CN103159692B - 四唑取代的芳基酰胺类 - Google Patents
四唑取代的芳基酰胺类 Download PDFInfo
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- CN103159692B CN103159692B CN201310005567.3A CN201310005567A CN103159692B CN 103159692 B CN103159692 B CN 103159692B CN 201310005567 A CN201310005567 A CN 201310005567A CN 103159692 B CN103159692 B CN 103159692B
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- Prior art keywords
- alkyl
- methyl
- ylmethyl
- propyl
- pyridin
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 61
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 45
- 201000010099 disease Diseases 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 27
- -1 5-methyl-pyridin-2-yl Chemical group 0.000 claims description 1049
- 125000000217 alkyl group Chemical group 0.000 claims description 572
- 229910052739 hydrogen Inorganic materials 0.000 claims description 140
- 239000001257 hydrogen Substances 0.000 claims description 140
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 124
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 claims description 43
- 238000002360 preparation method Methods 0.000 claims description 36
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 230000036407 pain Effects 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 19
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 15
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000002496 gastric effect Effects 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 102000000033 Purinergic Receptors Human genes 0.000 claims description 6
- 108010080192 Purinergic Receptors Proteins 0.000 claims description 6
- 208000025609 Urogenital disease Diseases 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 208000027753 pain disease Diseases 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 55
- 125000001544 thienyl group Chemical group 0.000 abstract description 10
- 102100040460 P2X purinoceptor 3 Human genes 0.000 abstract description 8
- 101710189970 P2X purinoceptor 3 Proteins 0.000 abstract description 8
- 125000003831 tetrazolyl group Chemical group 0.000 abstract description 5
- 230000001404 mediated effect Effects 0.000 abstract description 4
- TZHOVNUCGUXMCS-UHFFFAOYSA-N 5-(2-ethynyl-5-propan-2-ylpyridin-4-yl)oxypyrimidine-2,4-diamine Chemical compound C(#C)C1=NC=C(C(=C1)OC=1C(=NC(=NC=1)N)N)C(C)C TZHOVNUCGUXMCS-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- 150000002431 hydrogen Chemical class 0.000 description 72
- 125000003545 alkoxy group Chemical group 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 229910052799 carbon Inorganic materials 0.000 description 55
- 125000001153 fluoro group Chemical group F* 0.000 description 55
- 125000001309 chloro group Chemical group Cl* 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- 239000002904 solvent Substances 0.000 description 52
- 239000000203 mixture Substances 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- 125000001072 heteroaryl group Chemical group 0.000 description 48
- 239000007787 solid Substances 0.000 description 44
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 39
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 39
- 125000000623 heterocyclic group Chemical group 0.000 description 39
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 37
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 35
- 239000002585 base Substances 0.000 description 34
- 208000002193 Pain Diseases 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 29
- 239000011737 fluorine Substances 0.000 description 29
- 229910052731 fluorine Inorganic materials 0.000 description 29
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 28
- 229910052801 chlorine Inorganic materials 0.000 description 28
- 150000003254 radicals Chemical class 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 28
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 125000003118 aryl group Chemical group 0.000 description 24
- 125000004093 cyano group Chemical group *C#N 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000004480 active ingredient Substances 0.000 description 20
- 125000000753 cycloalkyl group Chemical group 0.000 description 20
- 125000005843 halogen group Chemical group 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- 239000007832 Na2SO4 Substances 0.000 description 19
- 125000002947 alkylene group Chemical group 0.000 description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
- 230000008569 process Effects 0.000 description 19
- 125000004429 atom Chemical group 0.000 description 17
- 238000010189 synthetic method Methods 0.000 description 17
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 125000002098 pyridazinyl group Chemical group 0.000 description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 241000700159 Rattus Species 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 125000000335 thiazolyl group Chemical group 0.000 description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 206010020853 Hypertonic bladder Diseases 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 12
- 125000003943 azolyl group Chemical group 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 208000002551 irritable bowel syndrome Diseases 0.000 description 12
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 206010020751 Hypersensitivity Diseases 0.000 description 11
- 208000026935 allergic disease Diseases 0.000 description 11
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 11
- 230000009610 hypersensitivity Effects 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 125000000000 cycloalkoxy group Chemical group 0.000 description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000001335 aliphatic alkanes Chemical class 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 230000008602 contraction Effects 0.000 description 9
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- 102000002294 Purinergic P2X Receptors Human genes 0.000 description 8
- 108010000836 Purinergic P2X Receptors Proteins 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 125000003226 pyrazolyl group Chemical group 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 7
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 7
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 7
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 210000001072 colon Anatomy 0.000 description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
- 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 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- IQQPUQIPEUETMX-UHFFFAOYSA-N methyl 3-amino-5-(4-methylphenyl)benzoate Chemical compound COC(=O)C1=CC(N)=CC(C=2C=CC(C)=CC=2)=C1 IQQPUQIPEUETMX-UHFFFAOYSA-N 0.000 description 7
- YWTUCRBEYQHQGN-UHFFFAOYSA-N methyl 3-amino-5-(5-methylpyridin-2-yl)benzoate Chemical compound COC(=O)C1=CC(N)=CC(C=2N=CC(C)=CC=2)=C1 YWTUCRBEYQHQGN-UHFFFAOYSA-N 0.000 description 7
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 7
- 125000003386 piperidinyl group Chemical group 0.000 description 7
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- MPBCUCGKHDEUDD-UHFFFAOYSA-N (5-methylpyrazin-2-yl)methanamine Chemical compound CC1=CN=C(CN)C=N1 MPBCUCGKHDEUDD-UHFFFAOYSA-N 0.000 description 6
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
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- 125000001188 haloalkyl group Chemical group 0.000 description 6
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- GHZUTMKPZFZYSP-UHFFFAOYSA-N methyl 3-iodo-5-nitrobenzoate Chemical compound COC(=O)C1=CC(I)=CC([N+]([O-])=O)=C1 GHZUTMKPZFZYSP-UHFFFAOYSA-N 0.000 description 6
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- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 5
- VKYJXDOIGACUMA-UHFFFAOYSA-N 3-(4-methylphenyl)-5-(tetrazol-1-yl)benzoic acid Chemical compound C1=CC(C)=CC=C1C1=CC(C(O)=O)=CC(N2N=NN=C2)=C1 VKYJXDOIGACUMA-UHFFFAOYSA-N 0.000 description 5
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
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- 229920000392 Zymosan Polymers 0.000 description 5
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- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
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- 125000002837 carbocyclic group Chemical group 0.000 description 5
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- 125000006351 ethylthiomethyl group Chemical group [H]C([H])([H])C([H])([H])SC([H])([H])* 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 125000002757 morpholinyl group Chemical group 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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| JP5539235B2 (ja) | 2008-02-29 | 2014-07-02 | エボテック・アーゲー | アミド化合物、組成物およびそれらの使用 |
| JP5608655B2 (ja) * | 2008-09-18 | 2014-10-15 | エヴォテック アーゲー | P2x3受容体活性のモジュレーター |
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