PH12015502745B1 - 4-alkynyl imidazole derivative and medicine comprising same as active ingredient - Google Patents
4-alkynyl imidazole derivative and medicine comprising same as active ingredient Download PDFInfo
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- PH12015502745B1 PH12015502745B1 PH12015502745A PH12015502745A PH12015502745B1 PH 12015502745 B1 PH12015502745 B1 PH 12015502745B1 PH 12015502745 A PH12015502745 A PH 12015502745A PH 12015502745 A PH12015502745 A PH 12015502745A PH 12015502745 B1 PH12015502745 B1 PH 12015502745B1
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- 239000003814 drug Substances 0.000 title abstract description 27
- 239000004480 active ingredient Substances 0.000 title description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 150000001875 compounds Chemical class 0.000 claims description 220
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 101150109738 Ptger4 gene Proteins 0.000 abstract description 38
- 201000010099 disease Diseases 0.000 abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 36
- 208000002193 Pain Diseases 0.000 abstract description 29
- 230000036407 pain Effects 0.000 abstract description 29
- 206010061218 Inflammation Diseases 0.000 abstract description 18
- 230000003042 antagnostic effect Effects 0.000 abstract description 17
- 208000026278 immune system disease Diseases 0.000 abstract description 14
- 230000004054 inflammatory process Effects 0.000 abstract description 14
- 208000027866 inflammatory disease Diseases 0.000 abstract description 7
- 230000004913 activation Effects 0.000 abstract description 6
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 230000006378 damage Effects 0.000 abstract description 5
- 230000000763 evoking effect Effects 0.000 abstract description 4
- 229940035676 analgesics Drugs 0.000 abstract description 3
- 239000000730 antalgic agent Substances 0.000 abstract description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract description 3
- 210000000447 Th1 cell Anatomy 0.000 abstract 1
- 210000000068 Th17 cell Anatomy 0.000 abstract 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 306
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 219
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 109
- 239000000243 solution Substances 0.000 description 106
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 102
- 239000012044 organic layer Substances 0.000 description 97
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
- 239000002904 solvent Substances 0.000 description 93
- 239000000203 mixture Substances 0.000 description 88
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 84
- 239000011541 reaction mixture Substances 0.000 description 81
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 66
- 238000010898 silica gel chromatography Methods 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 59
- 238000000605 extraction Methods 0.000 description 59
- 239000007864 aqueous solution Substances 0.000 description 57
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- -1 hydroxyethyl group Chemical group 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 43
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
- 238000000034 method Methods 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 229920006395 saturated elastomer Polymers 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 32
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 31
- 239000011877 solvent mixture Substances 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 230000009471 action Effects 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- 229960002986 dinoprostone Drugs 0.000 description 20
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 230000001404 mediated effect Effects 0.000 description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000007821 HATU Substances 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 13
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- 230000035484 reaction time Effects 0.000 description 13
- CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 12
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 12
