethyl-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),2(6),4,7,9,11,14,16-octaen-4-yl)methoxy]-N,N-dimethylpropan-1-amine hydrochloride Chemical compound Cl.C12=CC(C)=CC(C)=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 MJWIOSFQVSLWCV-UHFFFAOYSA-N 0.000 description 1
NMBGCBJQNLIVPD-UHFFFAOYSA-N 3-[(15-chloro-13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]-N,N-dimethylpropan-1-amine Chemical compound C12=CC=CC(Cl)=C2OC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 NMBGCBJQNLIVPD-UHFFFAOYSA-N 0.000 description 1
PXCXNYYBFSAIKL-UHFFFAOYSA-N 3-[(15-chloro-17-fluoro-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]-N,N-dimethylpropan-1-amine hydrochloride Chemical compound Cl.C12=CC(F)=CC(Cl)=C2SC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 PXCXNYYBFSAIKL-UHFFFAOYSA-N 0.000 description 1
HROMICXIICYESN-UHFFFAOYSA-N 4-(17-chloro-13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)but-3-en-2-one Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2C2=C1SC(C=CC(=O)C)=C2 HROMICXIICYESN-UHFFFAOYSA-N 0.000 description 1
LSLDGAZGQWNMFR-UHFFFAOYSA-N 4-(17-fluoro-13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)but-3-en-2-one Chemical compound C12=CC(F)=CC=C2OC2=CC=CC=C2C2=C1SC(C=CC(=O)C)=C2 LSLDGAZGQWNMFR-UHFFFAOYSA-N 0.000 description 1
MZDXSRNKEWMDCM-UHFFFAOYSA-N 4-[2-(13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),2(6),4,7,9,11,14,16-octaen-4-ylmethoxy)ethyl]morpholine hydrochloride Chemical compound Cl.C=1C(C2=CC=CC=C2OC2=CC=CC=C22)=C2SC=1COCCN1CCOCC1 MZDXSRNKEWMDCM-UHFFFAOYSA-N 0.000 description 1
IMIOAEASDNIJFA-UHFFFAOYSA-N 4-[2-[(17-bromo-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]ethyl]morpholine Chemical compound S1C=2C3=CC(Br)=CC=C3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 IMIOAEASDNIJFA-UHFFFAOYSA-N 0.000 description 1
ODQNCXWUCFPGSW-UHFFFAOYSA-N 4-[2-[(17-fluoro-13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]ethyl]morpholine hydrochloride Chemical compound Cl.S1C=2C3=CC(F)=CC=C3OC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 ODQNCXWUCFPGSW-UHFFFAOYSA-N 0.000 description 1
BRIQGBRVLIIVKY-UHFFFAOYSA-N 4-[2-[(17-fluoro-3,13-dithiatetracyclo[12.4.0.02,6.07,12]octadeca-1(14),2(6),4,7,9,11,15,17-octaen-4-yl)methoxy]ethyl]morpholine hydrochloride Chemical compound Cl.S1C=2C3=CC(F)=CC=C3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 BRIQGBRVLIIVKY-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229920001817 Agar Polymers 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
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
LXOIYMFFJOSPIF-UHFFFAOYSA-N C12=CC(Cl)=CC=C2OC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2C2=C1SC(COCCCN(C)C)=C2 LXOIYMFFJOSPIF-UHFFFAOYSA-N 0.000 description 1
IDFAGQUZTTZUDL-UHFFFAOYSA-N C=1C=2C3=CC=CC=C3OC=3C(Cl)=CC=CC=3C=2SC=1COCCN1CCOCC1 Chemical compound C=1C=2C3=CC=CC=C3OC=3C(Cl)=CC=CC=3C=2SC=1COCCN1CCOCC1 IDFAGQUZTTZUDL-UHFFFAOYSA-N 0.000 description 1
206010006895 Cachexia Diseases 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
BIIWZXUFHNODJC-UHFFFAOYSA-N Cl.C12=CC(Br)=CC=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 Chemical compound Cl.C12=CC(Br)=CC=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 BIIWZXUFHNODJC-UHFFFAOYSA-N 0.000 description 1
PFQZUHVVDDOURF-UHFFFAOYSA-N Cl.C12=CC(Cl)=CC=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 Chemical compound Cl.C12=CC(Cl)=CC=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 PFQZUHVVDDOURF-UHFFFAOYSA-N 0.000 description 1
GIUDILHULCTFCL-UHFFFAOYSA-N Cl.C12=CC=C(C(F)(F)F)C=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 Chemical compound Cl.C12=CC=C(C(F)(F)F)C=C2SC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 GIUDILHULCTFCL-UHFFFAOYSA-N 0.000 description 1
HKPWVLDQXASOFI-UHFFFAOYSA-N Cl.C=1C(C2=CC=CC=C2SC2=CC=CC=C22)=C2SC=1COCCN1CCOCC1 Chemical compound Cl.C=1C(C2=CC=CC=C2SC2=CC=CC=C22)=C2SC=1COCCN1CCOCC1 HKPWVLDQXASOFI-UHFFFAOYSA-N 0.000 description 1
AHUVELRDDLRYMA-UHFFFAOYSA-N Cl.S1C=2C3=CC(Cl)=CC=C3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 Chemical compound Cl.S1C=2C3=CC(Cl)=CC=C3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 AHUVELRDDLRYMA-UHFFFAOYSA-N 0.000 description 1
TUDMUUAEEMBKKM-UHFFFAOYSA-N Cl.S1C=2C=3C=C(Cl)C(Cl)=CC=3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 Chemical compound Cl.S1C=2C=3C=C(Cl)C(Cl)=CC=3SC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 TUDMUUAEEMBKKM-UHFFFAOYSA-N 0.000 description 1
102000029816 Collagenase Human genes 0.000 description 1
108060005980 Collagenase Proteins 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
108010036949 Cyclosporine Proteins 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010018364 Glomerulonephritis Diseases 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
