CA2362862A1 - Bicyclic compounds and their use as integrin receptor ligands - Google Patents
Bicyclic compounds and their use as integrin receptor ligands Download PDFInfo
- Publication number
- CA2362862A1 CA2362862A1 CA002362862A CA2362862A CA2362862A1 CA 2362862 A1 CA2362862 A1 CA 2362862A1 CA 002362862 A CA002362862 A CA 002362862A CA 2362862 A CA2362862 A CA 2362862A CA 2362862 A1 CA2362862 A1 CA 2362862A1
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- CA
- Canada
- Prior art keywords
- alkyl
- compounds
- optionally substituted
- compound according
- formula
- 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.)
- Abandoned
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- 125000002619 bicyclic group Chemical group 0.000 title abstract description 5
- 108010044426 integrins Proteins 0.000 title description 20
- 102000006495 integrins Human genes 0.000 title description 20
- 239000003446 ligand Substances 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 232
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 239000001257 hydrogen Substances 0.000 claims abstract description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
- 229940002612 prodrug Drugs 0.000 claims abstract description 30
- 239000000651 prodrug Substances 0.000 claims abstract description 30
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 22
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 20
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 17
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical group 0.000 claims abstract description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
- 125000004419 alkynylene group Chemical group 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 81
- -1 arylsulphinyl Chemical group 0.000 claims description 72
- 238000000034 method Methods 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 25
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 230000021164 cell adhesion Effects 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 230000001668 ameliorated effect Effects 0.000 claims description 6
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 5
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 5
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 4
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 4
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000005239 aroylamino group Chemical group 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 2
- 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 239000002253 acid Chemical group 0.000 abstract description 46
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 abstract description 18
- 108010067306 Fibronectins Proteins 0.000 abstract description 13
- 102000016359 Fibronectins Human genes 0.000 abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 abstract description 10
- 150000004677 hydrates Chemical class 0.000 abstract description 9
- 230000003993 interaction Effects 0.000 abstract description 9
- 125000000732 arylene group Chemical group 0.000 abstract description 4
- 125000002993 cycloalkylene group Chemical group 0.000 abstract description 3
- 125000006588 heterocycloalkylene group Chemical group 0.000 abstract description 3
- 108010008212 Integrin alpha4beta1 Proteins 0.000 abstract 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 150000002148 esters Chemical class 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 125000001309 chloro group Chemical group Cl* 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 239000011347 resin Substances 0.000 description 15
- 229920005989 resin Polymers 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 238000000105 evaporative light scattering detection Methods 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000006978 adaptation Effects 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 125000001931 aliphatic group Chemical group 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 6
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 6
- JMMZYEHPYZGZOK-SECBINFHSA-N ethyl (3r)-3-(4-aminophenyl)butanoate Chemical compound CCOC(=O)C[C@@H](C)C1=CC=C(N)C=C1 JMMZYEHPYZGZOK-SECBINFHSA-N 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
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- 239000012948 isocyanate Substances 0.000 description 6
- 150000002513 isocyanates Chemical class 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
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- 125000001424 substituent group Chemical group 0.000 description 6
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- JYKYYPPZLPVIBY-UHFFFAOYSA-N 1-isothiocyanato-2-methylbenzene Chemical compound CC1=CC=CC=C1N=C=S JYKYYPPZLPVIBY-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
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- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9903532.1 | 1999-02-16 | ||
| GBGB9903532.1A GB9903532D0 (en) | 1999-02-16 | 1999-02-16 | Chemical compounds |
| US14144599P | 1999-06-29 | 1999-06-29 | |
| US60/141,445 | 1999-06-29 | ||
| PCT/GB2000/000553 WO2000049005A1 (en) | 1999-02-16 | 2000-02-16 | Bicyclic compounds and their use as integrin receptor ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2362862A1 true CA2362862A1 (en) | 2000-08-24 |
Family
ID=26315145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002362862A Abandoned CA2362862A1 (en) | 1999-02-16 | 2000-02-16 | Bicyclic compounds and their use as integrin receptor ligands |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6593354B2 (enExample) |
| EP (1) | EP1153017B1 (enExample) |
| JP (1) | JP2002537292A (enExample) |
| AT (1) | ATE325105T1 (enExample) |
| AU (1) | AU775208B2 (enExample) |
