JPH0660181B2 - 新規な薬理学的に活性なピラゾロピリジン類 - Google Patents
新規な薬理学的に活性なピラゾロピリジン類Info
- Publication number
- JPH0660181B2 JPH0660181B2 JP58238063A JP23806383A JPH0660181B2 JP H0660181 B2 JPH0660181 B2 JP H0660181B2 JP 58238063 A JP58238063 A JP 58238063A JP 23806383 A JP23806383 A JP 23806383A JP H0660181 B2 JPH0660181 B2 JP H0660181B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- pyridine
- phenyl
- carboxylic acid
- pyrazolo
- 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.)
- Expired - Lifetime
Links
- 150000005229 pyrazolopyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- 238000000034 method Methods 0.000 claims abstract description 22
- -1 nitro, pentafluorophenyl Chemical group 0.000 claims description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000001246 bromo group Chemical group Br* 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 2
- 150000002334 glycols Chemical class 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 3
- PMHIZRNLJGEXDI-UHFFFAOYSA-N 1,6-dimethyl-3-(2-methylpropyl)-4-(2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical compound CC(C)Cc1nn(C)c2NC(C)=C(C(c12)c1ccccc1[N+]([O-])=O)C(O)=O PMHIZRNLJGEXDI-UHFFFAOYSA-N 0.000 claims 1
- 239000002220 antihypertensive agent Substances 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 239000005557 antagonist Substances 0.000 abstract description 4
- 230000000304 vasodilatating effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 238000002844 melting Methods 0.000 description 33
- 230000008018 melting Effects 0.000 description 33
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000011575 calcium Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- ZFDGMMZLXSFNFU-UHFFFAOYSA-N 2,5-dimethylpyrazol-3-amine Chemical compound CC=1C=C(N)N(C)N=1 ZFDGMMZLXSFNFU-UHFFFAOYSA-N 0.000 description 5
- KGEGNOFPNKTJNU-UHFFFAOYSA-N 2-methyl-5-propan-2-ylpyrazol-3-amine Chemical compound CC(C)C=1C=C(N)N(C)N=1 KGEGNOFPNKTJNU-UHFFFAOYSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- KCYRMURRLLYLPU-UHFFFAOYSA-N 1-methyl-3-phenyl-1H-pyrazol-5-amine Chemical compound C1=C(N)N(C)N=C1C1=CC=CC=C1 KCYRMURRLLYLPU-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 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
- 238000007796 conventional method Methods 0.000 description 3
- 235000013681 dietary sucrose Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- MBEYCURLTGQATH-UHFFFAOYSA-N 2-methyl-5-propylpyrazol-3-amine Chemical compound CCCC=1C=C(N)N(C)N=1 MBEYCURLTGQATH-UHFFFAOYSA-N 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- IKVSYFLSDPAAKG-UHFFFAOYSA-N 5-butyl-2-methylpyrazol-3-amine Chemical compound CCCCC=1C=C(N)N(C)N=1 IKVSYFLSDPAAKG-UHFFFAOYSA-N 0.000 description 2
- PWSZRRFDVPMZGM-UHFFFAOYSA-N 5-phenyl-1h-pyrazol-3-amine Chemical compound N1N=C(N)C=C1C1=CC=CC=C1 PWSZRRFDVPMZGM-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000005792 cardiovascular activity Effects 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 210000004534 cecum Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 2