244000020551 Helianthus annuus Species 0.000 description 1
101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
206010022489 Insulin Resistance Diseases 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 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
229910010084 LiAlH4 Inorganic materials 0.000 description 1
WLCXQFOILVGYCV-UHFFFAOYSA-N N,N-dimethyl-2-(13-oxa-3-thiatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),2(6),4,7,9,11,14,16-octaen-4-ylmethoxy)ethanamine hydrochloride Chemical compound Cl.C12=CC=CC=C2OC2=CC=CC=C2C2=C1SC(COCCN(C)C)=C2 WLCXQFOILVGYCV-UHFFFAOYSA-N 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
208000037273 Pathologic Processes Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
206010036030 Polyarthritis Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
241000219061 Rheum Species 0.000 description 1
NMTFQBGBACMSPP-UHFFFAOYSA-N S1C=2C3=CC(Cl)=CC=C3OC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 Chemical compound S1C=2C3=CC(Cl)=CC=C3OC3=CC=CC=C3C=2C=C1COCCN1CCOCC1 NMTFQBGBACMSPP-UHFFFAOYSA-N 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
241000607720 Serratia Species 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
201000002661 Spondylitis Diseases 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
241000906446 Theraps Species 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
206010044248 Toxic shock syndrome Diseases 0.000 description 1
231100000650 Toxic shock syndrome Toxicity 0.000 description 1
206010054094 Tumour necrosis Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
229920000392 Zymosan Polymers 0.000 description 1
KKMXNGLNAMDYPV-UHFFFAOYSA-N [Cl-].C(C1=CC=CC=C1)[NH2+]C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [Cl-].C(C1=CC=CC=C1)[NH2+]C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 KKMXNGLNAMDYPV-UHFFFAOYSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
125000002009 alkene group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
230000009134 cell regulation Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000035605 chemotaxis Effects 0.000 description 1
TWLCEYWYILDCDA-UHFFFAOYSA-N chromium(6+) oxygen(2-) pyridine Chemical compound [O-2].[O-2].[O-2].[Cr+6].C1=CC=NC=C1.C1=CC=NC=C1 TWLCEYWYILDCDA-UHFFFAOYSA-N 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
229960001265 ciclosporin Drugs 0.000 description 1
229960002424 collagenase Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
229940073621 enbrel Drugs 0.000 description 1
229960000403 etanercept Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
150000004677 hydrates Chemical group 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000007365 immunoregulation Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
239000002085 irritant Substances 0.000 description 1
231100000021 irritant Toxicity 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
229960000681 leflunomide Drugs 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229960000485 methotrexate Drugs 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
238000002156 mixing Methods 0.000 description 1
239000000203 mixture Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
238000007344 nucleophilic reaction Methods 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
231100000915 pathological change Toxicity 0.000 description 1
230000036285 pathological change Effects 0.000 description 1
230000009054 pathological process Effects 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
208000005069 pulmonary fibrosis Diseases 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
229940116176 remicade Drugs 0.000 description 1
102220067365 rs143592561 Human genes 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229960001967 tacrolimus Drugs 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
LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
229960003676 tenidap Drugs 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
150000003536 tetrazoles Chemical class 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
150000003577 thiophenes Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000009385 viral infection Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- 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
- 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
- A61P17/00—Drugs for dermatological disorders
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
- A61P35/00—Antineoplastic agents
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Dermatology (AREA)
Immunology (AREA)
Rheumatology (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Ophthalmology & Optometry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