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
- 239000002464 receptor antagonist Substances 0.000 description 11
- 229940044551 receptor antagonist Drugs 0.000 description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
- 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 10
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 10
- PZPSRTWFJCGJLP-UHFFFAOYSA-N hydron;methyl 4-(aminomethyl)cyclohexane-1-carboxylate;chloride Chemical compound Cl.COC(=O)C1CCC(CN)CC1 PZPSRTWFJCGJLP-UHFFFAOYSA-N 0.000 description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- GIZCKBSSWNIUMZ-UHFFFAOYSA-N methyl 4-(aminomethyl)benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(CN)C=C1 GIZCKBSSWNIUMZ-UHFFFAOYSA-N 0.000 description 9
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 201000006417 multiple sclerosis Diseases 0.000 description 8
- 238000006386 neutralization reaction Methods 0.000 description 8
- 230000001376 precipitating effect Effects 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
- 239000005711 Benzoic acid Substances 0.000 description 7
- 235000010233 benzoic acid Nutrition 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 7
- 230000028709 inflammatory response Effects 0.000 description 7
- 150000002825 nitriles Chemical class 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 7
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- BTGXDHVCIKPJTG-MEZFUOHNSA-N Cl.N=1NN=NC1[C@@H]1CC[C@H](CC1)CN Chemical compound Cl.N=1NN=NC1[C@@H]1CC[C@H](CC1)CN BTGXDHVCIKPJTG-MEZFUOHNSA-N 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 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 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- 150000008282 halocarbons Chemical class 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- BADCIGONGJEOFJ-UHFFFAOYSA-N methyl 2-chloro-3-[[4-(trifluoromethyl)phenyl]methyl]imidazole-4-carboxylate Chemical compound ClC=1N(C(=CN=1)C(=O)OC)CC1=CC=C(C=C1)C(F)(F)F BADCIGONGJEOFJ-UHFFFAOYSA-N 0.000 description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 6
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- 239000007858 starting material Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
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- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229940114079 arachidonic acid Drugs 0.000 description 5
- 235000021342 arachidonic acid Nutrition 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
- 125000004438 haloalkoxy group Chemical group 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- DVLGIQNHKLWSRU-UHFFFAOYSA-N methyl 1h-imidazole-5-carboxylate Chemical compound COC(=O)C1=CN=CN1 DVLGIQNHKLWSRU-UHFFFAOYSA-N 0.000 description 5
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- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 4
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/4164—1,3-Diazoles
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- A61K31/4164—1,3-Diazoles
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- A61K31/4245—Oxadiazoles
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D401/02—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
- C07D401/02—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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D413/12—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 chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
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| JP2013123968 | 2013-06-12 | ||
| PCT/JP2014/065643 WO2014200075A1 (ja) | 2013-06-12 | 2014-06-12 | ４－アルキニルイミダゾール誘導体およびそれを有効成分として含有する医薬 |
Publications (2)
| Publication Number | Publication Date |
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| PH12015502745A1 PH12015502745A1 (en) | 2016-03-14 |
| PH12015502745B1 true PH12015502745B1 (en) | 2019-01-25 |
Family
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| PH12015502745A PH12015502745B1 (en) | 2013-06-12 | 2015-12-09 | 4-alkynyl imidazole derivative and medicine comprising same as active ingredient |
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| HUE039015T2 (hu) * | 2013-06-12 | 2018-12-28 | Kaken Pharma Co Ltd | 4-Alkinil-imidazol-származék és ezt hatóanyagként tartalmazó gyógyszerkészítmény |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| WO2018094140A1 (en) * | 2016-11-18 | 2018-05-24 | Vps-3, Inc. | 4-(6-(2-(2,4-difluorophenyl)-1.1-difluoro-2-hydroxy-3-(5-mercapto-1h-1,2,4-triazol-1-yl) propyl)pyridin-3-yl)oxy)benzonitrile and processes of preparation |
| AU2018268311B2 (en) | 2017-05-18 | 2022-02-10 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives as PGE2 receptor modulators |
| WO2018210992A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives |
| EP3625224B1 (en) | 2017-05-18 | 2021-08-04 | Idorsia Pharmaceuticals Ltd | N-substituted indole derivatives |
| US11325899B2 (en) | 2017-05-18 | 2022-05-10 | Idorsia Pharmaceuticals Ltd | Benzofurane and benzothiophene derivatives as PGE2 receptor modulators |
| WO2018210994A1 (en) | 2017-05-18 | 2018-11-22 | Idorsia Pharmaceuticals Ltd | Phenyl derivatives as pge2 receptor modulators |
| JP7211358B2 (ja) | 2017-05-22 | 2023-01-24 | 小野薬品工業株式会社 | Ｅｐ４アンタゴニスト |
| JP2020142989A (ja) * | 2017-06-21 | 2020-09-10 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | イミダゾール誘導体及びそれを含有する医薬 |
| WO2019149286A1 (en) * | 2018-02-05 | 2019-08-08 | Shenzhen Ionova Life Science Co., Ltd. | Heterobicyclic carboxylic acids for treating cancer or inflammatory diseases |
| CN108997252B (zh) * | 2018-07-27 | 2020-04-28 | 常州大学 | 一种恶二唑衍生物的绿色合成方法 |
| WO2022102731A1 (ja) | 2020-11-13 | 2022-05-19 | 小野薬品工業株式会社 | Ｅｐ４拮抗薬と免疫チェックポイント阻害物質との併用によるがん治療 |
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| CA2436551A1 (en) | 2001-01-31 | 2002-08-08 | Pfizer Products Inc. | Thiazolyl-, oxazolyl-, pyrrolyl-, and imidazolyl-acid amide derivatives useful as inhibitors of pde4 isozymes |
| PL368129A1 (en) * | 2001-08-09 | 2005-03-21 | Ono Pharmaceutical Co, Ltd. | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
| WO2003099857A1 (en) | 2002-05-23 | 2003-12-04 | Theratechnologies Inc. | Antagonistic peptides of prostaglandin e2 receptor subtype ep4 |
| CA2536870C (en) | 2003-09-03 | 2009-10-27 | Pfizer Inc. | Phenyl or pyridyl amide compounds as prostaglandin e2 antagonists |
| EP1756043B1 (en) | 2004-05-04 | 2009-07-01 | RaQualia Pharma Inc | Ortho substituted aryl or heteroaryl amide compounds |
| CN1950333A (zh) | 2004-05-04 | 2007-04-18 | 辉瑞大药厂 | 取代的甲基芳基或杂芳基酰胺化合物 |
| RU2410377C2 (ru) * | 2005-02-16 | 2011-01-27 | Солвей Фармасьютикалс Б.В. | Производные 1н-имидазола как модуляторы рецептора каннабиноидов св2 |
| WO2007121578A1 (en) | 2006-04-24 | 2007-11-01 | Merck Frosst Canada Ltd. | Indole amide derivatives as ep4 receptor antagonists |
| AU2007260529B2 (en) | 2006-06-12 | 2012-04-19 | Merck Canada Inc. | Indoline amide derivatives as EP4 receptor ligands |
| ES2421453T3 (es) | 2006-08-11 | 2013-09-02 | Merck Frosst Canada Ltd | Derivados de tiofenocarboxamida como ligandos del receptor EP4 |
| AU2008221194B2 (en) * | 2007-02-26 | 2013-06-27 | Merck Canada Inc. | Indole and indoline cyclopropyl amide derivatives as EP4 receptor antagonists |
| CN101687844B (zh) * | 2007-07-02 | 2013-11-13 | 弗·哈夫曼-拉罗切有限公司 | 用作ccr2受体拮抗剂的咪唑衍生物 |
| EP2460787A1 (en) | 2007-07-03 | 2012-06-06 | Astellas Pharma Inc. | Amide compounds and their use as PGE2 antagonists. |
| RU2479576C9 (ru) | 2008-05-14 | 2014-03-10 | Астеллас Фарма Инк. | Амидное соединение |
| EP2320906B1 (en) | 2008-08-14 | 2016-02-24 | Beta Pharma Canada Inc. | Heterocyclic amide derivatives as ep4 receptor antagonists |
| SMT201700008T1 (it) * | 2010-09-21 | 2017-03-08 | Eisai R&D Man Co Ltd | Composizione farmaceutica |
| ES2545110T3 (es) | 2010-12-10 | 2015-09-08 | Rottapharm Biotech S.R.L. | Derivados de piridinamida como antagonistas del receptor EP4 |
| WO2012103071A2 (en) | 2011-01-25 | 2012-08-02 | Eisai R&D Management Co., Ltd. | Compounds and compositions |
| DK2729445T3 (en) | 2011-07-04 | 2016-01-18 | Rottapharm Biotech Srl | CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS |
| HUE039015T2 (hu) * | 2013-06-12 | 2018-12-28 | Kaken Pharma Co Ltd | 4-Alkinil-imidazol-származék és ezt hatóanyagként tartalmazó gyógyszerkészítmény |
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