RU2348630C2 - Производные 2-ациламино-4-фенилтиазола, их получение и их применение в терапии - Google Patents
Производные 2-ациламино-4-фенилтиазола, их получение и их применение в терапии Download PDFInfo
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- RU2348630C2 RU2348630C2 RU2005136663/04A RU2005136663A RU2348630C2 RU 2348630 C2 RU2348630 C2 RU 2348630C2 RU 2005136663/04 A RU2005136663/04 A RU 2005136663/04A RU 2005136663 A RU2005136663 A RU 2005136663A RU 2348630 C2 RU2348630 C2 RU 2348630C2
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- alkyl
- compound
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- 238000002560 therapeutic procedure Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- -1 (C1-C4)-alkoxyl Chemical group 0.000 claims abstract description 120
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
- 125000005843 halogen group Chemical group 0.000 claims abstract description 17
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 9
- 102000019034 Chemokines Human genes 0.000 claims abstract description 9
- 108010012236 Chemokines Proteins 0.000 claims abstract description 9
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 150000007513 acids Chemical class 0.000 claims description 10
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 9
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 9
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 239000005557 antagonist Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical group NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000002559 chemokine receptor antagonist Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 206010020751 Hypersensitivity Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 208000026935 allergic disease Diseases 0.000 abstract description 3
- 230000003042 antagnostic effect Effects 0.000 abstract description 3
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 2
- 230000007815 allergy Effects 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract description 2
- 230000000495 immunoinflammatory effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 230
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 138
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 112
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 76
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 56
- 235000019341 magnesium sulphate Nutrition 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 55
- 239000002609 medium Substances 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- 239000000203 mixture Substances 0.000 description 50
- 239000012074 organic phase Substances 0.000 description 42
- 238000002360 preparation method Methods 0.000 description 39
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- 239000007787 solid Substances 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 239000011734 sodium Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000003756 stirring Methods 0.000 description 24
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000010586 diagram Methods 0.000 description 21
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 18
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 18
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
- 239000012429 reaction media Substances 0.000 description 18
- 229940086542 triethylamine Drugs 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 239000002243 precursor Substances 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 11
- 239000012047 saturated solution Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 description 7
- 125000005336 allyloxy group Chemical group 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 238000010908 decantation Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 0 CO*(CC1)CCC1=O Chemical compound CO*(CC1)CCC1=O 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- MHSKRLJMQQNJNC-UHFFFAOYSA-N terephthalamide Chemical compound NC(=O)C1=CC=C(C(N)=O)C=C1 MHSKRLJMQQNJNC-UHFFFAOYSA-N 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- REIDAMBAPLIATC-UHFFFAOYSA-N 4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-N 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 229950003476 aminothiazole Drugs 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