HR20000310A 2000-05-17 2000-05-17 New dibenzoazulene compounds as tumor necrosis factor inhibitors HRP20000310A2 (en)

Priority Applications (39)

Application Number	Priority Date	Filing Date	Title
HR20000310A HRP20000310A2 (en)	2000-05-17	2000-05-17	New dibenzoazulene compounds as tumor necrosis factor inhibitors
CZ20024090A CZ301770B6 (cs)	2000-05-17	2001-05-16	Dibenzoazulenové deriváty jako inhibitory rakovinných nekróz a farmaceutický prostredek je obsahující
JP2001584284A JP2003533528A (ja)	2000-05-17	2001-05-16	腫瘍壊死因子抑制剤としてのチエノベンゾアズレン化合物
AU5656001A AU5656001A (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
BR0111202-3A BR0111202A (pt)	2000-05-17	2001-05-16	Compostos de tienodibenzoazuleno como inibidores do fator de necrose tumoral
EP01929882A EP1284977B1 (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
IL15280901A IL152809A0 (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
PT01929882T PT1284977E (pt)	2000-05-17	2001-05-16	Compostos de tienodibenzoazuleno como inibidores do factor de necrose tumoral
EEP200200636A EE200200636A (et)	2000-05-17	2001-05-16	Dibensoasuleeni derivaadid, nende valmistamismeetodid ja kasutamine
HU0302295A HUP0302295A3 (en)	2000-05-17	2001-05-16	Thienodibenzoazulene derivatives, process for their preparation and use thereof
AT01929882T ATE434619T1 (de)	2000-05-17	2001-05-16	Thienodibenzazulenverbindungen als tumornekrosefaktorhemmer
PL365054A PL204849B1 (pl)	2000-05-17	2001-05-16	Pochodne dibenzoazulenu, sposób ich wytwarzania oraz zastosowanie
GE5019A GEP20043304B (en)	2000-05-17	2001-05-16	Thienodibenzoazulene Compounds as Tumor Necrosis Factor Inhibitors
DZ013357A DZ3357A1 (fr)	2000-05-17	2001-05-16	Nouveaux médicaments composés de dibenzoazulène comme inhibiteurs de facteur onconécrosant
DE60139070T DE60139070D1 (de)	2000-05-17	2001-05-16	Thienodibenzazulenverbindungen als tumornekrosefaktorhemmer
NZ522553A NZ522553A (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
YUP-841/02A RS50893B (sr)	2000-05-17	2001-05-16	Nova dibenzoazulen jedinjenja kao inhibitori faktora nekroze tumora
CNB018115896A CN1194976C (zh)	2000-05-17	2001-05-16	作为肿瘤坏死因子抑制剂的噻吩并二苯并薁化合物
ES01929882T ES2328335T3 (es)	2000-05-17	2001-05-16	Compuestos de tienodibenzoazuleno como inhibidores del factor de necrosis tumoral.
AU2001256560A AU2001256560B2 (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
CA2409090A CA2409090C (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
SK1770-2002A SK17702002A3 (sk)	2000-05-17	2001-05-16	Tienodibenzoazulénové zlúčeniny ako inhibítory rakovinových nekróz