| CA (1) | CA2362862A1 (enExample) |
| DE (1) | DE60027700T2 (enExample) |
| DK (1) | DK1153017T3 (enExample) |
| ES (1) | ES2263447T3 (enExample) |
| PT (1) | PT1153017E (enExample) |
| WO (1) | WO2000049005A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0010599A (pt) * | 1999-04-12 | 2002-02-13 | Aventis Pharma Ltd | Compostos de heteroarila bicìclicos substituìdos como antagonistas de integrina |
| GB9908355D0 (en) * | 1999-04-12 | 1999-06-09 | Rhone Poulenc Rorer Ltd | Chemical compounds |
| GB0001346D0 (en) * | 2000-01-21 | 2000-03-08 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004686D0 (en) * | 2000-02-28 | 2000-04-19 | Aventis Pharma Ltd | Chemical compounds |
| US7157487B2 (en) | 2000-12-28 | 2007-01-02 | Daiichi Pharmaceutical Co., Ltd. | Vla-4 inhibitors |
| US7351719B2 (en) | 2002-10-31 | 2008-04-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Amide compounds having MCH-antagonistic activity and medicaments comprising these compounds |
| ES2382806T3 (es) | 2003-07-24 | 2012-06-13 | Daiichi Sankyo Company, Limited | Compuesto ácido ciclohexanocarboxílico |
| US7592373B2 (en) | 2003-12-23 | 2009-09-22 | Boehringer Ingelheim International Gmbh | Amide compounds with MCH antagonistic activity and medicaments comprising these compounds |
| DE10360745A1 (de) * | 2003-12-23 | 2005-07-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Amid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| BRPI0508098A (pt) * | 2004-02-27 | 2007-07-17 | Amgen Inc | compostos, composições farmacêuticas e métodos para uso no tratamento de distúrbios metabólicos |
| US7524862B2 (en) | 2004-04-14 | 2009-04-28 | Boehringer Ingelheim International Gmbh | Alkyne compounds with MCH antagonistic activity and medicaments comprising these compounds |
| DE102004017934A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| US20070021612A1 (en) * | 2004-11-04 | 2007-01-25 | University Of Notre Dame Du Lac | Processes and compounds for preparing histone deacetylase inhibitors and intermediates thereof |
| US7235688B1 (en) | 2004-11-04 | 2007-06-26 | University Of Notre Dame Du Lac | Process for preparing histone deacetylase inhibitors and intermediates thereof |
| DE102006021878A1 (de) | 2006-05-11 | 2007-11-15 | Sanofi-Aventis | Phenylamino-benzoxazol substituierte Carbonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| UY32138A (es) * | 2008-09-25 | 2010-04-30 | Boehringer Ingelheim Int | Amidas sustituidas del ácido 2-(2,6-dicloro-fenilamino)-6-fluoro-1-metil-1h-bencimidazol-5-carboxílico y sus sales farmacéuticamente aceptables |
| UY32470A (es) | 2009-03-05 | 2010-10-29 | Boehringer Ingelheim Int | Derivados de 2-{2-cloro-5-[(sustituido) metil]fenilamino} -1-metil]fenilamino}-1-metilbencimidazol-5-carboxamidas-n-(sustituidas) y sus sales fisiológicamente aceptables, composiciones conteniéndolos y aplicaciones |
| US8586604B2 (en) | 2010-08-20 | 2013-11-19 | Boehringer Ingelheim International Gmbh | Inhibitors of the microsomal prostaglandin E2 synthase-1 |
| US8759537B2 (en) | 2010-08-20 | 2014-06-24 | Boehringer Ingelheim International Gmbh | 3H-imidazo [4, 5-C] pyridine-6-carboxamides as anti-inflammatory agents |
| US8674113B2 (en) | 2010-12-10 | 2014-03-18 | Boehringer Ingelheim International Gmbh | Compounds |
| US8466186B2 (en) | 2010-12-10 | 2013-06-18 | Boehringer Ingelheim International Gmbh | Compounds |
| US8486968B2 (en) | 2010-12-10 | 2013-07-16 | Boehringer Ingelheim International Gmbh | Compounds |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4025637A (en) | 1973-10-23 | 1977-05-24 | Lilly Industries, Ltd. | 2,5 OR 2,6 Disubstituted benzoxazoles |
| US4100168A (en) | 1974-09-20 | 1978-07-11 | Lilly Industries Ltd. | 2,5 OR 2,6-Disubstituted benzoxazoles |
| US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
| PT889877E (pt) * | 1996-03-29 | 2002-02-28 | Searle & Co | Derivados fenileno meta substituidos e sua utilizacao como antagonitas ou inibidores integrina alfa v beta3 |
| JPH10330369A (ja) | 1997-04-04 | 1998-12-15 | Sumitomo Pharmaceut Co Ltd | 複素環化合物 |
| GB9723789D0 (en) | 1997-11-12 | 1998-01-07 | Zeneca Ltd | Chemical compounds |
| GB9916374D0 (en) * | 1998-07-23 | 1999-09-15 | Zeneca Ltd | Chemical compounds |
| WO2000005223A2 (en) * | 1998-07-23 | 2000-02-03 | Astrazeneca Ab | Heterocyclic derivatives and their use as integrin inhibitors |
-
2000
- 2000-02-16 EP EP00903864A patent/EP1153017B1/en not_active Expired - Lifetime
- 2000-02-16 AT AT00903864T patent/ATE325105T1/de not_active IP Right Cessation
- 2000-02-16 DE DE60027700T patent/DE60027700T2/de not_active Expired - Fee Related
- 2000-02-16 DK DK00903864T patent/DK1153017T3/da active
- 2000-02-16 CA CA002362862A patent/CA2362862A1/en not_active Abandoned
- 2000-02-16 PT PT00903864T patent/PT1153017E/pt unknown
- 2000-02-16 ES ES00903864T patent/ES2263447T3/es not_active Expired - Lifetime
- 2000-02-16 AU AU25617/00A patent/AU775208B2/en not_active Ceased
- 2000-02-16 WO PCT/GB2000/000553 patent/WO2000049005A1/en not_active Ceased
- 2000-02-16 JP JP2000599745A patent/JP2002537292A/ja active Pending
-
2001
- 2001-08-09 US US09/925,110 patent/US6593354B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1153017A1 (en) | 2001-11-14 |
| DE60027700T2 (de) | 2007-05-03 |
| PT1153017E (pt) | 2006-07-31 |
| ATE325105T1 (de) | 2006-06-15 |
| DE60027700D1 (de) | 2006-06-08 |
| EP1153017B1 (en) | 2006-05-03 |
| AU2561700A (en) | 2000-09-04 |
| US20020137782A1 (en) | 2002-09-26 |
| US6593354B2 (en) | 2003-07-15 |
| JP2002537292A (ja) | 2002-11-05 |
| WO2000049005A1 (en) | 2000-08-24 |
| AU775208B2 (en) | 2004-07-22 |
| DK1153017T3 (da) | 2006-07-17 |
| ES2263447T3 (es) | 2006-12-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |