CA2109931A1 - Novel imidazole derivative, pharmaceutical use thereof, and intermediate therefor - Google Patents
Novel imidazole derivative, pharmaceutical use thereof, and intermediate thereforInfo
- Publication number
- CA2109931A1 CA2109931A1 CA 2109931 CA2109931A CA2109931A1 CA 2109931 A1 CA2109931 A1 CA 2109931A1 CA 2109931 CA2109931 CA 2109931 CA 2109931 A CA2109931 A CA 2109931A CA 2109931 A1 CA2109931 A1 CA 2109931A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- indole
- imidazol
- ylmethyl
- 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
Links
- 150000002460 imidazoles Chemical class 0.000 title claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 114
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- 229960001340 histamine Drugs 0.000 claims abstract description 16
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 claims abstract description 14
- 238000011321 prophylaxis Methods 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 43
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 229910052727 yttrium Inorganic materials 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 2
- YPNXDOAKDIAFRT-UHFFFAOYSA-N 1-[3-(4-benzhydrylpiperazin-1-yl)butyl]-3-(imidazol-1-ylmethyl)indole-6-carboxylic acid Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(C)CCN(C1=CC(=CC=C11)C(O)=O)C=C1CN1C=CN=C1 YPNXDOAKDIAFRT-UHFFFAOYSA-N 0.000 claims 1
- ASSOGAMHSSRJHN-UHFFFAOYSA-N 1-[3-(4-benzhydrylpiperazin-1-yl)propyl]-3-(imidazol-1-ylmethyl)indole-5-carboxylic acid Chemical compound C1=C(CN2C=NC=C2)C2=CC(C(=O)O)=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 ASSOGAMHSSRJHN-UHFFFAOYSA-N 0.000 claims 1
- HOZQCFWNPXAYPQ-UHFFFAOYSA-N 1-[3-(4-benzhydrylpiperazin-1-yl)propyl]-3-(imidazol-1-ylmethyl)indole-6-carboxylic acid Chemical compound C=1N(CCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C2=CC(C(=O)O)=CC=C2C=1CN1C=CN=C1 HOZQCFWNPXAYPQ-UHFFFAOYSA-N 0.000 claims 1
- GMTLPJYNJIEPQR-UHFFFAOYSA-N 1-[3-(4-benzhydrylpiperazin-1-yl)propyl]-5-(imidazol-1-ylmethyl)-2,3-dihydroindole Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1CCCN(C1=CC=2)CCC1=CC=2CN1C=CN=C1 GMTLPJYNJIEPQR-UHFFFAOYSA-N 0.000 claims 1
- KMAFJJKNZKXDGQ-UHFFFAOYSA-N 1-[3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]propyl]-3-(imidazol-1-ylmethyl)indole-6-carboxylic acid Chemical compound C=1N(CCCN2CCN(CCOC(C=3C=CC=CC=3)C=3C=CC=CC=3)CC2)C2=CC(C(=O)O)=CC=C2C=1CN1C=CN=C1 KMAFJJKNZKXDGQ-UHFFFAOYSA-N 0.000 claims 1
- NFWZHWXBCHTDKN-UHFFFAOYSA-N 1-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propyl]-3-(imidazol-1-ylmethyl)indole-6-carboxylic acid Chemical compound C=1N(CCCN2CCN(CC=3C=CC(Cl)=CC=3)CC2)C2=CC(C(=O)O)=CC=C2C=1CN1C=CN=C1 NFWZHWXBCHTDKN-UHFFFAOYSA-N 0.000 claims 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 50
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 239000002904 solvent Substances 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- -1 methoxy, ethoxy Chemical group 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 230000008602 contraction Effects 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 230000002411 adverse Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 235000006408 oxalic acid Nutrition 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- HYCNLJLHPCMUDU-UHFFFAOYSA-N 1-[3-(4-benzhydrylpiperazin-1-yl)propyl]-5-(imidazol-1-ylmethyl)indole-2-carboxylic acid;trihydrochloride Chemical compound Cl.Cl.Cl.C=1C=C2N(CCCN3CCN(CC3)C(C=3C=CC=CC=3)C=3C=CC=CC=3)C(C(=O)O)=CC2=CC=1CN1C=CN=C1 HYCNLJLHPCMUDU-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 210000001772 blood platelet Anatomy 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 150000002170 ethers Chemical class 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 208000006673 asthma Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 230000001387 anti-histamine Effects 0.000 description 5
- 230000002490 cerebral effect Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 5
- HJBOSDJYJDKRCQ-UHFFFAOYSA-N 5-imidazol-1-yl-2,3-dihydro-1h-indole Chemical compound C=1C=C2NCCC2=CC=1N1C=CN=C1 HJBOSDJYJDKRCQ-UHFFFAOYSA-N 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 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 4
- 239000011575 calcium Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 150000002617 leukotrienes Chemical class 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000002345 respiratory system Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 230000000304 vasodilatating effect Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- DJIRHOOEGKDNFW-UHFFFAOYSA-N 1-[5-(chloromethyl)-2,3-dihydroindol-1-yl]ethanone Chemical compound ClCC1=CC=C2N(C(=O)C)CCC2=C1 DJIRHOOEGKDNFW-UHFFFAOYSA-N 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
- ULZSYRVGEIWSSQ-UHFFFAOYSA-N 5-imidazol-1-yl-1h-indole Chemical compound C1=NC=CN1C1=CC=C(NC=C2)C2=C1 ULZSYRVGEIWSSQ-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 3
- 239000000920 calcium hydroxide Substances 0.000 description 3
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- RNTCWULFNYNFGI-UHFFFAOYSA-N 1-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CCC2=C1 RNTCWULFNYNFGI-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000978776 Senegalia senegal Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000011698 potassium fluoride Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 229960000351 terfenadine Drugs 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 125000005023 xylyl group Chemical group 0.000 description 2
- ZWZHUJPFXQDTHE-UHFFFAOYSA-N 1-(1h-imidazol-2-yl)-2,3-dihydroindole Chemical compound C1CC2=CC=CC=C2N1C1=NC=CN1 ZWZHUJPFXQDTHE-UHFFFAOYSA-N 0.000 description 1
- MBFDHHKTIBKZNR-UHFFFAOYSA-N 1-(2-benzhydryloxyethyl)piperazine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)OCCN1CCNCC1 MBFDHHKTIBKZNR-UHFFFAOYSA-N 0.000 description 1
- WQKQAIXOTCPWFE-UHFFFAOYSA-N 1-(5-bromo-2,3-dihydroindol-1-yl)ethanone Chemical compound BrC1=CC=C2N(C(=O)C)CCC2=C1 WQKQAIXOTCPWFE-UHFFFAOYSA-N 0.000 description 1
- YDCBVTMTQOZMMV-UHFFFAOYSA-N 1-(5-imidazol-1-yl-2,3-dihydroindol-1-yl)ethanone Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1N1C=CN=C1 YDCBVTMTQOZMMV-UHFFFAOYSA-N 0.000 description 1
- ZRFLKBNBFYCKBD-UHFFFAOYSA-N 1-[5-(1h-imidazol-2-ylmethyl)-2,3-dihydroindol-1-yl]ethanone Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1CC1=NC=CN1 ZRFLKBNBFYCKBD-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FRADTKAUXQUOIJ-UHFFFAOYSA-N 3-(imidazol-1-ylmethyl)-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CN1C=CN=C1 FRADTKAUXQUOIJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BBDCCXMBOJDLMO-UHFFFAOYSA-N 4-benzyl-1-(2-chloroethyl)piperidine Chemical compound C1CN(CCCl)CCC1CC1=CC=CC=C1 BBDCCXMBOJDLMO-UHFFFAOYSA-N 0.000 description 1
- OUDSBEJDEXUDEZ-UHFFFAOYSA-N 5-(1h-imidazol-2-yl)-2,3-dihydro-1h-indole Chemical compound C=1C=C2NCCC2=CC=1C1=NC=CN1 OUDSBEJDEXUDEZ-UHFFFAOYSA-N 0.000 description 1
- APRXPLKTRABHFY-UHFFFAOYSA-N 5-(imidazol-1-ylmethyl)-2,3-dihydro-1h-indole Chemical compound C=1C=C2NCCC2=CC=1CN1C=CN=C1 APRXPLKTRABHFY-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PUVBIWIGZNFJEV-UHFFFAOYSA-N C(C)(=O)OOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1.C(C(=O)O)(=O)O.C(C1=CC=CC=C1)(C1=CC=CC=C1)N1CCN(CC1)CCOCC(=O)N1CCC2=CC(=CC=C12)N1C=NC=C1 Chemical compound C(C)(=O)OOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1.C(C(=O)O)(=O)O.C(C1=CC=CC=C1)(C1=CC=CC=C1)N1CCN(CC1)CCOCC(=O)N1CCC2=CC(=CC=C12)N1C=NC=C1 PUVBIWIGZNFJEV-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 206010059109 Cerebral vasoconstriction Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- IEBAHQMNAJHTHV-UHFFFAOYSA-N N1(C=NC=C1)C=1C=C2CCNC2=CC1.C(C(=O)O)(=O)O Chemical compound N1(C=NC=C1)C=1C=C2CCNC2=CC1.C(C(=O)O)(=O)O IEBAHQMNAJHTHV-UHFFFAOYSA-N 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000002590 anti-leukotriene effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZTYLSTGOVIRHMB-UHFFFAOYSA-N ethyl 1-[3-(4-benzhydrylpiperazin-1-yl)propyl]-5-(imidazol-1-ylmethyl)indole-2-carboxylate Chemical compound C=1C=C2N(CCCN3CCN(CC3)C(C=3C=CC=CC=3)C=3C=CC=CC=3)C(C(=O)OCC)=CC2=CC=1CN1C=CN=C1 ZTYLSTGOVIRHMB-UHFFFAOYSA-N 0.000 description 1
- DYELTXAGLHHPNP-UHFFFAOYSA-N ethyl 3-(imidazol-1-ylmethyl)-1h-indole-6-carboxylate Chemical compound C=1NC2=CC(C(=O)OCC)=CC=C2C=1CN1C=CN=C1 DYELTXAGLHHPNP-UHFFFAOYSA-N 0.000 description 1
- JCXFDTAADZRQDV-UHFFFAOYSA-N ethyl 5-(imidazol-1-ylmethyl)-1h-indole-2-carboxylate Chemical compound C=1C=C2NC(C(=O)OCC)=CC2=CC=1CN1C=CN=C1 JCXFDTAADZRQDV-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XNRNNGPBEPRNAR-JQBLCGNGSA-N thromboxane B2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1OC(O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O XNRNNGPBEPRNAR-JQBLCGNGSA-N 0.000 description 1
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical group C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10207192 | 1992-03-27 | ||
| JP102071/1992 | 1992-03-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2109931A1 true CA2109931A1 (en) | 1993-10-14 |
Family
ID=14317541
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2109931 Abandoned CA2109931A1 (en) | 1992-03-27 | 1993-03-26 | Novel imidazole derivative, pharmaceutical use thereof, and intermediate therefor |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0597112A4 (en, 2012) |
| AU (1) | AU658729B2 (en, 2012) |
| CA (1) | CA2109931A1 (en, 2012) |
| TW (1) | TW218870B (en, 2012) |
| WO (1) | WO1993020065A1 (en, 2012) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3719612B2 (ja) * | 1993-06-14 | 2005-11-24 | 塩野義製薬株式会社 | ヘテロ環を含有する尿素誘導体 |
| JP2901226B2 (ja) | 1994-12-26 | 1999-06-07 | バイエル薬品株式会社 | アレルギー性皮膚炎の処置剤 |
| FR2767827A1 (fr) * | 1997-09-03 | 1999-02-26 | Adir | Nouveaux derives de l'indole et de l'indazole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU779073B2 (en) * | 1998-12-23 | 2005-01-06 | Nps Allelix Corp. | Indole and indolizidine derivatives for the treatment of migraine |
| FR2803298A1 (fr) * | 1999-12-30 | 2001-07-06 | Adir | Nouvelles urees lineaires ou cycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP1283199A4 (en) * | 2000-05-16 | 2003-12-17 | Takeda Chemical Industries Ltd | MELANINE CONCENTRATING HORMONE ANTAGONISTS |
| ES2246742B1 (es) * | 2005-09-06 | 2007-02-01 | Prous Institute For Biomedical Research S.A. | Uso de un derivado de imidazol. |
| US8399666B2 (en) | 2005-11-04 | 2013-03-19 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| US7977359B2 (en) | 2005-11-04 | 2011-07-12 | Amira Pharmaceuticals, Inc. | 5-lipdxygenase-activating protein (FLAP) inhibitors |
| GB2431927B (en) | 2005-11-04 | 2010-03-17 | Amira Pharmaceuticals Inc | 5-Lipoxygenase-activating protein (FLAP) inhibitors |
| TW200920369A (en) | 2007-10-26 | 2009-05-16 | Amira Pharmaceuticals Inc | 5-lipoxygenase activating protein (flap) inhibitor |
| EP2285803A4 (en) | 2008-05-23 | 2011-10-05 | Amira Pharmaceuticals Inc | Inhibitor of 5-Lipoxygenase Activating Protein |
| US8546431B2 (en) | 2008-10-01 | 2013-10-01 | Panmira Pharmaceuticals, Llc | 5-lipoxygenase-activating protein (FLAP) inhibitors |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| EP2970177A1 (en) | 2013-03-15 | 2016-01-20 | Pfizer Inc. | Indole compounds that activate ampk |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0003901B1 (en) * | 1978-02-24 | 1981-08-05 | Pfizer Limited | 3-(imidazol-1-ylalkyl)indoles as selective inhibitors of thromboxane synthetase,pharmaceutical compositions thereof, and methods for preparing them |
| DK151884C (da) * | 1979-03-07 | 1988-06-13 | Pfizer | Analogifremgangsmaade til fremstilling af 3-(1-imidazolylalkyl)indolderivater eller farmaceutisk acceptable syreadditionssalte deraf |
| ZA806531B (en) * | 1979-11-02 | 1981-06-24 | Hoffmann La Roche | Antiobesity and insulin lowering agents |
| NL8005946A (nl) * | 1979-11-02 | 1981-06-01 | Hoffmann La Roche | Middelen tegen vetzucht en verhoogde vetspiegel. |
| GR75101B (en, 2012) * | 1980-10-23 | 1984-07-13 | Pfizer | |
| KR840000529A (ko) * | 1981-07-07 | 1984-02-25 | 콘스탄틴 루이스 클레멘트 | 인돌 유도체의 제조방법 |
| ZA825413B (en) * | 1981-08-26 | 1983-06-29 | Pfizer | Thromboxane synthetase inhibitors, processes for their production, and pharmaceutical compositions comprising them |
| JPH037281A (ja) * | 1989-03-31 | 1991-01-14 | Kyoto Yakuhin Kogyo Kk | 新規イミダゾール誘導体およびその医薬用途 |
| PT95899A (pt) * | 1989-11-17 | 1991-09-13 | Glaxo Group Ltd | Processo para a preparacao de derivados indole |
| PH31175A (en) * | 1990-10-31 | 1998-03-20 | Squibb & Sons Inc | Indole and benzimi-dazole-substituted imidazole and benzimidazole derivatives. |
-
1993
- 1993-03-26 CA CA 2109931 patent/CA2109931A1/en not_active Abandoned
- 1993-03-26 EP EP19930906837 patent/EP0597112A4/en not_active Withdrawn
- 1993-03-26 AU AU37680/93A patent/AU658729B2/en not_active Ceased
- 1993-03-26 WO PCT/JP1993/000378 patent/WO1993020065A1/ja not_active Application Discontinuation
- 1993-04-24 TW TW82103172A patent/TW218870B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| AU658729B2 (en) | 1995-04-27 |
| WO1993020065A1 (en) | 1993-10-14 |
| TW218870B (en, 2012) | 1994-01-11 |
| EP0597112A4 (en) | 1994-06-22 |
| EP0597112A1 (en) | 1994-05-18 |
| AU3768093A (en) | 1993-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5767283A (en) | 7-Amino-1H-indoles | |
| CA2109931A1 (en) | Novel imidazole derivative, pharmaceutical use thereof, and intermediate therefor | |
| US4816454A (en) | 4,5-dihydro-3(2H)-pyridazinones and their pharmacological use | |
| IE913473A1 (en) | Quinazoline derivatives and their preparation | |
| KR910006863B1 (ko) | 인돌-3-카르복사미드 유도체의 제조방법 | |
| KR900006990B1 (ko) | 카르바모일피롤리돈 유도체 및 노인성 치매용 약제 | |
| IL177422A (en) | Derivatives of alkylpiperazine- and alkylhomopiperazine-carboxylates, preparation method thereof and use of same as faah enzyme inhibitors | |
| WO2002049632A1 (fr) | Inhibiteurs de production et de liberation de cytokines inflammatoires | |
| WO1995032960A1 (fr) | Derive de benzimidazol | |
| JPH04145079A (ja) | インドール誘導体およびその用途 | |
| NZ223194A (en) | 1,2-dihydro-3h-indazol-3-one derivatives and 5-lipoxygenase-inhibiting compositions | |
| PL167101B1 (pl) | Sposób wytwarzania pochodnych tiazolu PL PL PL PL PL PL | |
| JPH04257570A (ja) | ピペラジン誘導体 | |
| SE465928B (sv) | 1,2,4-triazolonfoereningar med antidepressiv aktivitet, foerfarande foer framstaellning av dessa och en farmaceutisk komposition | |
| BG66240B1 (bg) | Аминоалкилбензоил - бензофурани или бензотиофени, метод за получаването им и състави, които ги съдържат | |
| US4404384A (en) | O-[3-(4-Substituted-piperazin-1-yl)-2-hydroxypropyl]-hydroxylamines | |
| WO1993022290A1 (en) | Novel substituted tertiary amino compound or salt thereof | |
| US4565817A (en) | Theophyllinyl-alkyl-oxadiazoles, process for the preparation thereof and pharmaceutical compositions containing same | |
| US5330986A (en) | Indole-7-carboxamide derivatives | |
| CA1317948C (en) | Omega-¬(hetero)alkyl|benz¬cd|-indol-2-amines | |
| FI76076C (fi) | Foerfarande foer framstaellning av farmakologiskt vaerdefulla heterocykliska foereningar. | |
| US4001280A (en) | Chromone derivatives | |
| JPH02178263A (ja) | アザアズレン誘導体、その製造法およびそれを有効成分とする抗アレルギー剤および抗炎症剤 | |
| JP2000501070A (ja) | ５−ＨＴ▲下１Ｄα▼アゴニストとしての置換インドリルプロピルピペラジン誘導体 | |
| AP745A (en) | Heterocyclic compounds and their use in treatment of CNS disorders. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |