ES2258331T3 - Compuestos heterociclicos y procedimientos de tratamiento de insuficiencia cardiaca y otros trastornos. - Google Patents
Compuestos heterociclicos y procedimientos de tratamiento de insuficiencia cardiaca y otros trastornos.Info
- Publication number
- ES2258331T3 ES2258331T3 ES99924412T ES99924412T ES2258331T3 ES 2258331 T3 ES2258331 T3 ES 2258331T3 ES 99924412 T ES99924412 T ES 99924412T ES 99924412 T ES99924412 T ES 99924412T ES 2258331 T3 ES2258331 T3 ES 2258331T3
- Authority
- ES
- Spain
- Prior art keywords
- carboxamide
- indole
- alkyl
- benzimidazol
- benzylpiperidinyl
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 123
- 206010019280 Heart failures Diseases 0.000 title claims description 13
- 238000000034 method Methods 0.000 title description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 72
- 125000001424 substituent group Chemical group 0.000 claims abstract description 66
- 125000003118 aryl group Chemical group 0.000 claims abstract description 36
- 125000005843 halogen group Chemical group 0.000 claims abstract description 25
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims abstract description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- -1 3-Cyclohexylmethylamino-2-hydroxypropyl Chemical group 0.000 claims description 57
- 239000002253 acid Substances 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 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 11
- 239000003814 drug Substances 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 230000004044 response Effects 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 5
- GQMYQEAXTITUAE-UHFFFAOYSA-N 1H-indole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=CC2=C1 GQMYQEAXTITUAE-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 208000009525 Myocarditis Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000027418 Wounds and injury Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 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 description 2
- ORTIJHMNUXUBGD-UHFFFAOYSA-N 2-[4-[(2,6-difluorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=C(F)C=CC=C1F ORTIJHMNUXUBGD-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
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- HHWOTKJQXNHRLB-UHFFFAOYSA-N n-[4-benzyl-3-(2,2,2-trifluoroacetyl)piperidin-1-yl]-1h-indole-5-carboxamide Chemical compound FC(F)(F)C(=O)C1CN(NC(=O)C=2C=C3C=CNC3=CC=2)CCC1CC1=CC=CC=C1 HHWOTKJQXNHRLB-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- NJSJBTVAKUBCKG-UHFFFAOYSA-N propylazanide Chemical compound CCC[NH-] NJSJBTVAKUBCKG-UHFFFAOYSA-N 0.000 claims description 2
- 201000004193 respiratory failure Diseases 0.000 claims description 2
- 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
- LWQYPBRPPMFYDQ-UHFFFAOYSA-N 2-[4-(3,4-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(Cl)=C1 LWQYPBRPPMFYDQ-UHFFFAOYSA-N 0.000 claims 1
- FOAXBHNTYFTOTF-UHFFFAOYSA-N 2-[4-(4-chlorobenzoyl)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=C1 FOAXBHNTYFTOTF-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- ZCSUNFCPZFPDKE-UHFFFAOYSA-N 2-[4-[(3,5-difluorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC(F)=CC(F)=C1 ZCSUNFCPZFPDKE-UHFFFAOYSA-N 0.000 claims 1
