ES2296926T3 - Tetrahidroisoquinolinas sustituidas para usar en el tratamiento de enfermedades inflamatorias. - Google Patents
Tetrahidroisoquinolinas sustituidas para usar en el tratamiento de enfermedades inflamatorias. Download PDFInfo
- Publication number
- ES2296926T3 ES2296926T3 ES02730462T ES02730462T ES2296926T3 ES 2296926 T3 ES2296926 T3 ES 2296926T3 ES 02730462 T ES02730462 T ES 02730462T ES 02730462 T ES02730462 T ES 02730462T ES 2296926 T3 ES2296926 T3 ES 2296926T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- alkyl
- optionally substituted
- compound according
- aryl
- 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
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- 238000011282 treatment Methods 0.000 title claims description 33
- 208000027866 inflammatory disease Diseases 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 239
- -1 cycloalkenyl alkyl Chemical group 0.000 claims abstract description 155
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 132
- 239000002253 acid Substances 0.000 claims abstract description 93
- 125000003118 aryl group Chemical group 0.000 claims abstract description 91
- 239000001257 hydrogen Substances 0.000 claims abstract description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 77
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 150000002148 esters Chemical class 0.000 claims abstract description 51
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 46
- 229940002612 prodrug Drugs 0.000 claims abstract description 46
- 239000000651 prodrug Substances 0.000 claims abstract description 46
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 35
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 30
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 28
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
- 239000012453 solvate Substances 0.000 claims abstract description 25
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 21
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 20
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- 125000000524 functional group Chemical group 0.000 claims abstract description 16
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 15
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- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
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- 239000000203 mixture Substances 0.000 claims description 61
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
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- 239000005977 Ethylene Substances 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 14
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- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 10
- 125000004098 2,6-dichlorobenzoyl group Chemical group O=C([*])C1=C(Cl)C([H])=C([H])C([H])=C1Cl 0.000 claims description 9
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- VYKZWLFZJMDXPY-UHFFFAOYSA-N 3-[2-[2-[3-methoxy-4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]-3,4-dihydro-1h-isoquinolin-8-yl]butanoic acid Chemical compound COC1=CC(CC(=O)N2CC3=C(C(C)CC(O)=O)C=CC=C3CC2)=CC=C1NC(=O)NC1=CC=CC=C1C VYKZWLFZJMDXPY-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
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- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 5
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- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical group NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
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- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims 3
- 150000001555 benzenes Chemical group 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 10
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 238000000034 method Methods 0.000 description 42
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- 125000004494 ethyl ester group Chemical group 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
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- 150000004677 hydrates Chemical class 0.000 description 13
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0113708A GB0113708D0 (en) | 2001-06-06 | 2001-06-06 | Chemical compounds |
| GB0113708 | 2001-06-06 | ||
| US31150201P | 2001-08-10 | 2001-08-10 | |
| US311502P | 2001-08-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2296926T3 true ES2296926T3 (es) | 2008-05-01 |
Family
ID=26246159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02730462T Expired - Lifetime ES2296926T3 (es) | 2001-06-06 | 2002-06-05 | Tetrahidroisoquinolinas sustituidas para usar en el tratamiento de enfermedades inflamatorias. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7211586B2 (enExample) |
| EP (1) | EP1392306B1 (enExample) |
| JP (1) | JP4583751B2 (enExample) |
| AT (1) | ATE383858T1 (enExample) |
| AU (1) | AU2002302783B2 (enExample) |
| CA (1) | CA2449402C (enExample) |
| DE (1) | DE60224664T2 (enExample) |
| DK (1) | DK1392306T3 (enExample) |