EA200201223A EA006069B1 (ru)	2000-05-17	2001-05-16	Тиенодибензоазуленовые соединения в качестве ингибиторов фактора некроза опухоли
PCT/HR2001/000027 WO2001087890A1 (en)	2000-05-17	2001-05-16	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
SI200130930T SI1284977T1 (sl)	2000-05-17	2001-05-16	Tienodibenzoazulenske spojine kot zaviralci tumorskega nekroznega faktorja
MXPA02011269A MXPA02011269A (es)	2000-05-17	2001-05-16	Compuestos de tienodibenzoazuleno como inhibidores del factor necrosis tumoral.
DK01929882T DK1284977T3 (da)	2000-05-17	2001-05-16	Thienodibenzoazulenforbindelser som tumornekrosefaktorhæmmere
KR1020027015567A KR100823064B1 (ko)	2000-05-17	2001-05-16	종양 괴사 인자 억제제로서의 티에노디벤조아줄렌 화합물
ARP010102339A AR030562A1 (es)	2000-05-17	2001-05-17	Derivados de dibenzoazuleno, su uso y procedimientos para prepararlos.
MA26901A MA27125A1 (fr)	2000-05-17	2002-11-11	Composes de thienodibenzoazulene comme inhibiteurs de facteurs de tumeur de necrose
ZA200209180A ZA200209180B (en)	2000-05-17	2002-11-12	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors.
IS6621A IS6621A (is)	2000-05-17	2002-11-14	Þíenódíbensóasúlen efnasambönd sem hindrar fyrir æxlisdrepþátt
NO20025510A NO20025510L (no)	2000-05-17	2002-11-15	Dibenzoazulen-derivater samt anvendelse derav
US10/298,217 US6897211B2 (en)	2000-05-17	2002-11-18	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
BG107399A BG65967B1 (bg)	2000-05-17	2002-12-17	Тиенодибензоазуленови съединения като инхибитори на туморен некрозен фактор
CR6860A CR6860A (es)	2000-05-17	2002-12-17	Nuevos compuestos de dibenzoazuleno inhibidores del factor a de necrosis tumoral
HK03109004A HK1056719A1 (en)	2000-05-17	2003-12-11	thienodibenzoazulene compounds as tumor necrosis factor inhibitors.
US11/090,743 US20050171091A1 (en)	2000-05-17	2005-03-25	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
CY20091100888T CY1109328T1 (el)	2000-05-17	2009-08-20	Ενωσεις θειενοδιβενζοαζουλενιου ως αναστολεις παραγοντα νεκρωσης ογκου

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
HR20000310A HRP20000310A2 (en)	2000-05-17	2000-05-17	New dibenzoazulene compounds as tumor necrosis factor inhibitors

Publications (1)

Publication Number	Publication Date
HRP20000310A2 true HRP20000310A2 (en)	2002-02-28

Family

ID=10947110

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR20000310A HRP20000310A2 (en)	2000-05-17	2000-05-17	New dibenzoazulene compounds as tumor necrosis factor inhibitors

Country Status (37)