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- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
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- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- 102000004497 CCR2 Receptors Human genes 0.000 description 3
- 108010017312 CCR2 Receptors Proteins 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 3
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- 229910052740 iodine Inorganic materials 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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- ZDMUWEXQZFRIMB-UHFFFAOYSA-N n-[4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-yl]-4-(2-oxoethoxy)benzamide Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(OCC=O)=CC=3)SC=2)=C1 ZDMUWEXQZFRIMB-UHFFFAOYSA-N 0.000 description 3
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- 238000003786 synthesis reaction Methods 0.000 description 3
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- OYAYJSSZNWHFQH-UHFFFAOYSA-N 1-methoxy-4-(1,1,2,2,2-pentafluoroethyl)benzene Chemical compound COC1=CC=C(C(F)(F)C(F)(F)F)C=C1 OYAYJSSZNWHFQH-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- GYLMCBOAXJVARF-UHFFFAOYSA-N 3-azabicyclo[2.2.1]heptane Chemical compound C1C2CCC1NC2 GYLMCBOAXJVARF-UHFFFAOYSA-N 0.000 description 2
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 description 2
- NWLFUZQESWFKGV-UHFFFAOYSA-N 4-(2,2-diethoxyethoxy)benzoic acid Chemical compound CCOC(OCC)COC1=CC=C(C(O)=O)C=C1 NWLFUZQESWFKGV-UHFFFAOYSA-N 0.000 description 2
- GMAACCYBQHHVDO-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-n-[4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-yl]benzamide Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(NC(=O)C=3C=CC(OCCO)=CC=3)SC=2)=C1 GMAACCYBQHHVDO-UHFFFAOYSA-N 0.000 description 2
- KEMBKBIOSMRWAA-UHFFFAOYSA-N 4-(2-methoxy-5-propoxyphenyl)-1,3-thiazol-2-amine Chemical compound CCCOC1=CC=C(OC)C(C=2N=C(N)SC=2)=C1 KEMBKBIOSMRWAA-UHFFFAOYSA-N 0.000 description 2
- ACNPMHHSEMHUGY-UHFFFAOYSA-N 4-(5-butyl-2-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound CCCCC1=CC=C(OC)C(C=2N=C(N)SC=2)=C1 ACNPMHHSEMHUGY-UHFFFAOYSA-N 0.000 description 2
- HZXWLKUJDKRBQF-UHFFFAOYSA-N 4-(5-cyclohexyl-2-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound COC1=CC=C(C2CCCCC2)C=C1C1=CSC(N)=N1 HZXWLKUJDKRBQF-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2576036C2 (ru) * | 2010-03-17 | 2016-02-27 | Тайвекс Терапьютикс Корпорейшн | Модуляторы активности нес1 и способы для них |
| US11071736B2 (en) | 2011-11-21 | 2021-07-27 | Taivex Therapeutics Corporation | Modulators of HEC1 activity and methods therefor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JO2676B1 (en) * | 2004-04-06 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Derivatives of second-aza-spiro- (5,4) -dikan and their use as antihistamines |
| JO2527B1 (en) * | 2004-04-06 | 2010-03-17 | شركة جانسين فارماسوتيكا ان. في | Derivatives of second-aza-Spiro- (5,5) -andecan and their use as antihistamines |
| FR2872813B1 (fr) | 2004-07-09 | 2007-01-19 | Sanofi Synthelabo | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| GB0421908D0 (en) * | 2004-10-01 | 2004-11-03 | Angeletti P Ist Richerche Bio | New uses |
| FR2876692B1 (fr) * | 2004-10-19 | 2007-02-23 | Sanofi Aventis Sa | Derives de 2-amido-4-phenylthiazole, leur preparation et leur application en therapeutique |
| EP1833807A1 (en) * | 2005-01-05 | 2007-09-19 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| CN101137657B (zh) | 2005-03-08 | 2011-02-02 | 詹森药业有限公司 | 作为神经激肽（nk1）拮抗剂的二氮杂-螺-[4.4]-壬烷衍生物 |
| BRPI0608910A2 (pt) * | 2005-05-09 | 2010-02-17 | Achillion Pharmaceuticals Inc | uso de um composto da fórmula ou um sal ou hidrato farmaceuticamente aceitável desse, composto ou sal ou hidrato do mesmo, composição farmacêutica e composição farmacêutica embalada |
| WO2007053495A2 (en) * | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
| US8067415B2 (en) | 2005-11-01 | 2011-11-29 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of CCR2 |
| WO2007053498A1 (en) * | 2005-11-01 | 2007-05-10 | Millennium Pharmaceuticals, Inc. | Compounds useful as antagonists of ccr2 |
| FR2895989B1 (fr) | 2006-01-06 | 2010-04-30 | Sanofi Aventis | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| EP2059515A2 (en) * | 2006-04-12 | 2009-05-20 | Pfizer Limited | Pyrrolidine derivatives as modulators of chemokine ccr5 receptors |
| RU2303597C1 (ru) * | 2006-05-12 | 2007-07-27 | Иващенко Андрей Александрович | Фармацевтическая композиция, способы ее получения и применения |
| CN101096363B (zh) | 2006-06-27 | 2011-05-11 | 中国人民解放军军事医学科学院毒物药物研究所 | 2,4,5-三取代噻唑类化合物、其制备方法、药物组合物及其制药用途 |
| US20080076120A1 (en) * | 2006-09-14 | 2008-03-27 | Millennium Pharmaceuticals, Inc. | Methods for the identification, evaluation and treatment of patients having CC-Chemokine receptor 2 (CCR-2) mediated disorders |
| WO2008060621A2 (en) | 2006-11-17 | 2008-05-22 | Abbott Laboratories | Aminopyrrolidines as chemokine receptor antagonists |
| SI2118099T1 (sl) * | 2007-02-13 | 2011-11-30 | Ab Science | Postopek za sintezo 2-aminotiazolnih spojin kot kinaznih inhibitorjev |
| WO2008124000A2 (en) * | 2007-04-02 | 2008-10-16 | Ligand Pharmaceuticals Incorporated | Thiazole derivatives as androgen receptor modulator compounds |
| CA2687931C (en) | 2007-05-31 | 2016-05-24 | Boehringer Ingelheim International Gmbh | Ccr2 receptor antagonists and uses thereof |
| JP5164181B2 (ja) * | 2007-07-31 | 2013-03-13 | 塩野義製薬株式会社 | トロンボポエチン受容体アゴニスト作用を有する光学活性な化合物を含有する医薬組成物およびその中間体 |
| CN103724328B (zh) | 2008-12-19 | 2015-10-14 | 贝林格尔.英格海姆国际有限公司 | 作为ccr2受体拮抗剂用于治疗炎症、哮喘和copd的环状嘧啶-4-甲酰胺 |
| PL2513093T3 (pl) | 2009-12-17 | 2015-03-31 | Centrexion Therapeutics Corp | Nowi antagoniści receptora CCR2 i ich zastosowanie |
| JP2013526507A (ja) | 2010-05-12 | 2013-06-24 | ベーリンガー インゲルハイム インターナショナル 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ｃｃｒ２受容体アンタゴニスト、その製造方法及び薬物としてのその使用 |
| EP2569295B1 (en) | 2010-05-12 | 2014-11-19 | Boehringer Ingelheim International GmbH | New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments |
| US8841313B2 (en) | 2010-05-17 | 2014-09-23 | Boehringer Ingelheim International Gmbh | CCR2 antagonists and uses thereof |
| JP5636094B2 (ja) | 2010-05-25 | 2014-12-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ２受容体アンタゴニスト |
| EP2576538B1 (en) | 2010-06-01 | 2015-10-28 | Boehringer Ingelheim International GmbH | New CCR2 antagonists |
| WO2013010839A1 (en) | 2011-07-15 | 2013-01-24 | Boehringer Ingelheim International Gmbh | Novel and selective ccr2 antagonists |
| CN103086859B (zh) * | 2011-11-08 | 2015-11-11 | 清华大学 | 2,4-二羟基-5,6-取代-1-卤代苯衍生物、其合成方法及其应用 |
| AU2016287584B2 (en) | 2015-07-02 | 2020-03-26 | Centrexion Therapeutics Corporation | (4-((3R,4R)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2R,6S)-6-(p-tolyl)tetrahydro-2H-pyran-2-yl)methylamino)pyrimidin-4yl)methanone citrate |
| US11028061B2 (en) * | 2015-07-27 | 2021-06-08 | Sanford Burnham Prebys Medical Discovery Institute | Modulators of myocyte lipid accumulation and insulin resistance and methods of use thereof |
| WO2019222393A1 (en) | 2018-05-15 | 2019-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Neuroprotective compositions and methods of using the same |
| WO2020086625A1 (en) * | 2018-10-22 | 2020-04-30 | The Regents Of The University Of California | Vaccine adjuvant |
| CN112004798A (zh) * | 2019-01-07 | 2020-11-27 | 江苏凯迪恩医药科技有限公司 | 一种苯甲酰胺类化合物、中间体、制备方法及应用 |
| US12479816B2 (en) | 2019-02-08 | 2025-11-25 | University of Pittsburgh—of the Commonwealth System of Higher Education | 20-HETE formation inhibitors |
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| DE55034C (de) * | H. KRÜGER in Berlin N., Artilleriestrafse 23 | Zapfenverschlufs für chirurgische Instrumente | ||
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| FR2296497A1 (fr) * | 1974-12-31 | 1976-07-30 | Asselin Robert | Perfectionnement apporte aux fixations de verres optiques sur supports en vue de leur usinage |
| DE2706269C3 (de) * | 1977-02-15 | 1979-08-02 | Th. Goldschmidt Ag, 4300 Essen | Verwendung von Aminderivaten zur Beeinflussung der Theologischen Eigenschaften von Bitumen und bituminösen Massen |
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| GB0108876D0 (en) * | 2001-04-09 | 2001-05-30 | Novartis Ag | Organic Compounds |
| US20030055263A1 (en) * | 2001-07-11 | 2003-03-20 | Boehringer Ingelheim Pharma Kg | Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production |
| WO2003015778A1 (en) | 2001-08-17 | 2003-02-27 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TW200403058A (en) | 2002-04-19 | 2004-03-01 | Bristol Myers Squibb Co | Heterocyclo inhibitors of potassium channel function |