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- OMMAKIZTTOIGFL-UHFFFAOYSA-N methyl 1,3,6-trimethyl-4-(2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C1=C(C)NC(N(N=C2C)C)=C2C1C1=CC=CC=C1[N+]([O-])=O OMMAKIZTTOIGFL-UHFFFAOYSA-N 0.000 description 2
- LYUBYLJQOZIBQB-UHFFFAOYSA-N methyl 2-[(3-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)=CC1=CC=CC([N+]([O-])=O)=C1 LYUBYLJQOZIBQB-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
- SXOFMEWDEKEVJU-UHFFFAOYSA-N 2,5-diphenylpyrazol-3-amine Chemical compound NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 SXOFMEWDEKEVJU-UHFFFAOYSA-N 0.000 description 1
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- 125000005842 heteroatom Chemical group 0.000 description 1
- LWTSGMRYWDGKCL-UHFFFAOYSA-N hexyl 4-(2,3-dimethylphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCCCCCOC(=O)C1=C(C)NC(N(N=C2C)C)=C2C1C1=CC=CC(C)=C1C LWTSGMRYWDGKCL-UHFFFAOYSA-N 0.000 description 1
- YOWFCVPKZNLAFD-UHFFFAOYSA-N hexyl 4-(2,3-dimethylphenyl)-3-ethyl-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound C(CCCCC)OC(=O)C=1C(C2=C(NC=1C)N(N=C2CC)C)C1=C(C(=CC=C1)C)C YOWFCVPKZNLAFD-UHFFFAOYSA-N 0.000 description 1
- UOMMXBNQAZFJNK-UHFFFAOYSA-N hexyl 4-(2,3-dimethylphenyl)-6-methyl-3-phenyl-2,4-dihydro-1h-pyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCCCCCOC(=O)C1=C(C)NC=2NN=C(C=3C=CC=CC=3)C=2C1C1=CC=CC(C)=C1C UOMMXBNQAZFJNK-UHFFFAOYSA-N 0.000 description 1
- MOPUYFJPASIRTR-UHFFFAOYSA-N hexyl 4-(2,6-dimethylphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCCCCCOC(=O)C1=C(C)NC(N(N=C2C)C)=C2C1C1=C(C)C=CC=C1C MOPUYFJPASIRTR-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000011630 iodine Substances 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
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940089027 kcl-40 Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- APKKCRAKPMSAEI-JXMROGBWSA-N methyl (2e)-2-[(2-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(\C(C)=O)=C\C1=CC=CC=C1[N+]([O-])=O APKKCRAKPMSAEI-JXMROGBWSA-N 0.000 description 1
- PJBSUOPCRLXUAP-UHFFFAOYSA-N methyl 1,3,6-trimethyl-4-[2-(trifluoromethyl)phenyl]-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C)C)C1=C(C=CC=C1)C(F)(F)F PJBSUOPCRLXUAP-UHFFFAOYSA-N 0.000 description 1
- LKHUJEVRTIGZSC-UHFFFAOYSA-N methyl 1,3,6-trimethyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C)C)C1=CC(=CC=C1)C(F)(F)F LKHUJEVRTIGZSC-UHFFFAOYSA-N 0.000 description 1
- SLMNFIZIOWGMQS-UHFFFAOYSA-N methyl 1,6-dimethyl-3-propanoyl-4-[3-(trifluoromethyl)phenyl]-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C(CC)=O)C)C1=CC(=CC=C1)C(F)(F)F SLMNFIZIOWGMQS-UHFFFAOYSA-N 0.000 description 1
- DADIZIDETDJZFK-UHFFFAOYSA-N methyl 1,6-dimethyl-4-(2-nitrophenyl)-3-propyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2CCC)C)C1=C(C=CC=C1)[N+](=O)[O-] DADIZIDETDJZFK-UHFFFAOYSA-N 0.000 description 1
- NRAOPSWZCPSJLM-UHFFFAOYSA-N methyl 3-tert-butyl-1,6-dimethyl-4-(2-nitrophenyl)-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C1=C(C)NC(N(N=C2C(C)(C)C)C)=C2C1C1=CC=CC=C1[N+]([O-])=O NRAOPSWZCPSJLM-UHFFFAOYSA-N 0.000 description 1
- DLSBNALPJDUHQM-UHFFFAOYSA-N methyl 4-(2,3-dimethoxyphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C)C)C1=C(C(=CC=C1)OC)OC DLSBNALPJDUHQM-UHFFFAOYSA-N 0.000 description 1
- FQKJQIYAKQQGLR-UHFFFAOYSA-N methyl 4-(2,3-dimethoxyphenyl)-1,6-dimethyl-3-propanoyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C(CC)=O)C)C1=C(C(=CC=C1)OC)OC FQKJQIYAKQQGLR-UHFFFAOYSA-N 0.000 description 1
- AMLLMFICLGFRFD-UHFFFAOYSA-N methyl 4-(2,3-dimethoxyphenyl)-3-ethyl-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound C1=2C(CC)=NN(C)C=2NC(C)=C(C(=O)OC)C1C1=CC=CC(OC)=C1OC AMLLMFICLGFRFD-UHFFFAOYSA-N 0.000 description 1
- PIGQBVMSWUNGMM-UHFFFAOYSA-N methyl 4-(2-methoxycarbonylphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C)C)C1=C(C=CC=C1)C(=O)OC PIGQBVMSWUNGMM-UHFFFAOYSA-N 0.000 description 1
- PSZPUZYNMGXSBB-UHFFFAOYSA-N methyl 4-(2-methoxycarbonylphenyl)-6-methyl-3-phenyl-2,4-dihydro-1h-pyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C1=C(C)NC=2NN=C(C=3C=CC=CC=3)C=2C1C1=CC=CC=C1C(=O)OC PSZPUZYNMGXSBB-UHFFFAOYSA-N 0.000 description 1
- IXBZQQGIGILLSR-UHFFFAOYSA-N methyl 6-methyl-3-phenyl-4-[3-(trifluoromethyl)phenyl]-2,4-dihydro-1h-pyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C1=C(C)NC=2NN=C(C=3C=CC=CC=3)C=2C1C1=CC=CC(C(F)(F)F)=C1 IXBZQQGIGILLSR-UHFFFAOYSA-N 0.000 description 1
- VTWWDOFBSIDSNX-UHFFFAOYSA-N methyl 6-methyl-4-(3-nitrophenyl)-1,3-diphenyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound COC(=O)C=1C(C2=C(NC=1C)N(N=C2C1=CC=CC=C1)C1=CC=CC=C1)C1=CC(=CC=C1)[N+](=O)[O-] VTWWDOFBSIDSNX-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- UMKBLHTZCBNYCJ-UHFFFAOYSA-N n-benzyl-2,5-dimethylpyrazol-3-amine Chemical compound CN1N=C(C)C=C1NCC1=CC=CC=C1 UMKBLHTZCBNYCJ-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- UWULKXAEMKDQSJ-UHFFFAOYSA-N pentyl 3-ethyl-4-(2-ethylphenyl)-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCCCCOC(=O)C1=C(C)NC(N(N=C2CC)C)=C2C1C1=CC=CC=C1CC UWULKXAEMKDQSJ-UHFFFAOYSA-N 0.000 description 1
- ZKFCNZYKDZRRDI-UHFFFAOYSA-N pentyl 4-(2-ethylphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound C(CCCC)OC(=O)C=1C(C2=C(NC=1C)N(N=C2C)C)C1=C(C=CC=C1)CC ZKFCNZYKDZRRDI-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- PQKYUMUBIQWSAR-UHFFFAOYSA-N propan-2-yl 4-(2-ethoxyphenyl)-1,3,6-trimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC1=CC=CC=C1C1C(C(=O)OC(C)C)=C(C)NC2=C1C(C)=NN2C PQKYUMUBIQWSAR-UHFFFAOYSA-N 0.000 description 1
- ILTMRXJPIGJNLG-UHFFFAOYSA-N propan-2-yl 4-(2-ethoxyphenyl)-1,6-dimethyl-3-propanoyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound C(C)(C)OC(=O)C=1C(C2=C(NC=1C)N(N=C2C(CC)=O)C)C1=C(C=CC=C1)OCC ILTMRXJPIGJNLG-UHFFFAOYSA-N 0.000 description 1
- GVCMGNRMXPCCEH-UHFFFAOYSA-N propan-2-yl 4-(2-ethoxyphenyl)-3-ethyl-1,6-dimethyl-4,7-dihydropyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound C(C)(C)OC(=O)C=1C(C2=C(NC=1C)N(N=C2CC)C)C1=C(C=CC=C1)OCC GVCMGNRMXPCCEH-UHFFFAOYSA-N 0.000 description 1
- VXXLCOKHMVLSHX-UHFFFAOYSA-N propan-2-yl 4-(2-ethoxyphenyl)-6-methyl-3-phenyl-2,4-dihydro-1h-pyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC1=CC=CC=C1C1C(C(=O)OC(C)C)=C(C)NC2=C1C(C=1C=CC=CC=1)=NN2 VXXLCOKHMVLSHX-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8236131 | 1982-12-20 | ||
| GB8236131 | 1982-12-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59118786A JPS59118786A (ja) | 1984-07-09 |
| JPH0660181B2 true JPH0660181B2 (ja) | 1994-08-10 |
Family
ID=10535093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58238063A Expired - Lifetime JPH0660181B2 (ja) | 1982-12-20 | 1983-12-19 | 新規な薬理学的に活性なピラゾロピリジン類 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4954508A (en]) |
| EP (1) | EP0114273B1 (en]) |
| JP (1) | JPH0660181B2 (en]) |
| KR (1) | KR890002227B1 (en]) |
| AT (1) | ATE69227T1 (en]) |
| AU (1) | AU574654B2 (en]) |
| DE (1) | DE3382452D1 (en]) |
| DK (1) | DK582083A (en]) |
| ES (2) | ES8601987A1 (en]) |
| FI (1) | FI76337C (en]) |
| GR (1) | GR79111B (en]) |
| IE (1) | IE57305B1 (en]) |
| IL (1) | IL70445A (en]) |
| MY (1) | MY101250A (en]) |
| NO (1) | NO160367C (en]) |
| NZ (1) | NZ206626A (en]) |
| PH (1) | PH20896A (en]) |
| PT (1) | PT77850B (en]) |
| ZA (1) | ZA839092B (en]) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5965089A (ja) * | 1982-10-05 | 1984-04-13 | Shionogi & Co Ltd | ジヒドロピラゾロ〔３，４−ｂ〕ピリジン誘導体およびその製造法 |
| US4873334A (en) * | 1982-10-05 | 1989-10-10 | Shionogi & Co., Ltd. | 4,7-dihydropyrazolo(3,4-b) pyridine derivatives |
| JPS60197685A (ja) * | 1984-03-19 | 1985-10-07 | Shionogi & Co Ltd | ４，７―ジヒドロピラゾロ［３，４―ｂ］ピリジン誘導体とその製造法 |
| JPS6056979A (ja) * | 1983-09-08 | 1985-04-02 | Shionogi & Co Ltd | ４，７−ジヒドロピラゾロ〔３，４−ｂ〕ピリジン誘導体およびその製造法 |
| US4918074A (en) * | 1984-03-12 | 1990-04-17 | Yoshitomi Pharmaceutical Industries, Ltd. | Polyazaheterocycle compounds |
| US4916140A (en) * | 1988-09-28 | 1990-04-10 | Merrell Dow Pharmaceuticals Inc. | Antiepileptic pyrazolopyridines |
| JP2005501800A (ja) * | 2001-02-02 | 2005-01-20 | 三菱ウェルファーマ株式会社 | ジヒドロピラゾロピリジン化合物およびその医薬用途 |
| US6977262B2 (en) | 2001-02-02 | 2005-12-20 | Mitsubishi Pharma Corporation | Dihydropyrazolopyridine compounds and pharmaceutical use thereof |
| WO2005016245A2 (en) * | 2003-06-13 | 2005-02-24 | Zentaris Gmbh | Compounds having inhibitive activity of phosphatidylinositol 3-kinase and methods of use thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773778A (en) * | 1972-01-24 | 1973-11-20 | Squibb & Sons Inc | Sulfur derivatives of pyrazolo (3,4-b)pyridines |
| DE2356684A1 (de) * | 1972-11-15 | 1974-05-16 | Heyden Chem Fab | Neue 4-aminoderivate von pyrazolo (3,4-b)pyridin-5-carboxamiden |
| US4038283A (en) * | 1975-04-30 | 1977-07-26 | E. R. Squibb & Sons, Inc. | 4-Alkoxy or hydroxy derivatives of 2H-pyrazolo[3,4-b]pyridine-5-carboxylic acids and esters |
| GB1568399A (en) * | 1975-10-16 | 1980-05-29 | Squibb & Sons Inc | Pyrazolo pyridine derivatives |
| US4020072A (en) * | 1976-05-04 | 1977-04-26 | E. R. Squibb & Sons, Inc. | 5-Aminomethyl-1H-pyrazolo[3,4-b]pyridines |
| NZ201395A (en) * | 1981-07-30 | 1987-02-20 | Bayer Ag | Pharmaceutical compositions containing 1,4-dihydropyridines and certain of these dihydropyridines |
| JPS5965089A (ja) * | 1982-10-05 | 1984-04-13 | Shionogi & Co Ltd | ジヒドロピラゾロ〔３，４−ｂ〕ピリジン誘導体およびその製造法 |
-
1983
- 1983-12-02 GR GR73149A patent/GR79111B/el unknown
- 1983-12-06 AT AT83112273T patent/ATE69227T1/de not_active IP Right Cessation
- 1983-12-06 EP EP83112273A patent/EP0114273B1/en not_active Expired - Lifetime
- 1983-12-06 DE DE8383112273T patent/DE3382452D1/de not_active Expired - Fee Related
- 1983-12-07 ZA ZA839092A patent/ZA839092B/xx unknown
- 1983-12-09 AU AU22270/83A patent/AU574654B2/en not_active Ceased
- 1983-12-14 IL IL70445A patent/IL70445A/xx unknown
- 1983-12-16 DK DK582083A patent/DK582083A/da not_active Application Discontinuation
- 1983-12-19 JP JP58238063A patent/JPH0660181B2/ja not_active Expired - Lifetime
- 1983-12-19 IE IE2988/83A patent/IE57305B1/en not_active IP Right Cessation
- 1983-12-19 NZ NZ206626A patent/NZ206626A/en unknown
- 1983-12-19 NO NO834695A patent/NO160367C/no unknown
- 1983-12-19 KR KR1019830005999A patent/KR890002227B1/ko not_active Expired
- 1983-12-19 ES ES528152A patent/ES8601987A1/es not_active Expired
- 1983-12-19 PT PT77850A patent/PT77850B/pt not_active IP Right Cessation
- 1983-12-19 FI FI834661A patent/FI76337C/fi not_active IP Right Cessation
- 1983-12-20 PH PH30003A patent/PH20896A/en unknown
-
1984
- 1984-05-03 ES ES532124A patent/ES532124A0/es active Granted
-
1987
- 1987-06-18 MY MYPI87000836A patent/MY101250A/en unknown
-
1988
- 1988-12-20 US US07/286,917 patent/US4954508A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2227083A (en) | 1984-06-28 |
| IE832988L (en) | 1984-06-20 |
| KR840007000A (ko) | 1984-12-04 |
| DK582083A (da) | 1984-06-21 |
| JPS59118786A (ja) | 1984-07-09 |
| IL70445A (en) | 1988-12-30 |
| NZ206626A (en) | 1986-11-12 |
| NO160367B (no) | 1989-01-02 |
| ES8506016A1 (es) | 1985-06-16 |
| EP0114273A1 (en) | 1984-08-01 |
| AU574654B2 (en) | 1988-07-14 |
| FI76337B (fi) | 1988-06-30 |
| NO834695L (no) | 1984-06-21 |
| ATE69227T1 (de) | 1991-11-15 |
| PT77850B (en) | 1986-05-08 |
| EP0114273B1 (en) | 1991-11-06 |
| KR890002227B1 (ko) | 1989-06-24 |
| PH20896A (en) | 1987-05-27 |
| FI76337C (fi) | 1988-10-10 |
| IL70445A0 (en) | 1984-03-30 |
| ES528152A0 (es) | 1985-11-16 |
| GR79111B (en]) | 1984-10-02 |
| ES8601987A1 (es) | 1985-11-16 |
| FI834661A7 (fi) | 1984-06-21 |
| NO160367C (no) | 1989-04-12 |
| US4954508A (en) | 1990-09-04 |
| DE3382452D1 (de) | 1991-12-12 |
| PT77850A (en) | 1984-01-01 |
| ES532124A0 (es) | 1985-06-16 |
| IE57305B1 (en) | 1992-07-15 |
| DK582083D0 (da) | 1983-12-16 |
| FI834661A0 (fi) | 1983-12-19 |
| MY101250A (en) | 1991-08-17 |
| ZA839092B (en) | 1984-07-25 |
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