Country	Link
US (2)	US6897211B2 (sh)
EP (1)	EP1284977B1 (sh)
JP (1)	JP2003533528A (sh)
KR (1)	KR100823064B1 (sh)
CN (1)	CN1194976C (sh)
AR (1)	AR030562A1 (sh)
AT (1)	ATE434619T1 (sh)
AU (2)	AU2001256560B2 (sh)
BG (1)	BG65967B1 (sh)
BR (1)	BR0111202A (sh)
CA (1)	CA2409090C (sh)
CR (1)	CR6860A (sh)
CY (1)	CY1109328T1 (sh)
CZ (1)	CZ301770B6 (sh)
DE (1)	DE60139070D1 (sh)
DK (1)	DK1284977T3 (sh)
DZ (1)	DZ3357A1 (sh)
EA (1)	EA006069B1 (sh)
EE (1)	EE200200636A (sh)
ES (1)	ES2328335T3 (sh)
GE (1)	GEP20043304B (sh)
HK (1)	HK1056719A1 (sh)
HR (1)	HRP20000310A2 (sh)
HU (1)	HUP0302295A3 (sh)
IL (1)	IL152809A0 (sh)
IS (1)	IS6621A (sh)
MA (1)	MA27125A1 (sh)
MX (1)	MXPA02011269A (sh)
NO (1)	NO20025510L (sh)
NZ (1)	NZ522553A (sh)
PL (1)	PL204849B1 (sh)
PT (1)	PT1284977E (sh)
RS (1)	RS50893B (sh)
SI (1)	SI1284977T1 (sh)
SK (1)	SK17702002A3 (sh)
WO (1)	WO2001087890A1 (sh)
ZA (1)	ZA200209180B (sh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7262309B2 (en)	2002-04-10	2007-08-28	Glaxosmith Kline Istrazivocki Centar Zagreb, D.O.O.	1- or 3-thia-benzonaphthoazulenes as inhibitors of tumor necrosis factor production and intermediates for the preparation thereof

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HRP20020304B1 (en) *	2002-04-10	2008-04-30	GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o.	1-oxa-3-aza-dibenzoazulenes as inhibitors of tumor necrosis factor production and intermediates for the production thereof
HRP20020305A8 (en)	2002-04-10	2009-03-31	GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o.	2-thia-dibenzoazulenes as inhibitors of tumour necrosis factor production and intermediates for the preparation thereof
HRP20020441A2 (en) *	2002-05-21	2003-12-31	Pliva D D	1-oxa-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediate for preparation thereof
HRP20020440B1 (en) *	2002-05-21	2008-02-29	GlaxoSmithKline istra�iva�ki centar Zagreb d.o.o.	1-aza-dibenzoazulenes as inhibitors of tumor necrosis factor production and intermediates for the preparation thereof
HRP20020453A2 (en)	2002-05-23	2003-12-31	Pliva D D	1,3-diaza-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediate for preparation thereof
HRP20020452A2 (en)	2002-05-23	2004-02-29	Pliva D D	1,2-diaza-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediates for preparation thereof
HRP20020451A2 (en) *	2002-05-23	2003-12-31	Pliva D D	1-tia-3-aza-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediates for preparation thereof
HRP20030160A2 (en) *	2003-03-06	2005-04-30	Pliva-Istra�iva�ki institut d.o.o.	1-thiadibenzoazulene derivatives and biological action thereof
HRP20030324A2 (en)	2003-04-24	2005-02-28	Pliva-Istra�iva�ki institut d.o.o.	Compounds of antiinflammatory effect
EP1706394B1 (en) *	2003-11-12	2014-12-17	Dr. Reddy's Laboratories, Inc.	Preparation of escitalopram
HRP20030955A2 (en) *	2003-11-21	2005-08-31	Pliva-Istra�iva�ki institut d.o.o.	USE OF 1-OXADIBENZO[e,h]AZULENES FOR THE MANUFACTURE OF PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS
HRP20030954A2 (en) *	2003-11-21	2005-08-31	Pliva D.D.	USE OF 1-AZA-DIBENZO[e,h]AZULENES FOR THE MANUFACTURENT AND PREVENTION OF CENTRAL NERVOUS SYSTEM DISEASES AND DISORDERS
HRP20040104A2 (en) *	2004-01-30	2005-10-31	Pliva-Istra�iva�ki institut d.o.o.	Use of benzonaphthoazulenes for the manufacture of pharmaceutical formulations for the treatment and prevention of central nervous system diseases and disorders
ES2337915T3 (es)	2004-10-27	2010-04-30	Glaxosmithkline Istrazivacki Centar Zagreb D.O.O.	Conjugados con adtividad antiinflamatoria.
JP4912320B2 (ja) *	2004-12-07	2012-04-11	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	置換された四環式テトラヒドロピラン、ピロリジンおよびテトラヒドロチオフェン誘導体
JP2008532927A (ja) *	2005-01-13	2008-08-21	グラクソスミスクライン・イストラジヴァッキ・センタル・ザグレブ・ドルズバ・ゼー・オメイェノ・オドゴヴォルノスティオ	抗炎症マクロライド接合体
JP2009529057A (ja)	2006-03-08	2009-08-13	コートリア・コーポレーシヨン	Ｃｏｘ−関連胃損傷を予防するための非−選択的ｃｏｘ阻害剤との組み合わせ療法
WO2008094275A1 (en)	2007-01-30	2008-08-07	New York University	Peptides for treatment of conditions associated with nitric oxide
WO2008096755A1 (ja) *	2007-02-07	2008-08-14	Nippon Suisan Kaisha, Ltd.	バニロイド受容体（ｖｒ１）阻害剤及びその用途