| JP2004256429A (ja) * | 2003-02-26 | 2004-09-16 | Sankyo Co Ltd | イソキノリン誘導体 |
| FR2872813B1 (fr) | 2004-07-09 | 2007-01-19 | Sanofi Synthelabo | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| FR2876692B1 (fr) | 2004-10-19 | 2007-02-23 | Sanofi Aventis Sa | Derives de 2-amido-4-phenylthiazole, leur preparation et leur application en therapeutique |
| FR2895989B1 (fr) | 2006-01-06 | 2010-04-30 | Sanofi Aventis | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
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2003
- 2003-04-25 FR FR0305213A patent/FR2854158B1/fr not_active Expired - Fee Related
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2004
- 2004-04-22 OA OA1200500305A patent/OA13049A/fr unknown
- 2004-04-22 RS YUP-2005/0769A patent/RS20050769A/sr unknown
- 2004-04-22 EP EP04742558A patent/EP1656373B1/fr not_active Expired - Lifetime
- 2004-04-22 AU AU2004234101A patent/AU2004234101A1/en not_active Abandoned
- 2004-04-22 CN CNA2004800180511A patent/CN1826339A/zh active Pending
- 2004-04-22 MX MXPA05011522A patent/MXPA05011522A/es unknown
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- 2004-04-22 AT AT04742558T patent/ATE541843T1/de active
- 2004-04-23 AR ARP040101382A patent/AR044070A1/es unknown
- 2004-04-26 TW TW093111632A patent/TW200510325A/zh unknown
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP0001727A2 (fr) * | 1977-10-19 | 1979-05-02 | Pierre Fabre S.A. | Nouveaux dérivés du phényl-4-(trichloro-2',2',2'-éthoxycarboxamido)-2-thiazole utiles comme médicaments, compositions pharmaceutiques les contenant et leur procédé de préparation |
| EP0638553A1 (de) * | 1993-08-05 | 1995-02-15 | Dr. Karl Thomae GmbH | Carbonsäureamide mit terminaler Carboxylgruppe als Aggregationshemmende Arzneimittel |
| RU2001105984A (ru) * | 1998-08-04 | 2003-01-27 | Астразенека Аб | Производные амидов, которые могут использоваться в качестве ингибиторов цитокинов |
| WO2002018335A1 (en) * | 2000-08-28 | 2002-03-07 | Yamanouchi Pharmaceutical Co., Ltd. | Cyclic amine derivatives |
| WO2002051397A1 (en) * | 2000-12-22 | 2002-07-04 | Ishihara Sangyo Kaisha, Ltd. | Aniline derivatives or salts thereof and cytokine production inhibitors containing the same |
Non-Patent Citations (1)
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| Lombardino et al. "Potent Antiinflammatory N-Heterocyclic 3-Carboxamides of 4-Hydroxy-2-metyl-2H-1,2-Dioxide" JOURNAL OF MEDICINAL CHEMISTRY, 1973, Vol.16, №5, 493-496. * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2576036C2 (ru) * | 2010-03-17 | 2016-02-27 | Тайвекс Терапьютикс Корпорейшн | Модуляторы активности нес1 и способы для них |
| US9409902B2 (en) | 2010-03-17 | 2016-08-09 | Taivex Therapeutics Corporation | Modulators of HEC1 activity and methods therefor |
| US11071736B2 (en) | 2011-11-21 | 2021-07-27 | Taivex Therapeutics Corporation | Modulators of HEC1 activity and methods therefor |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1656373A2 (fr) | 2006-05-17 |
| ECSP056111A (es) | 2006-03-01 |
| WO2004096798A3 (fr) | 2006-01-26 |
| OA13049A (fr) | 2006-11-10 |
| TW200510325A (en) | 2005-03-16 |
| US7777041B2 (en) | 2010-08-17 |
| JP2011126891A (ja) | 2011-06-30 |
| US20090156574A1 (en) | 2009-06-18 |
| CA2521158A1 (fr) | 2004-11-11 |
| CN1826339A (zh) | 2006-08-30 |
| KR20060006935A (ko) | 2006-01-20 |
| FR2854158A1 (fr) | 2004-10-29 |
| US20060135575A1 (en) | 2006-06-22 |
| FR2854158B1 (fr) | 2006-11-17 |
| WO2004096798A2 (fr) | 2004-11-11 |
| ATE541843T1 (de) | 2012-02-15 |
| RS20050769A (sr) | 2007-11-15 |
| NO20054905D0 (no) | 2005-10-24 |
| CR8037A (es) | 2008-07-29 |
| AR044070A1 (es) | 2005-08-24 |
| CO5640106A2 (es) | 2006-05-31 |
| US7504511B2 (en) | 2009-03-17 |
| ZA200508608B (en) | 2007-01-31 |
| JP4839208B2 (ja) | 2011-12-21 |
| JP2006524669A (ja) | 2006-11-02 |
| EP1656373B1 (fr) | 2012-01-18 |
| TNSN05254A1 (en) | 2007-07-10 |
| MA27769A1 (fr) | 2006-02-01 |
| AU2004234101A1 (en) | 2004-11-11 |
| MXPA05011522A (es) | 2006-01-23 |
| RU2005136663A (ru) | 2006-03-20 |
| BRPI0409716A (pt) | 2006-05-02 |
| NO20054905L (no) | 2006-01-25 |
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| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20090423 |