JP2006516610A - チエノ［２，３−ｃ］ピリジン誘導体を含む薬剤組成物、及びその使用 - Google Patents
チエノ［２，３−ｃ］ピリジン誘導体を含む薬剤組成物、及びその使用 Download PDFInfo
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- JP2006516610A JP2006516610A JP2006502633A JP2006502633A JP2006516610A JP 2006516610 A JP2006516610 A JP 2006516610A JP 2006502633 A JP2006502633 A JP 2006502633A JP 2006502633 A JP2006502633 A JP 2006502633A JP 2006516610 A JP2006516610 A JP 2006516610A
- Authority
- JP
- Japan
- Prior art keywords
- pyridine
- amino
- benzoyl
- sulfonyl
- tetrahydrothieno
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 68
- GDQBPBMIAFIRIU-UHFFFAOYSA-N thieno[2,3-c]pyridine Chemical class C1=NC=C2SC=CC2=C1 GDQBPBMIAFIRIU-UHFFFAOYSA-N 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 228
- 229920002683 Glycosaminoglycan Polymers 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 70
- 230000003993 interaction Effects 0.000 claims abstract description 46
- 201000010099 disease Diseases 0.000 claims abstract description 40
- 230000001404 mediated effect Effects 0.000 claims abstract description 40
- 238000011282 treatment Methods 0.000 claims abstract description 33
- 208000035475 disorder Diseases 0.000 claims abstract description 30
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 25
- 201000011510 cancer Diseases 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 206010002022 amyloidosis Diseases 0.000 claims abstract description 7
- 230000003612 virological effect Effects 0.000 claims abstract description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
- -1 2-[[4-[[Ethyl (phenylmethyl) amino] sulfonyl] benzoyl] amino] -6-ethyl-4,5,6,7-tetrahydrothieno [2,3-c] pyridine-3-carboxamide Thieno [2,3-c] pyridine compound Chemical class 0.000 claims description 128
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 110
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 109
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 103
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 72
- 229920000669 heparin Polymers 0.000 claims description 70
- 229960002897 heparin Drugs 0.000 claims description 67
- 108010092694 L-Selectin Proteins 0.000 claims description 58
- 239000000203 mixture Substances 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 40
- 210000004027 cell Anatomy 0.000 claims description 37
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 35
- 239000004480 active ingredient Substances 0.000 claims description 31
- 210000000265 leukocyte Anatomy 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 230000000694 effects Effects 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
- 108010035766 P-Selectin Proteins 0.000 claims description 25
- 102100023472 P-selectin Human genes 0.000 claims description 25
- 210000000440 neutrophil Anatomy 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 claims description 21
- 229920002971 Heparan sulfate Polymers 0.000 claims description 20
- 235000005152 nicotinamide Nutrition 0.000 claims description 20
- 239000011570 nicotinamide Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 18
- 230000021164 cell adhesion Effects 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 230000004054 inflammatory process Effects 0.000 claims description 17