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3711489A (en) *	1971-03-31	1973-01-16	Pfizer	Certain 8,9-dihydro(3,4,7,8)cycloocta(1,2-d)imidazoles
JPS53116385A (en) *	1977-03-19	1978-10-11	Hokuriku Pharmaceutical	Pyrazin derivative and method for its production
US4198421A (en) *	1978-11-30	1980-04-15	E. I. Du Pont De Nemours And Company	Antiinflammatory 2-substituted-dibenzo[2,3:6,7]oxepino[4,5-d]imidazoles
PL190960B1 (pl) *	1996-04-12	2006-02-28	Janssen Pharmaceutica Nv	Tetracykliczna pochodna tetrahydrofuranu, kompozycja farmaceutyczna i sposób wytwarzania tetracyklicznej pochodnej tetrahydrofuranu
GB9713368D0 (en) *	1997-06-25	1997-08-27	Weston Medical Ltd	Flame control
EP0887339A1 (de) *	1997-06-27	1998-12-30	Roche Diagnostics GmbH	Neue Azulenderivate und diese enthaltende Arzneimittel

2000
- 2000-05-17 HR HR20000310A patent/HRP20000310A2/hr not_active Application Discontinuation
2001
- 2001-05-16 BR BR0111202-3A patent/BR0111202A/pt not_active Application Discontinuation
- 2001-05-16 HU HU0302295A patent/HUP0302295A3/hu unknown
- 2001-05-16 EA EA200201223A patent/EA006069B1/ru not_active IP Right Cessation
- 2001-05-16 PT PT01929882T patent/PT1284977E/pt unknown
- 2001-05-16 DE DE60139070T patent/DE60139070D1/de not_active Expired - Lifetime
- 2001-05-16 WO PCT/HR2001/000027 patent/WO2001087890A1/en active IP Right Grant
- 2001-05-16 NZ NZ522553A patent/NZ522553A/en unknown
- 2001-05-16 GE GE5019A patent/GEP20043304B/en unknown
- 2001-05-16 SI SI200130930T patent/SI1284977T1/sl unknown
- 2001-05-16 CA CA2409090A patent/CA2409090C/en not_active Expired - Fee Related
- 2001-05-16 EP EP01929882A patent/EP1284977B1/en not_active Expired - Lifetime
- 2001-05-16 AT AT01929882T patent/ATE434619T1/de not_active IP Right Cessation
- 2001-05-16 PL PL365054A patent/PL204849B1/pl not_active IP Right Cessation
- 2001-05-16 AU AU2001256560A patent/AU2001256560B2/en not_active Ceased
- 2001-05-16 ES ES01929882T patent/ES2328335T3/es not_active Expired - Lifetime
- 2001-05-16 MX MXPA02011269A patent/MXPA02011269A/es active IP Right Grant
- 2001-05-16 DZ DZ013357A patent/DZ3357A1/fr active
- 2001-05-16 IL IL15280901A patent/IL152809A0/xx unknown
- 2001-05-16 EE EEP200200636A patent/EE200200636A/xx unknown
- 2001-05-16 JP JP2001584284A patent/JP2003533528A/ja active Pending
- 2001-05-16 CN CNB018115896A patent/CN1194976C/zh not_active Expired - Fee Related
- 2001-05-16 KR KR1020027015567A patent/KR100823064B1/ko not_active IP Right Cessation
- 2001-05-16 AU AU5656001A patent/AU5656001A/xx active Pending
- 2001-05-16 DK DK01929882T patent/DK1284977T3/da active
- 2001-05-16 CZ CZ20024090A patent/CZ301770B6/cs not_active IP Right Cessation
- 2001-05-16 RS YUP-841/02A patent/RS50893B/sr unknown
- 2001-05-16 SK SK1770-2002A patent/SK17702002A3/sk unknown
- 2001-05-17 AR ARP010102339A patent/AR030562A1/es active IP Right Grant
2002
- 2002-11-11 MA MA26901A patent/MA27125A1/fr unknown
- 2002-11-12 ZA ZA200209180A patent/ZA200209180B/en unknown
- 2002-11-14 IS IS6621A patent/IS6621A/is unknown
- 2002-11-15 NO NO20025510A patent/NO20025510L/no not_active Application Discontinuation
- 2002-11-18 US US10/298,217 patent/US6897211B2/en not_active Expired - Fee Related
- 2002-12-17 CR CR6860A patent/CR6860A/es not_active Application Discontinuation
- 2002-12-17 BG BG107399A patent/BG65967B1/bg unknown
2003
- 2003-12-11 HK HK03109004A patent/HK1056719A1/xx not_active IP Right Cessation
2005
- 2005-03-25 US US11/090,743 patent/US20050171091A1/en not_active Abandoned
2009
- 2009-08-20 CY CY20091100888T patent/CY1109328T1/el unknown

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7262309B2 (en)	2002-04-10	2007-08-28	Glaxosmith Kline Istrazivocki Centar Zagreb, D.O.O.	1- or 3-thia-benzonaphthoazulenes as inhibitors of tumor necrosis factor production and intermediates for the preparation thereof

Also Published As

Publication number	Publication date
AU5656001A (en)	2001-11-26
BG65967B1 (bg)	2010-07-30
US20050171091A1 (en)	2005-08-04
PT1284977E (pt)	2009-09-09
IS6621A (is)	2002-11-14
MXPA02011269A (es)	2003-06-06
EE200200636A (et)	2004-04-15
BR0111202A (pt)	2003-04-01
EP1284977A1 (en)	2003-02-26
AU2001256560B2 (en)	2005-10-06
JP2003533528A (ja)	2003-11-11
RS50893B (sr)	2010-08-31
GEP20043304B (en)	2004-02-10
CZ301770B6 (cs)	2010-06-16
SI1284977T1 (sl)	2009-10-31
EA200201223A1 (ru)	2003-06-26
HUP0302295A2 (hu)	2003-10-28
DZ3357A1 (fr)	2001-11-22
DK1284977T3 (da)	2009-09-14
ATE434619T1 (de)	2009-07-15
CZ20024090A3 (cs)	2003-05-14
NO20025510D0 (no)	2002-11-15
KR20030010625A (ko)	2003-02-05
NZ522553A (en)	2005-04-29
ES2328335T3 (es)	2009-11-12
CA2409090C (en)	2010-06-29
CY1109328T1 (el)	2012-05-23
US6897211B2 (en)	2005-05-24
CA2409090A1 (en)	2001-11-22
PL365054A1 (en)	2004-12-27
ZA200209180B (en)	2003-11-12
HUP0302295A3 (en)	2007-03-28
YU84102A (sh)	2006-01-16
BG107399A (bg)	2003-09-30
CR6860A (es)	2008-06-02
WO2001087890A1 (en)	2001-11-22
MA27125A1 (fr)	2005-01-03
US20030153750A1 (en)	2003-08-14
SK17702002A3 (sk)	2003-10-07
DE60139070D1 (de)	2009-08-06
IL152809A0 (en)	2003-06-24
AR030562A1 (es)	2003-08-27
NO20025510L (no)	2003-01-14
KR100823064B1 (ko)	2008-04-18
EA006069B1 (ru)	2005-08-25
PL204849B1 (pl)	2010-02-26
EP1284977B1 (en)	2009-06-24
HK1056719A1 (en)	2004-02-27
CN1194976C (zh)	2005-03-30
CN1437605A (zh)	2003-08-20

Publication	Publication Date	Title
HRP20000310A2 (en)	2002-02-28	New dibenzoazulene compounds as tumor necrosis factor inhibitors
AU2001256560A1 (en)	2002-02-14	Thienodibenzoazulene compounds as tumor necrosis factor inhibitors
ES2290492T3 (es)	2008-02-16	1-aza-dibenzoazulenos como inhibidores de la produccion del factor de necrosis tumoral e intermedios para su peparacion.
DE60302344T2 (de)	2006-07-27	1- oder 3-thia-benzonaphthoazulene als inhibitoren der produktion von tumornekrosefaktor und zwischenprodukte für deren herstellung
CN100354277C (zh)	2007-12-12	作为肿瘤坏死因子产生抑制剂的1,3－二氮杂－二苯并薁类和制备该抑制剂的中间体
DE60304048T2 (de)	2006-10-19	2-thia-dibenzoazulene als inhibitoren der produktion von tumornekrosefaktor und zwischenprodukte für deren herstellung
HRP20020441A2 (en)	2003-12-31	1-oxa-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediate for preparation thereof
DE60304047T2 (de)	2006-11-09	1-oxa-3-aza-dibenzoazulene als inhibitoren der produktion von tumornekrosefaktor und zwischenprodukte für deren herstellung
HRP20020451A2 (en)	2003-12-31	1-tia-3-aza-dibenzoazulen as inhibitor of production of tumor necrosis factors and intermediates for preparation thereof
HRP20030160A2 (en)	2005-04-30	1-thiadibenzoazulene derivatives and biological action thereof
KR20050016336A (ko)	2005-02-21	종양괴사인자 생성 억제제로서의 2-티아-디벤조아줄렌 및그의 제조를 위한 중간체

Legal Events

Date	Code	Title	Description
2002-02-28	A1OB	Publication of a patent application
2002-07-18	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2007-01-08	PNAN	Change of the applicant name, address/residence	Owner name: GLAXOSMITHKLINE ISTRAZIVACKI CENTAR ZAGREB D.O.O.,
2007-01-08	PPPP	Transfer of rights	Owner name: PLIVA-ISTRAZIVACKI INSTITUT D.O.O., HR
2010-05-12	ODRP	Renewal fee for the maintenance of a patent	Payment date: 20100512 Year of fee payment: 11
2011-11-28	ODBI	Application refused

HRP20000310A2 - New dibenzoazulene compounds as tumor necrosis factor inhibitors - Google Patents

Info

Links

Classifications

Landscapes

Priority Applications (39)

Applications Claiming Priority (1)

Publications (1)

Family

ID=10947110

Family Applications (1)

Country Status (37)

Cited By (1)

Families Citing this family (19)

Family Cites Families (6)

Cited By (1)

Also Published As

Similar Documents

Legal Events