NZ508790A - Heterocyclic compounds and methods to treat cardiac failure and other disorders - Google Patents
Heterocyclic compounds and methods to treat cardiac failure and other disordersInfo
- Publication number
- NZ508790A NZ508790A NZ508790A NZ50879099A NZ508790A NZ 508790 A NZ508790 A NZ 508790A NZ 508790 A NZ508790 A NZ 508790A NZ 50879099 A NZ50879099 A NZ 50879099A NZ 508790 A NZ508790 A NZ 508790A
- Authority
- NZ
- New Zealand
- Prior art keywords
- carboxamide
- indole
- benzimidazole
- benzylpiperidinyl
- alkyl
- Prior art date
Links
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 14
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 230000004044 response Effects 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- -1 acetyl 4-benzylpiperidinyl indole-5-carboxamide Chemical compound 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 125000001424 substituent group Chemical group 0.000 claims description 58
- 235000011468 Albizia julibrissin Nutrition 0.000 claims description 56
- 241001070944 Mimosa Species 0.000 claims description 56
- 238000002360 preparation method Methods 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- XQIKXPXSWYNRSF-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-1h-indole-5-carboxamide Chemical compound C=1C2=CC(C(=O)N)=CC=C2NC=1N(CC1)CCC1CC1=CC=CC=C1 XQIKXPXSWYNRSF-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- UHYKYBSPFDZEGC-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-6-methoxy-1h-indole-5-carboxamide Chemical compound C=1C=2C=C(C(N)=O)C(OC)=CC=2NC=1N(CC1)CCC1CC1=CC=CC=C1 UHYKYBSPFDZEGC-UHFFFAOYSA-N 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000009525 Myocarditis Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- RMDKPGHJTYGMND-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-3-(2,2,2-trifluoroacetyl)-1h-indole-5-carboxamide Chemical compound FC(F)(F)C(=O)C=1C2=CC(C(=O)N)=CC=C2NC=1N(CC1)CCC1CC1=CC=CC=C1 RMDKPGHJTYGMND-UHFFFAOYSA-N 0.000 claims description 2
- DBCREKNQLGREHQ-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-[2-hydroxy-3-(propylamino)propyl]-1h-indole-5-carboxamide Chemical compound C=1C2=CC(C(=O)NCC(O)CNCCC)=CC=C2NC=1N(CC1)CCC1CC1=CC=CC=C1 DBCREKNQLGREHQ-UHFFFAOYSA-N 0.000 claims description 2
- SMXYQSMGYLNSBS-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-propanoyl-1h-indole-5-carboxamide Chemical compound C=1C2=CC(C(=O)NC(=O)CC)=CC=C2NC=1N(CC1)CCC1CC1=CC=CC=C1 SMXYQSMGYLNSBS-UHFFFAOYSA-N 0.000 claims description 2
- JMCDIWOHYOOZDN-UHFFFAOYSA-N 2-[4-[(2,3-difluorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=CC(F)=C1F JMCDIWOHYOOZDN-UHFFFAOYSA-N 0.000 claims description 2
- DTPRXTJBIXTMEF-UHFFFAOYSA-N 2-[4-[(2-chlorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=CC=C1Cl DTPRXTJBIXTMEF-UHFFFAOYSA-N 0.000 claims description 2
- NXZFBPDLXITXDM-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 NXZFBPDLXITXDM-UHFFFAOYSA-N 0.000 claims description 2
- OTRLVAHNGOIIIM-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-methoxy-1h-indole-5-carboxamide Chemical compound C=1C=2C(OC)=C(C(N)=O)C=CC=2NC=1N(CC1)CCC1CC1=CC=C(F)C=C1 OTRLVAHNGOIIIM-UHFFFAOYSA-N 0.000 claims description 2
- INJUDDVHJZUWTQ-UHFFFAOYSA-N 2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-6-methoxy-1h-indole-5-carboxamide Chemical compound C=1C=2C=C(C(N)=O)C(OC)=CC=2NC=1N(CC1)CCC1CC1=CC=C(F)C=C1 INJUDDVHJZUWTQ-UHFFFAOYSA-N 0.000 claims description 2
- LOJJLAGBTAGITQ-UHFFFAOYSA-N 2-[4-[(4-methylsulfanylphenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound C1=CC(SC)=CC=C1CN1CCN(C=2NC3=CC(=CC=C3N=2)C(N)=O)CC1 LOJJLAGBTAGITQ-UHFFFAOYSA-N 0.000 claims description 2
- VVDLGDFMJJGBIW-UHFFFAOYSA-N 2-[4-benzyl-3-(2,2,2-trifluoroacetyl)piperidin-1-yl]-1h-indole-5-carboxamide Chemical compound C=1C2=CC(C(=O)N)=CC=C2NC=1N(CC1C(=O)C(F)(F)F)CCC1CC1=CC=CC=C1 VVDLGDFMJJGBIW-UHFFFAOYSA-N 0.000 claims description 2
- PBONXFAGZYYDTE-UHFFFAOYSA-N 4-chloro-2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-1h-indole-5-carboxamide Chemical compound C=1C2=C(Cl)C(C(=O)N)=CC=C2NC=1N(CC1)CCC1CC1=CC=C(F)C=C1 PBONXFAGZYYDTE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 2
- 208000033626 Renal failure acute Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 201000011040 acute kidney failure Diseases 0.000 claims description 2
- 208000012998 acute renal failure Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- KJLFFCRGGGXQKE-UHFFFAOYSA-N 1h-indole-6-carboxamide Chemical compound NC(=O)C1=CC=C2C=CNC2=C1 KJLFFCRGGGXQKE-UHFFFAOYSA-N 0.000 claims 1
- MZUBLCVAGGWWCH-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=CC=C1 MZUBLCVAGGWWCH-UHFFFAOYSA-N 0.000 claims 1
- SCBGJAMOFAPVJB-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-4-methoxy-1h-indole-5-carboxamide Chemical compound C=1C=2C(OC)=C(C(N)=O)C=CC=2NC=1N(CC1)CCC1CC1=CC=CC=C1 SCBGJAMOFAPVJB-UHFFFAOYSA-N 0.000 claims 1
- XASBBUBUFRHSCO-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-(pyridin-4-ylmethyl)-1h-indole-5-carboxamide Chemical compound C=1C=C2NC(N3CCC(CC=4C=CC=CC=4)CC3)=CC2=CC=1C(=O)NCC1=CC=NC=C1 XASBBUBUFRHSCO-UHFFFAOYSA-N 0.000 claims 1
- NEOZRCLVNSDKMU-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-(pyridine-4-carbonyl)-1h-indole-5-carboxamide Chemical compound C=1C=NC=CC=1C(=O)NC(=O)C(C=C1C=2)=CC=C1NC=2N(CC1)CCC1CC1=CC=CC=C1 NEOZRCLVNSDKMU-UHFFFAOYSA-N 0.000 claims 1
- UHGDXXRCTDEHQD-UHFFFAOYSA-N 2-(4-benzylpiperidin-1-yl)-n-[3-(cyclohexylmethylamino)-2-hydroxypropyl]-1h-indole-5-carboxamide Chemical compound C=1C=C2NC(N3CCC(CC=4C=CC=CC=4)CC3)=CC2=CC=1C(=O)NCC(O)CNCC1CCCCC1 UHGDXXRCTDEHQD-UHFFFAOYSA-N 0.000 claims 1
- JPURORVGEFTMTK-UHFFFAOYSA-N 2-[4-(2,4-dichlorobenzoyl)piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1Cl JPURORVGEFTMTK-UHFFFAOYSA-N 0.000 claims 1
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- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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Landscapes
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Applications Claiming Priority (4)
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|---|---|---|---|
| US8653198P | 1998-05-22 | 1998-05-22 | |
| US09/128,137 US6130235A (en) | 1998-05-22 | 1998-08-03 | Compounds and methods to treat cardiac failure and other disorders |
| US09/275,176 US6340685B1 (en) | 1998-05-22 | 1999-03-24 | Compounds and methods to treat cardiac failure and other disorders |
| PCT/US1999/011222 WO1999061426A1 (en) | 1998-05-22 | 1999-05-21 | Heterocyclic compounds and methods to treat cardiac failure and other disorders |
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| NZ508790A true NZ508790A (en) | 2003-10-31 |
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| NZ508790A NZ508790A (en) | 1998-05-22 | 1999-05-21 | Heterocyclic compounds and methods to treat cardiac failure and other disorders |
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| NZ (1) | NZ508790A (https=) |
| PL (1) | PL346345A1 (https=) |
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| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| US6979686B1 (en) | 2001-12-07 | 2005-12-27 | Pharmacia Corporation | Substituted pyrazoles as p38 kinase inhibitors |
| AU7726898A (en) | 1997-05-22 | 1998-12-11 | G.D. Searle & Co. | Pyrazole derivatives as p38 kinase inhibitors |
| US6589954B1 (en) | 1998-05-22 | 2003-07-08 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6867209B1 (en) | 1998-05-22 | 2005-03-15 | Scios, Inc. | Indole-type derivatives as inhibitors of p38 kinase |
| US6448257B1 (en) | 1998-05-22 | 2002-09-10 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
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| WO1998028292A1 (en) * | 1996-12-23 | 1998-07-02 | Smithkline Beecham Corporation | Novel piperidine containing compounds |
| GB9804734D0 (en) * | 1998-03-05 | 1998-04-29 | Pfizer Ltd | Compounds |
-
1999
- 1999-05-21 AT AT99924412T patent/ATE316961T1/de not_active IP Right Cessation
- 1999-05-21 EP EP99924412A patent/EP1080078B1/en not_active Expired - Lifetime
- 1999-05-21 JP JP2000550832A patent/JP2002516314A/ja active Pending
- 1999-05-21 HU HU0203657A patent/HUP0203657A3/hu unknown
- 1999-05-21 BR BR9911069-5A patent/BR9911069A/pt not_active Application Discontinuation
- 1999-05-21 WO PCT/US1999/011222 patent/WO1999061426A1/en not_active Ceased
- 1999-05-21 CN CNB998071528A patent/CN1229351C/zh not_active Expired - Fee Related
- 1999-05-21 NZ NZ508790A patent/NZ508790A/en unknown
- 1999-05-21 AU AU40920/99A patent/AU769465B2/en not_active Ceased
- 1999-05-21 KR KR1020007013126A patent/KR100605140B1/ko not_active Expired - Fee Related
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- 1999-05-21 CA CA002332459A patent/CA2332459A1/en not_active Abandoned
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2000
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Also Published As
| Publication number | Publication date |
|---|---|
| DE69929689T2 (de) | 2006-11-02 |
| JP2002516314A (ja) | 2002-06-04 |
| NO20005881L (no) | 2001-01-09 |
| WO1999061426A1 (en) | 1999-12-02 |
| EP1080078A1 (en) | 2001-03-07 |
| ATE316961T1 (de) | 2006-02-15 |
| CN1305464A (zh) | 2001-07-25 |
| DE69929689D1 (de) | 2006-04-13 |
| HUP0203657A3 (en) | 2005-03-29 |
| AU2004201809A1 (en) | 2004-05-27 |
| CN1229351C (zh) | 2005-11-30 |
| PL346345A1 (en) | 2002-02-11 |
| KR100605140B1 (ko) | 2006-07-28 |
| KR20010070946A (ko) | 2001-07-28 |
| ES2258331T3 (es) | 2006-08-16 |
| AU769465B2 (en) | 2004-01-29 |
| BR9911069A (pt) | 2001-02-06 |
| AU4092099A (en) | 1999-12-13 |
| NO20005881D0 (no) | 2000-11-21 |
| HUP0203657A2 (hu) | 2003-03-28 |
| EP1080078B1 (en) | 2006-02-01 |
| HK1034707A1 (en) | 2001-11-02 |
| NO320299B1 (no) | 2005-11-21 |
| CA2332459A1 (en) | 1999-12-02 |
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