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 201000006417 multiple sclerosis Diseases 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 12
- 125000001589 carboacyl group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 230000012292 cell migration Effects 0.000 claims description 12
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 12
- 230000008595 infiltration Effects 0.000 claims description 12
- 238000001764 infiltration Methods 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 206010027476 Metastases Diseases 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 230000006378 damage Effects 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 11
- 125000004494 ethyl ester group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 239000005973 Carvone Substances 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 230000009401 metastasis Effects 0.000 claims description 10
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims description 10
- XTNPTCYECQYVTN-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(diethylsulfamoyl)benzamide Chemical compound C1=CC(S(=O)(=O)N(CC)CC)=CC=C1C(=O)NC1=C(C=2SC3=CC=CC=C3N=2)C(CCN(C)C2)=C2S1 XTNPTCYECQYVTN-UHFFFAOYSA-N 0.000 claims description 10
- CVAIQWZNGNUDNR-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-[methyl(phenyl)sulfamoyl]benzamide Chemical compound C=1C=C(C(=O)NC2=C(C=3CCN(C)CC=3S2)C=2SC3=CC=CC=C3N=2)C=CC=1S(=O)(=O)N(C)C1=CC=CC=C1 CVAIQWZNGNUDNR-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- VPEMNPODXCXJJF-UHFFFAOYSA-N 2-[[4-[benzyl(ethyl)sulfamoyl]benzoyl]amino]-6-ethyl-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxamide Chemical compound C=1C=C(C(=O)NC2=C(C=3CCN(CC)CC=3S2)C(N)=O)C=CC=1S(=O)(=O)N(CC)CC1=CC=CC=C1 VPEMNPODXCXJJF-UHFFFAOYSA-N 0.000 claims description 9
- YRSSRCFBMMLSLW-UHFFFAOYSA-N 6-ethyl-2-[[4-(4-methylpiperazin-1-yl)sulfonylbenzoyl]amino]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxamide Chemical compound C1N(CC)CCC(C=2C(N)=O)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N1CCN(C)CC1 YRSSRCFBMMLSLW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 238000000338 in vitro Methods 0.000 claims description 9
- 206010053567 Coagulopathies Diseases 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
- GQIDNMVCAHJPCE-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-ethyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(diethylsulfamoyl)benzamide Chemical compound C1=CC(S(=O)(=O)N(CC)CC)=CC=C1C(=O)NC1=C(C=2SC3=CC=CC=C3N=2)C(CCN(CC)C2)=C2S1 GQIDNMVCAHJPCE-UHFFFAOYSA-N 0.000 claims description 8
- BQHHKCLXPYGPGT-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-ethyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-[butyl(ethyl)sulfamoyl]benzamide Chemical compound C1=CC(S(=O)(=O)N(CC)CCCC)=CC=C1C(=O)NC1=C(C=2SC3=CC=CC=C3N=2)C(CCN(CC)C2)=C2S1 BQHHKCLXPYGPGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 208000032839 leukemia Diseases 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 6
- 125000005002 aryl methyl group Chemical group 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 5
- ZOMTULULPOPWSY-UHFFFAOYSA-N 6-ethyl-n-methyl-2-[[4-(4-methylpiperazin-1-yl)sulfonylbenzoyl]amino]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxamide Chemical compound C1N(CC)CCC(C=2C(=O)NC)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N1CCN(C)CC1 ZOMTULULPOPWSY-UHFFFAOYSA-N 0.000 claims description 5
- PYMLRHLGNABFST-UHFFFAOYSA-N 6-ethyl-n-methyl-2-[[4-[methyl(phenyl)sulfamoyl]benzoyl]amino]-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxamide Chemical compound C1N(CC)CCC(C=2C(=O)NC)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N(C)C1=CC=CC=C1 PYMLRHLGNABFST-UHFFFAOYSA-N 0.000 claims description 5
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 5
- 229920000045 Dermatan sulfate Polymers 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000003857 carboxamides Chemical class 0.000 claims description 5
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 5
- USKFCOOWLKKDLE-UHFFFAOYSA-N ethyl 2-[[4-(4-ethoxycarbonylpiperazin-1-yl)sulfonylbenzoyl]amino]-6-propan-2-yl-5,7-dihydro-4h-thieno[2,3-c]pyridine-3-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1S(=O)(=O)C1=CC=C(C(=O)NC2=C(C=3CCN(CC=3S2)C(C)C)C(=O)OCC)C=C1 USKFCOOWLKKDLE-UHFFFAOYSA-N 0.000 claims description 5
- FLQYXSJREWKIED-UHFFFAOYSA-N ethyl 4-[4-[(3-carbamoyl-5,5,7,7-tetramethyl-4,6-dihydrothieno[2,3-c]pyridin-2-yl)carbamoyl]phenyl]sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1S(=O)(=O)C1=CC=C(C(=O)NC2=C(C3=C(C(NC(C)(C)C3)(C)C)S2)C(N)=O)C=C1 FLQYXSJREWKIED-UHFFFAOYSA-N 0.000 claims description 5
- KMJHAJQYFYDERS-UHFFFAOYSA-N ethyl 4-[4-[[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]carbamoyl]phenyl]sulfonylpiperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1S(=O)(=O)C1=CC=C(C(=O)NC2=C(C=3CCN(C)CC=3S2)C=2SC3=CC=CC=C3N=2)C=C1 KMJHAJQYFYDERS-UHFFFAOYSA-N 0.000 claims description 5
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- QSSISUHOHCEHRQ-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-benzyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(diethylsulfamoyl)benzamide Chemical compound C1=CC(S(=O)(=O)N(CC)CC)=CC=C1C(=O)NC1=C(C=2SC3=CC=CC=C3N=2)C(CCN(CC=2C=CC=CC=2)C2)=C2S1 QSSISUHOHCEHRQ-UHFFFAOYSA-N 0.000 claims description 5
- CBSHUWKSSHJYPZ-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-ethyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(4-methylpiperazin-1-yl)sulfonylbenzamide Chemical compound C1N(CC)CCC(C=2C=3SC4=CC=CC=C4N=3)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N1CCN(C)CC1 CBSHUWKSSHJYPZ-UHFFFAOYSA-N 0.000 claims description 5
- YMDJVTMDUDKYKZ-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(4-methylpiperazin-1-yl)sulfonylbenzamide Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C(=O)NC2=C(C=3CCN(C)CC=3S2)C=2SC3=CC=CC=C3N=2)C=C1 YMDJVTMDUDKYKZ-UHFFFAOYSA-N 0.000 claims description 5
- VXXJBJRWVMMHRU-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-[(3,3,5-trimethyl-7-azabicyclo[3.2.1]octan-7-yl)sulfonyl]benzamide Chemical compound C1=CC=C2SC(C3=C(NC(=O)C=4C=CC(=CC=4)S(=O)(=O)N4C5CC(CC(C)(C)C5)(C)C4)SC4=C3CCN(C4)C)=NC2=C1 VXXJBJRWVMMHRU-UHFFFAOYSA-N 0.000 claims description 5
- FLSOXNKHAMQZIN-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-methyl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-morpholin-4-ylsulfonylbenzamide Chemical compound C1N(C)CCC(C=2C=3SC4=CC=CC=C4N=3)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N1CCOCC1 FLSOXNKHAMQZIN-UHFFFAOYSA-N 0.000 claims description 5
- UQKSAQVUELOLQL-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-propan-2-yl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-morpholin-4-ylsulfonylbenzamide Chemical compound C1N(C(C)C)CCC(C=2C=3SC4=CC=CC=C4N=3)=C1SC=2NC(=O)C(C=C1)=CC=C1S(=O)(=O)N1CCOCC1 UQKSAQVUELOLQL-UHFFFAOYSA-N 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 claims description 4
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical group CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 claims description 4
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- VIYWMMCQNUKAEQ-UHFFFAOYSA-N n-[3-(1,3-benzothiazol-2-yl)-6-propan-2-yl-5,7-dihydro-4h-thieno[2,3-c]pyridin-2-yl]-4-(diethylsulfamoyl)benzamide Chemical compound C1=CC(S(=O)(=O)N(CC)CC)=CC=C1C(=O)NC1=C(C=2SC3=CC=CC=C3N=2)C(CCN(C2)C(C)C)=C2S1 VIYWMMCQNUKAEQ-UHFFFAOYSA-N 0.000 claims description 3
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| IL15430603A IL154306A0 (en) | 2003-02-05 | 2003-02-05 | Pharmaceutical compositions comprising thieno [2,3-c] pyridine derivatives and use thereof |
| PCT/IL2004/000121 WO2004069149A2 (en) | 2003-02-05 | 2004-02-05 | Pharmaceutical compositions comprising thieno[2,3-c]pyridine derivatives and use thereof |
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| EP (1) | EP1589970A4 (enExample) |
| JP (1) | JP2006516610A (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014533733A (ja) * | 2011-11-29 | 2014-12-15 | ギリアド ファーマセット エルエルシー | Ｃ型肝炎ウイルスを処置するための組成物および方法 |
| JP2020514308A (ja) * | 2017-01-13 | 2020-05-21 | 東菱薬品工業株式会社 | 好中球活性化調節剤 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060275214A1 (en) * | 2003-12-30 | 2006-12-07 | Rimonyx Pharmaceuticals Ltd. | Methods of screening for anti-inflammatory drugs and use thereof |
| WO2005089068A2 (en) * | 2004-03-24 | 2005-09-29 | Rimonyx Pharmaceuticals Ltd. | Pharmaceutical compositions comprising anti-inflammatory quinazolinecarboxamide derivatives |
| EP1753512B1 (en) | 2004-05-28 | 2008-07-09 | Nycomed GmbH | Tetrahydropyridothiophenes |
| DE602005007220D1 (de) | 2004-06-04 | 2008-07-10 | Nycomed Gmbh | Tetrahydropyridothiophenen zur verwendung in der behandlung von krebs |
| JP2008501768A (ja) * | 2004-06-11 | 2008-01-24 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規の化合物及びテトラヒドロピリドチオフェンの使用 |
| US8338648B2 (en) * | 2004-06-12 | 2012-12-25 | Signum Biosciences, Inc. | Topical compositions and methods for epithelial-related conditions |
| CA2596202A1 (en) | 2005-02-09 | 2006-08-17 | Altana Pharma Ag | Tetrahydropyridothiophenes for the treatment of proliferative diseases such as cancer |
| JP2008530053A (ja) | 2005-02-11 | 2008-08-07 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌の治療のための抗増殖性剤としてのテトラヒドロピリドチオフェン |
| AU2006251167A1 (en) | 2005-05-25 | 2006-11-30 | 4Sc Ag | Tetrahydropyridothiophenes for use in the treatment of cancer |
| AU2006251169A1 (en) | 2005-05-25 | 2006-11-30 | 4Sc Ag | Tetrahydropyridothiophenes for use in the treatment of cancer |
| US20100298370A1 (en) * | 2006-03-20 | 2010-11-25 | Paul Gregor | Benzothiazolyl thienopyridine derivatives and uses thereof |
| US8466149B2 (en) | 2007-08-15 | 2013-06-18 | Merck Sharp & Dohme Corp. | 6-substituted sulfonyl azabicyclo[3.2.1]octanes useful to inhibit 11β-hydroxysteroid dehydrogenase type-I |
| RU2364597C1 (ru) * | 2007-12-14 | 2009-08-20 | Андрей Александрович Иващенко | ГЕТЕРОЦИКЛИЧЕСКИЕ ИНГИБИТОРЫ Hh-СИГНАЛЬНОГО КАСКАДА, ЛЕКАРСТВЕННЫЕ КОМПОЗИЦИИ НА ИХ ОСНОВЕ И СПОСОБ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С АББЕРАНТНОЙ АКТИВНОСТЬЮ Hh СИГНАЛЬНОЙ СИСТЕМЫ |
| EP2307440A4 (en) * | 2008-07-01 | 2012-12-19 | Zacharon Pharmaceuticals Inc | HEPARAN SULFATE INHIBITORS |
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| WO2021050994A1 (en) * | 2019-09-13 | 2021-03-18 | Aerie Pharmaceuticals, Inc. | Heterobicyclic carboxamides and uses thereof |
| AU2022341967A1 (en) * | 2021-09-07 | 2024-05-16 | Gismo Therapeutics, Inc. | Compounds and pharmaceutical compositions comprising inhibitors of amyloid peptide interactions with glycosaminoglycans, methods of treatment, and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000075145A1 (en) * | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| JP2001151780A (ja) * | 1999-11-30 | 2001-06-05 | Nikken Chem Co Ltd | ４，５，６，７−テトラヒドロチエノ〔２，３−ｃ〕ピリジン化合物 |
| JP2002517396A (ja) * | 1998-06-04 | 2002-06-18 | アボット・ラボラトリーズ | 細胞接着阻害抗炎症性化合物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
-
2003
- 2003-02-05 IL IL15430603A patent/IL154306A0/xx unknown
-
2004
- 2004-02-05 KR KR1020057014345A patent/KR20050100655A/ko not_active Withdrawn
- 2004-02-05 CN CNA2004800093693A patent/CN1771037A/zh active Pending
- 2004-02-05 MX MXPA05008397A patent/MXPA05008397A/es not_active Application Discontinuation
- 2004-02-05 WO PCT/IL2004/000121 patent/WO2004069149A2/en not_active Ceased
- 2004-02-05 US US10/543,065 patent/US7365080B2/en not_active Expired - Fee Related
- 2004-02-05 JP JP2006502633A patent/JP2006516610A/ja not_active Ceased
- 2004-02-05 CA CA002515102A patent/CA2515102A1/en not_active Abandoned
- 2004-02-05 EP EP04708427A patent/EP1589970A4/en not_active Withdrawn
- 2004-02-05 AU AU2004210241A patent/AU2004210241A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002517396A (ja) * | 1998-06-04 | 2002-06-18 | アボット・ラボラトリーズ | 細胞接着阻害抗炎症性化合物 |
| WO2000075145A1 (en) * | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| JP2001151780A (ja) * | 1999-11-30 | 2001-06-05 | Nikken Chem Co Ltd | ４，５，６，７−テトラヒドロチエノ〔２，３−ｃ〕ピリジン化合物 |
Non-Patent Citations (1)
| Title |
|---|
| JPN6010027305, ＢＡＬＡＫＩＮ，Ｋ．Ｖ． ｅｔ ａｌ, "Ｐｒｏｐｅｒｔｙ−ｂａｓｅｄ ｄｅｓｉｇｎ ｏｆ ＧＰＣＲ−ｔａｒｇｅｔｅｄ ｌｉｂｒａｒｙ", Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍｉｃａｌ Ｉｎｆｏｒｍａｔｉｏｎ ａｎｄ Ｃｏｍｐｕｔｅｒ Ｓｃｉｅｎｃｅｓ, 2002, Ｖｏｌ．４２， Ｎｏ．６, ｐｐ．１３３２−１３４２ * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014533733A (ja) * | 2011-11-29 | 2014-12-15 | ギリアド ファーマセット エルエルシー | Ｃ型肝炎ウイルスを処置するための組成物および方法 |
| JP2016053096A (ja) * | 2011-11-29 | 2016-04-14 | ギリアド ファーマセット エルエルシー | Ｃ型肝炎ウイルスを処置するための組成物および方法 |
| JP2020514308A (ja) * | 2017-01-13 | 2020-05-21 | 東菱薬品工業株式会社 | 好中球活性化調節剤 |
| JP7100854B2 (ja) | 2017-01-13 | 2022-07-14 | 東菱薬品工業株式会社 | 好中球活性化調節剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1589970A2 (en) | 2005-11-02 |
| KR20050100655A (ko) | 2005-10-19 |
| US7365080B2 (en) | 2008-04-29 |
| MXPA05008397A (es) | 2006-02-17 |
| US20060135529A1 (en) | 2006-06-22 |
| EP1589970A4 (en) | 2008-05-21 |
| CN1771037A (zh) | 2006-05-10 |
| WO2004069149A2 (en) | 2004-08-19 |
| AU2004210241A1 (en) | 2004-08-19 |
| WO2004069149A3 (en) | 2004-11-25 |
| IL154306A0 (en) | 2003-09-17 |
| CA2515102A1 (en) | 2004-08-19 |
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