- DFPYZZWTSGAGDD-UHFFFAOYSA-N 2-[4-[(3-chlorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=CC(Cl)=C1 DFPYZZWTSGAGDD-UHFFFAOYSA-N 0.000 claims 1
- VEBVLTONVCROFJ-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=C(Cl)C=C1 VEBVLTONVCROFJ-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- GZHGTLVTMXEPRL-UHFFFAOYSA-N 2-[4-[(4-methylphenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound C1=CC(C)=CC=C1CN1CCN(C=2NC3=CC(=CC=C3N=2)C(N)=O)CC1 GZHGTLVTMXEPRL-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- GJUCDCMLPQLTFD-UHFFFAOYSA-N 2-[4-[[4-(6-carbamoyl-1h-benzimidazol-2-yl)piperazin-1-yl]methyl]phenyl]acetic acid Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1CC1=CC=C(CC(O)=O)C=C1 GJUCDCMLPQLTFD-UHFFFAOYSA-N 0.000 claims 1
- QEBDNEXNWUHZMH-UHFFFAOYSA-N 2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-3h-benzimidazole-5-carboxamide Chemical compound N1C2=CC(C(=O)N)=CC=C2N=C1N(CC1)CCN1C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 QEBDNEXNWUHZMH-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- KHGINPFZSUAKRV-UHFFFAOYSA-N 4-[(3-chlorophenyl)methyl]-2-piperazin-1-yl-n-propan-2-yl-1h-benzimidazole-5-carboxamide Chemical compound CC(C)NC(=O)C1=CC=C2NC(N3CCNCC3)=NC2=C1CC1=CC=CC(Cl)=C1 KHGINPFZSUAKRV-UHFFFAOYSA-N 0.000 claims 1
- VEMPNDLAIJUTHR-UHFFFAOYSA-N 4-[(3-chlorophenyl)methyl]-n-ethyl-2-piperazin-1-yl-1h-benzimidazole-5-carboxamide Chemical compound CCNC(=O)C1=CC=C2NC(N3CCNCC3)=NC2=C1CC1=CC=CC(Cl)=C1 VEMPNDLAIJUTHR-UHFFFAOYSA-N 0.000 claims 1
- BANJDKJVUNDJPA-UHFFFAOYSA-N 4-[(3-chlorophenyl)methyl]-n-methyl-2-piperazin-1-yl-1h-benzimidazole-5-carboxamide Chemical compound CNC(=O)C1=CC=C2NC(N3CCNCC3)=NC2=C1CC1=CC=CC(Cl)=C1 BANJDKJVUNDJPA-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- VZLYSXDUCUGFBE-UHFFFAOYSA-N 6-chloro-2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-1h-indole-5-carboxamide Chemical compound N1C=2C=C(Cl)C(C(=O)N)=CC=2C=C1N(CC1)CCC1CC1=CC=C(F)C=C1 VZLYSXDUCUGFBE-UHFFFAOYSA-N 0.000 claims 1
- PSADARHBUMRZMR-UHFFFAOYSA-N 7-[(3-chlorophenyl)methyl]-2-piperazin-1-yl-n-propan-2-yl-3h-benzimidazole-5-carboxamide Chemical compound C=12N=C(N3CCNCC3)NC2=CC(C(=O)NC(C)C)=CC=1CC1=CC=CC(Cl)=C1 PSADARHBUMRZMR-UHFFFAOYSA-N 0.000 claims 1
- SXGOSSQXFQPRIB-UHFFFAOYSA-N 7-[(3-chlorophenyl)methyl]-n-ethyl-2-piperazin-1-yl-3h-benzimidazole-5-carboxamide Chemical compound C=12N=C(N3CCNCC3)NC2=CC(C(=O)NCC)=CC=1CC1=CC=CC(Cl)=C1 SXGOSSQXFQPRIB-UHFFFAOYSA-N 0.000 claims 1
- CMNCEUWNPGXTPJ-UHFFFAOYSA-N 7-[(3-chlorophenyl)methyl]-n-methyl-2-piperazin-1-yl-3h-benzimidazole-5-carboxamide Chemical compound C=12N=C(N3CCNCC3)NC2=CC(C(=O)NC)=CC=1CC1=CC=CC(Cl)=C1 CMNCEUWNPGXTPJ-UHFFFAOYSA-N 0.000 claims 1
- 208000009304 Acute Kidney Injury Diseases 0.000 claims 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims 1
- 208000033626 Renal failure acute Diseases 0.000 claims 1
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims 1
- 201000011040 acute kidney failure Diseases 0.000 claims 1
- 208000012998 acute renal failure Diseases 0.000 claims 1
- 206010001053 acute respiratory failure Diseases 0.000 claims 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- TWGLCYRIADFYJW-UHFFFAOYSA-N n-benzyl-4-[(3-chlorophenyl)methyl]-2-piperazin-1-yl-1h-benzimidazole-5-carboxamide Chemical compound ClC1=CC=CC(CC=2C=3N=C(NC=3C=CC=2C(=O)NCC=2C=CC=CC=2)N2CCNCC2)=C1 TWGLCYRIADFYJW-UHFFFAOYSA-N 0.000 claims 1
- FWRGJBLNQBPDRQ-UHFFFAOYSA-N n-benzyl-7-[(3-chlorophenyl)methyl]-2-piperazin-1-yl-3h-benzimidazole-5-carboxamide Chemical compound ClC1=CC=CC(CC=2C=3N=C(NC=3C=C(C=2)C(=O)NCC=2C=CC=CC=2)N2CCNCC2)=C1 FWRGJBLNQBPDRQ-UHFFFAOYSA-N 0.000 claims 1
- 239000008896 Opium Substances 0.000 abstract 1
- 229960001027 opium Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000000203 mixture Substances 0.000 description 53
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 37
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- 239000000243 solution Substances 0.000 description 31
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 27
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 26
- 239000000284 extract Substances 0.000 description 23
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- 230000000694 effects Effects 0.000 description 19
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- 239000000758 substrate Substances 0.000 description 7
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Classifications
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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
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8653198P | 1998-05-22 | 1998-05-22 | |
| US86531P | 1998-05-22 | ||
| US128137 | 1998-08-03 | ||
| US09/128,137 US6130235A (en) | 1998-05-22 | 1998-08-03 | Compounds and methods to treat cardiac failure and other disorders |
| US275176 | 1999-03-24 | ||
| US09/275,176 US6340685B1 (en) | 1998-05-22 | 1999-03-24 | Compounds and methods to treat cardiac failure and other disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2258331T3 true ES2258331T3 (es) | 2006-08-16 |
Family
ID=46203611
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99924412T Expired - Lifetime ES2258331T3 (es) | 1998-05-22 | 1999-05-21 | Compuestos heterociclicos y procedimientos de tratamiento de insuficiencia cardiaca y otros trastornos. |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1080078B1 (https=) |
| JP (1) | JP2002516314A (https=) |
| KR (1) | KR100605140B1 (https=) |
| CN (1) | CN1229351C (https=) |
| AT (1) | ATE316961T1 (https=) |
| AU (2) | AU769465B2 (https=) |
| BR (1) | BR9911069A (https=) |
| CA (1) | CA2332459A1 (https=) |
| DE (1) | DE69929689T2 (https=) |
| ES (1) | ES2258331T3 (https=) |
| HU (1) | HUP0203657A3 (https=) |
| NO (1) | NO320299B1 (https=) |
| NZ (1) | NZ508790A (https=) |
| PL (1) | PL346345A1 (https=) |
| WO (1) | WO1999061426A1 (https=) |
Families Citing this family (56)
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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 |
| CA2342251A1 (en) * | 1998-08-28 | 2000-03-09 | Scios Inc. | Use of piperidines and/or piperazines as inhibitors of p38-alpha kinase |
| WO2000025791A1 (en) | 1998-11-04 | 2000-05-11 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
| JP2003500403A (ja) * | 1999-05-21 | 2003-01-07 | サイオス，インコーポレーテッド | ｐ３８キナーゼのインヒビターとしてのインドール型誘導体 |
| IL146309A (en) | 1999-05-21 | 2008-03-20 | Scios Inc | Derivatives of the indole type and pharmaceutical preparations containing them as inhibitors of kinase p38 |
| RU2278115C2 (ru) * | 1999-05-21 | 2006-06-20 | Сайос Инк. | ПРОИЗВОДНЫЕ ИНДОЛЬНОГО РЯДА В КАЧЕСТВЕ ИНГИБИТОРОВ p38 КИНАЗЫ |
| US6541477B2 (en) | 1999-08-27 | 2003-04-01 | Scios, Inc. | Inhibitors of p38-a kinase |
| EP1233951B1 (en) | 1999-11-23 | 2005-06-01 | SmithKline Beecham Corporation | 3,4-dihydro-(1h)quinazolin-2-one compounds as csbp/p38 kinase inhibitors |
| AU1781601A (en) | 1999-11-23 | 2001-06-04 | Smithkline Beecham Corporation | 3,4-dihydro-(1h)quinazolin-2-one compounds as csbp/p38 kinase inhibitors |
| ATE305787T1 (de) | 1999-11-23 | 2005-10-15 | Smithkline Beecham Corp | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p39-kinase-inhibitoren |
| US6372752B1 (en) * | 2000-02-07 | 2002-04-16 | Genzyme Corporation | Inha inhibitors and methods of use thereof |
| AU2001241927A1 (en) * | 2000-02-28 | 2001-09-12 | Scios Inc. | Inhibitors of p38-alpha kinase |
| US7235551B2 (en) | 2000-03-02 | 2007-06-26 | Smithkline Beecham Corporation | 1,5-disubstituted-3,4-dihydro-1h-pyrimido[4,5-d]pyrimidin-2-one compounds and their use in treating csbp/p38 kinase mediated diseases |
| EP1322309B1 (en) * | 2000-09-29 | 2008-08-13 | Neurogen Corporation | High affinity small molecule c5a receptor modulators |
| DE60125980T2 (de) | 2000-11-20 | 2007-10-25 | Scios Inc., Sunnyvale | P38kinase-inhibitoren vom piperidin/piperazin-typ |
| WO2002044168A2 (en) * | 2000-11-20 | 2002-06-06 | Scios Inc. | Indole-type inhibitors of p38 kinase |
| EP1341782A2 (en) | 2000-11-20 | 2003-09-10 | Scios Inc. | Inhibitors of p38 kinase |
| TR200401028T2 (tr) * | 2001-11-09 | 2004-11-22 | Scios Inc. | Kistik fibrozun tedavisine yönelik metot |
| US20030225089A1 (en) * | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
| DE60310730T2 (de) | 2002-07-09 | 2007-05-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmazeutische zusammensetzungen aus anticholinergica und p38 kinase hemmern zur behandlung von erkrankungen der atemwege |
| CA2497408A1 (en) | 2002-09-03 | 2004-03-18 | Sarvajit Chakravarty | Indole-type derivatives as inhibitors of p38 kinase |
| EP1560582A4 (en) | 2002-10-09 | 2008-03-12 | Scios Inc | AZAINDOL DERIVATIVES AS INHIBITORS OF THE p38 KINASE |
| CN101039957A (zh) | 2003-05-16 | 2007-09-19 | 因特缪恩公司 | 合成的趋化因子受体配体及其使用方法 |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| GB0318814D0 (en) | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| BRPI0413595B8 (pt) * | 2003-08-18 | 2021-05-25 | H Lundbeck As | sal de malonato, composição farmacêutica, uso de um sal de malonato, e, método de fabricação de um composto |
| US7244441B2 (en) | 2003-09-25 | 2007-07-17 | Scios, Inc. | Stents and intra-luminal prostheses containing map kinase inhibitors |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| EP1833819A1 (en) | 2004-12-30 | 2007-09-19 | Astex Therapeutics Limited | Pyrazole compounds that modulate the activity of cdk, gsk and aurora kinases |
| TWI376373B (en) | 2005-02-16 | 2012-11-11 | Lundbeck & Co As H | Crystalline base of a pharmaceutical compound |
| TWI453198B (zh) | 2005-02-16 | 2014-09-21 | Lundbeck & Co As H | 製造反式-1-((1r,3s)-6-氯基-3-苯基茚滿-1-基) -3 , 3 -二甲基六氫吡與其鹽類之方法及製造4-((1r , 3s）-6 -氯基-3-苯基茚滿-1-基 )-1,2,2-三甲基六氫吡與其鹽類之方法 |
| EP1953148B1 (en) | 2005-10-28 | 2012-02-29 | Takeda Pharmaceutical Company Limited | Heterocyclic amide compound and use thereof |
| US7977359B2 (en) | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
| GB2431927B (en) * | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
| US8399666B2 (en) | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| EP1968579A1 (en) | 2005-12-30 | 2008-09-17 | Astex Therapeutics Limited | Pharmaceutical compounds |
| EP2520567A3 (en) * | 2006-02-23 | 2012-12-12 | Shionogi & Co., Ltd. | Nitrogen-containing heterocycle derivatives substituted with cyclic group |
| EP2049119A2 (en) | 2006-06-29 | 2009-04-22 | Astex Therapeutics Limited | Pharmaceutical combinations of 1-cyclopropyl-3-[3-(5-morphoolin-4-ylmethyl-1h-benzoimidazol-2-yl)-1h-1-pyrazol-4-yl]-urea |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| JP5894161B2 (ja) * | 2010-08-25 | 2016-03-23 | ネオファーム カンパニー， リミテッド | 新規の複素環化合物及びこれを用いた炎症性疾患治療用組成物 |
| KR101421032B1 (ko) * | 2012-12-28 | 2014-07-22 | 주식회사 레고켐 바이오사이언스 | (2-메틸-1-(3-메틸벤질)-1Ｈ-벤조[d]이미다졸-5일)(피페리딘-5-일)메탄온의 제조방법 |
| GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| WO2019071147A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | INHIBITORS OF KINASE P38 REDUCING EXPRESSION OF DUX4 GENE AND DOWNSTREAM GENES FOR THE TREATMENT OF FSHD |
| WO2019075386A1 (en) * | 2017-10-13 | 2019-04-18 | The Regents Of The University Of California | MODULATORS OF MTORC1 |
| JP2025530213A (ja) | 2022-09-09 | 2025-09-11 | ミリックス ファーマ リミテッド | Ｎｍｔ阻害剤を含む抗体薬物コンジュゲート及びその使用 |
| CN118546081A (zh) * | 2023-02-27 | 2024-08-27 | 上海交通大学 | 一类肉桂酰胺衍生物及其应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179505A (en) * | 1977-03-30 | 1979-12-18 | Janssen Pharmaceutica N.V. | 5-[4-(Diarylmethyl)-1-piperazinylalkyl]benzimidazole derivatives |
| EP0318235A3 (en) * | 1987-11-25 | 1991-05-02 | Takeda Chemical Industries, Ltd. | Paf antagonist, 1,4-disubstituted piperazine compounds and production thereof |
| JPH01230570A (ja) * | 1987-11-25 | 1989-09-14 | Takeda Chem Ind Ltd | 抗ｐａｆ剤および１，４−ジ置換ピペラジン化合物 |
| US5032598A (en) * | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Nitrogens containing heterocyclic compounds as class III antiarrhythmic agents |
| ATE174915T1 (de) * | 1994-10-31 | 1999-01-15 | Merck Patent Gmbh | Benzylpiperidinderivate mit hoher affinität zu bindungsstellen von aminosäure-rezeptoren |
| EP0922042A1 (en) * | 1996-08-09 | 1999-06-16 | Smithkline Beecham Corporation | Novel piperazine containing compounds |
| FR2753706B1 (fr) * | 1996-09-20 | 1998-10-30 | Nouvelles amines cycliques n-substituees, leur procede de preparation et les compositions pharmaceutiques les renfermant | |
| 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
- 1999-05-21 ES ES99924412T patent/ES2258331T3/es not_active Expired - Lifetime
- 1999-05-21 PL PL99346345A patent/PL346345A1/xx not_active IP Right Cessation
- 1999-05-21 CA CA002332459A patent/CA2332459A1/en not_active Abandoned
- 1999-05-21 DE DE69929689T patent/DE69929689T2/de not_active Expired - Fee Related
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2000
- 2000-11-21 NO NO20005881A patent/NO320299B1/no unknown
-
2004
- 2004-04-29 AU AU2004201809A patent/AU2004201809A1/en not_active Abandoned
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 |
| AU769465B2 (en) | 2004-01-29 |
| BR9911069A (pt) | 2001-02-06 |
| AU4092099A (en) | 1999-12-13 |
| NO20005881D0 (no) | 2000-11-21 |
| NZ508790A (en) | 2003-10-31 |
| 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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