| ES (1) | ES2296926T3 (enExample) |
| IL (1) | IL159203A0 (enExample) |
| MX (1) | MXPA03009660A (enExample) |
| PT (1) | PT1392306E (enExample) |
| WO (1) | WO2002098426A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004287875B2 (en) | 2003-11-05 | 2011-06-02 | Bausch + Lomb Ireland Limited | Modulators of cellular adhesion |
| WO2005070891A2 (en) * | 2004-01-23 | 2005-08-04 | Amgen Inc | Compounds and methods of use |
| JP2006056830A (ja) * | 2004-08-20 | 2006-03-02 | Dai Ichi Seiyaku Co Ltd | ２−アリールアミノベンゾオキサゾール誘導体 |
| ES2450566T3 (es) | 2004-11-30 | 2014-03-25 | Amgen Inc. | Análogos de quinazolina y quinolinas y su uso como medicamentos para tratar el cáncer |
| US7297700B2 (en) * | 2005-03-24 | 2007-11-20 | Renovis, Inc. | Bicycloheteroaryl compounds as P2X7 modulators and uses thereof |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| WO2006125119A1 (en) | 2005-05-17 | 2006-11-23 | Sarcode Corporation | Compositions and methods for treatment of eye disorders |
| WO2007050124A1 (en) * | 2005-05-19 | 2007-05-03 | Xenon Pharmaceuticals Inc. | Fused piperidine derivatives and their uses as therapeutic agents |
| CN101873797A (zh) | 2007-10-19 | 2010-10-27 | 萨可德公司 | 用于治疗糖尿病性视网膜病的组合物和方法 |
| EP3632444A3 (en) * | 2008-04-15 | 2020-08-26 | SARcode Bioscience Inc. | Topical lfa-1 antagonists for use in localized treatment of immune related disorders |
| US20090257957A1 (en) * | 2008-04-15 | 2009-10-15 | John Burnier | Aerosolized LFA-1 antagonists for use in localized treatment of immune related disorders |
| EP2276508A4 (en) * | 2008-04-15 | 2011-12-28 | Sarcode Bioscience Inc | ADMINISTRATION OF LFA-1 ANTAGONISTS TO THE GASTROINTESTINAL SYSTEM |
| US8080562B2 (en) | 2008-04-15 | 2011-12-20 | Sarcode Bioscience Inc. | Crystalline pharmaceutical and methods of preparation and use thereof |
| US8324384B2 (en) | 2009-02-12 | 2012-12-04 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| WO2011050175A1 (en) | 2009-10-21 | 2011-04-28 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
| AU2012322095B2 (en) * | 2011-10-14 | 2017-06-29 | Ambit Biosciences Corporation | Heterocyclic compounds and use thereof as modulators of type III receptor tyrosine kinases |
| BR112014012997A2 (pt) * | 2011-11-30 | 2017-06-13 | Bikam Pharmaceuticals Inc | ligantes que se ligam à opsina, composições e métodos de uso |
| EP4406950A3 (en) | 2012-07-25 | 2025-04-23 | Bausch + Lomb Ireland Limited | Lfa-1 inhibitor and polymorph thereof |
| EP3573968A1 (en) * | 2017-01-30 | 2019-12-04 | Biogen MA Inc. | Nrf2 activator |
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| WO2023287241A1 (ko) * | 2021-07-15 | 2023-01-19 | 주식회사 휴사이온 | 신규한 벤즈옥사졸아민 유도체 화합물 및 이를 포함하는 암의 예방 또는 치료용 약학 조성물 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5236934A (en) * | 1992-08-26 | 1993-08-17 | E. I. Du Pont De Nemours And Company | 1,2,3,4-tetrahydroisoquinolines useful in the treatment of CNS disorders |
| EA004792B1 (ru) * | 1998-06-30 | 2004-08-26 | Пфайзер Продактс Инк. | Непептидные ингибиторы vla-4-зависимого клеточного связывания, полезные в лечении воспалительных, аутоиммунных и респираторных заболеваний |
| DE69934238T2 (de) * | 1998-08-26 | 2007-06-21 | Aventis Pharma Ltd., West Malling | Azabicyclo-verbindungen welche die inhibition der zell adhesion modulieren |
| US6469047B1 (en) * | 1999-09-24 | 2002-10-22 | Genentech, Inc. | Tyrosine derivatives |
-
2002
- 2002-06-05 MX MXPA03009660A patent/MXPA03009660A/es unknown
- 2002-06-05 PT PT02730462T patent/PT1392306E/pt unknown
- 2002-06-05 IL IL15920302A patent/IL159203A0/xx unknown
- 2002-06-05 ES ES02730462T patent/ES2296926T3/es not_active Expired - Lifetime
- 2002-06-05 AT AT02730462T patent/ATE383858T1/de not_active IP Right Cessation
- 2002-06-05 JP JP2003501465A patent/JP4583751B2/ja not_active Expired - Fee Related
- 2002-06-05 CA CA002449402A patent/CA2449402C/en not_active Expired - Fee Related
- 2002-06-05 AU AU2002302783A patent/AU2002302783B2/en not_active Ceased
- 2002-06-05 DE DE60224664T patent/DE60224664T2/de not_active Expired - Lifetime
- 2002-06-05 DK DK02730462T patent/DK1392306T3/da active
- 2002-06-05 WO PCT/GB2002/002517 patent/WO2002098426A1/en not_active Ceased
- 2002-06-05 EP EP02730462A patent/EP1392306B1/en not_active Expired - Lifetime
-
2003
- 2003-11-18 US US10/715,662 patent/US7211586B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60224664T2 (de) | 2009-01-08 |
| PT1392306E (pt) | 2008-03-07 |
| US7211586B2 (en) | 2007-05-01 |
| EP1392306B1 (en) | 2008-01-16 |
| DE60224664D1 (de) | 2008-03-06 |
| JP2005500276A (ja) | 2005-01-06 |
| EP1392306A1 (en) | 2004-03-03 |
| IL159203A0 (en) | 2004-06-01 |
| JP4583751B2 (ja) | 2010-11-17 |
| ATE383858T1 (de) | 2008-02-15 |
| CA2449402C (en) | 2009-08-11 |
| MXPA03009660A (es) | 2004-04-02 |
| US20040122047A1 (en) | 2004-06-24 |
| DK1392306T3 (da) | 2008-05-19 |
| CA2449402A1 (en) | 2002-12-12 |
| WO2002098426A1 (en) | 2002-12-12 |
| AU2002302783B2 (en) | 2006-11-16 |
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