PT1594859E - INDAZOLAMIDAS COM ACTIVIDADE ANALGéSICA - Google Patents
INDAZOLAMIDAS COM ACTIVIDADE ANALGéSICA Download PDFInfo
- Publication number
- PT1594859E PT1594859E PT04705070T PT04705070T PT1594859E PT 1594859 E PT1594859 E PT 1594859E PT 04705070 T PT04705070 T PT 04705070T PT 04705070 T PT04705070 T PT 04705070T PT 1594859 E PT1594859 E PT 1594859E
- Authority
- PT
- Portugal
- Prior art keywords
- methyl
- indazolamide
- pharmaceutically acceptable
- compound
- indazole
- Prior art date
Links
- DITBWPUMEUDVLU-UHFFFAOYSA-N 1h-indazole-3-carboxamide Chemical class C1=CC=C2C(C(=O)N)=NNC2=C1 DITBWPUMEUDVLU-UHFFFAOYSA-N 0.000 title claims description 30
- 230000000202 analgesic effect Effects 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 36
- -1 acetylamino, sulfonylmethyl Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 10
- 239000011707 mineral Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- BHXVYTQDWMQVBI-UHFFFAOYSA-N 1h-indazole-3-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=NNC2=C1 BHXVYTQDWMQVBI-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- GSMGZEUTNQHFTE-UHFFFAOYSA-N n-[[1-(2-anilino-2-oxoethyl)piperidin-4-yl]methyl]-5-methyl-1h-indazole-3-carboxamide Chemical compound C12=CC(C)=CC=C2NN=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=CC=C1 GSMGZEUTNQHFTE-UHFFFAOYSA-N 0.000 claims description 2
- QKJUBZQAEXBFSR-UHFFFAOYSA-N n-[[1-[2-(4-nitroanilino)-2-oxoethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=C([N+]([O-])=O)C=C1 QKJUBZQAEXBFSR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- 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 claims 5
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- YOBPGAAXNZXKOO-UHFFFAOYSA-N n-[[1-(2-anilino-2-oxoethyl)piperidin-4-yl]methyl]-1-benzylindazole-3-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)CN(CC1)CCC1CNC(=O)C(C1=CC=CC=C11)=NN1CC1=CC=CC=C1 YOBPGAAXNZXKOO-UHFFFAOYSA-N 0.000 claims 1
- YWAMRUDZAIUOIR-UHFFFAOYSA-N n-[[1-(2-anilino-2-oxoethyl)piperidin-4-yl]methyl]-1h-indazole-3-carboxamide Chemical compound C1CC(CNC(=O)C=2C3=CC=CC=C3NN=2)CCN1CC(=O)NC1=CC=CC=C1 YWAMRUDZAIUOIR-UHFFFAOYSA-N 0.000 claims 1
- DSRHMZBSHNFUPM-UHFFFAOYSA-N n-[[1-[2-(4-aminoanilino)-2-oxoethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=C(N)C=C1 DSRHMZBSHNFUPM-UHFFFAOYSA-N 0.000 claims 1
- FKCRLJHNUSANDH-UHFFFAOYSA-N n-[[1-[2-[4-(dimethylamino)anilino]-2-oxoethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide Chemical group C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=C(N(C)C)C=C1 FKCRLJHNUSANDH-UHFFFAOYSA-N 0.000 claims 1
- GGSFMCZQYJYCDK-UHFFFAOYSA-N n-[[1-[2-oxo-2-(4-phenylmethoxyanilino)ethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC(C=C1)=CC=C1OCC1=CC=CC=C1 GGSFMCZQYJYCDK-UHFFFAOYSA-N 0.000 claims 1
- 150000003891 oxalate salts Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 239000000047 product Substances 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 208000002193 Pain Diseases 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 208000004454 Hyperalgesia Diseases 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
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- 241000700159 Rattus Species 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
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- 239000000243 solution Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
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- 208000000094 Chronic Pain Diseases 0.000 description 7
- 208000000114 Pain Threshold Diseases 0.000 description 7
- 230000037040 pain threshold Effects 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 6
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- 208000004296 neuralgia Diseases 0.000 description 5
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- 238000001953 recrystallisation Methods 0.000 description 5
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 4
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- 241000699670 Mus sp. Species 0.000 description 4
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
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- 239000007832 Na2SO4 Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000370 acceptor Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- OIDPZJIQEKYCSH-UHFFFAOYSA-N 2-[4-(aminomethyl)piperidin-1-yl]-n-phenylacetamide;dihydrochloride Chemical compound Cl.Cl.C1CC(CN)CCN1CC(=O)NC1=CC=CC=C1 OIDPZJIQEKYCSH-UHFFFAOYSA-N 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
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- OVYVGHSZKGWWEC-UHFFFAOYSA-N n-[[1-(2-anilino-2-oxoethyl)piperidin-4-yl]methyl]-5-methyl-1-propan-2-ylindazole-3-carboxamide;hydrochloride Chemical compound Cl.C12=CC(C)=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=CC=C1 OVYVGHSZKGWWEC-UHFFFAOYSA-N 0.000 description 2
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- 230000007170 pathology Effects 0.000 description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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- CDRCOZFGMPTGBL-UHFFFAOYSA-N 1-benzylindazole-3-carboxylic acid Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=CC=C1 CDRCOZFGMPTGBL-UHFFFAOYSA-N 0.000 description 1
- HWMBORXKBCINOU-UHFFFAOYSA-N 2-[4-(aminomethyl)piperidin-1-yl]-n-phenylacetamide Chemical compound C1CC(CN)CCN1CC(=O)NC1=CC=CC=C1 HWMBORXKBCINOU-UHFFFAOYSA-N 0.000 description 1
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- PUTGNXQFFCKNKT-UHFFFAOYSA-N n-[[1-[2-(4-aminoanilino)-2-oxoethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide;dihydrochloride Chemical compound Cl.Cl.C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=C(N)C=C1 PUTGNXQFFCKNKT-UHFFFAOYSA-N 0.000 description 1
- OYCDJAIXOWQZER-UHFFFAOYSA-N n-[[1-[2-(4-hydroxyanilino)-2-oxoethyl]piperidin-4-yl]methyl]-1-propan-2-ylindazole-3-carboxamide;hydrochloride Chemical compound Cl.C12=CC=CC=C2N(C(C)C)N=C1C(=O)NCC(CC1)CCN1CC(=O)NC1=CC=C(O)C=C1 OYCDJAIXOWQZER-UHFFFAOYSA-N 0.000 description 1
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- DBMHTLOVZSDLFD-UHFFFAOYSA-N piperidin-1-ylmethanamine Chemical compound NCN1CCCCC1 DBMHTLOVZSDLFD-UHFFFAOYSA-N 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT000287A ITMI20030287A1 (it) | 2003-02-18 | 2003-02-18 | Indazolammidi dotate di attivita' analgesica metodo, per |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1594859E true PT1594859E (pt) | 2010-07-23 |
Family
ID=32894157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT04705070T PT1594859E (pt) | 2003-02-18 | 2004-01-26 | INDAZOLAMIDAS COM ACTIVIDADE ANALGéSICA |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US7632849B2 (https=) |
| EP (1) | EP1594859B1 (https=) |
| JP (1) | JP4724651B2 (https=) |
| KR (1) | KR101108222B1 (https=) |
| CN (2) | CN101139341B (https=) |
| AR (1) | AR043186A1 (https=) |
| AT (1) | ATE471934T1 (https=) |
| AU (1) | AU2004213104B2 (https=) |
| CA (1) | CA2511984C (https=) |
| DE (1) | DE602004027792D1 (https=) |
| DK (1) | DK1594859T3 (https=) |
| EA (1) | EA009077B1 (https=) |
| ES (1) | ES2345983T3 (https=) |
| GE (1) | GEP20074075B (https=) |
| IL (1) | IL169285A (https=) |
| IT (1) | ITMI20030287A1 (https=) |
| MX (1) | MXPA05008730A (https=) |
| PL (1) | PL215870B1 (https=) |
| PT (1) | PT1594859E (https=) |
| SI (1) | SI1594859T1 (https=) |
| UA (1) | UA79537C2 (https=) |
| WO (1) | WO2004074275A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20031468A1 (it) * | 2003-07-18 | 2005-01-19 | Acraf | Farmaco ativo nel dolore neuropatico |
| WO2005123718A2 (en) * | 2004-06-15 | 2005-12-29 | Pfizer Japan Inc. | Benzimidazolone carboxylic acid derivatives |
| CN102046240B (zh) * | 2008-03-25 | 2014-06-25 | 阿费克蒂斯药品公司 | 新的p2x7r拮抗剂及其应用 |
| US8815892B2 (en) | 2008-03-25 | 2014-08-26 | Affectis Pharmaceuticals Ag | P2X7R antagonists and their use |
| WO2010118921A1 (en) * | 2009-04-14 | 2010-10-21 | Affectis Pharmaceuticals Ag | Novel p2x7r antagonists and their use |
| CA2860250C (en) * | 2012-02-21 | 2020-11-10 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors |
| RS54539B1 (sr) | 2012-02-21 | 2016-06-30 | Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - S.P.A. | Upotreba 1h-indazol-3-karboksamidnih jedinjenja kao inhibitora kinaze 3-beta glikogen sintetaze |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| JP6064062B2 (ja) | 2013-03-15 | 2017-01-18 | ファイザー・インク | Ａｍｐｋを活性化させるインダゾール化合物 |
| PT3790873T (pt) | 2018-05-07 | 2022-05-11 | Acraf | Compostos de 1h-indazole-3-carboxamida como inibidores da glicogénio sintase cinase 3 beta |
| CN109336890B (zh) * | 2018-11-17 | 2020-03-20 | 重庆文理学院 | 一种吲唑类衍生物的合成方法及抗肿瘤应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3705175A (en) * | 1969-04-01 | 1972-12-05 | Egyt Gyogyszervegyeszeti Gyar | Indazole-3-carboxylic amides |
| US5654320A (en) * | 1995-03-16 | 1997-08-05 | Eli Lilly And Company | Indazolecarboxamides |
| IL117438A (en) * | 1995-03-16 | 2001-12-23 | Lilly Co Eli | Indazolecarboxamides, their preparation and pharmaceutical compositions containing them |
| EP0829474B1 (en) * | 1995-05-31 | 2003-04-09 | Nisshin Seifun Group Inc. | Indazole derivatives having monocyclic amino group |
| EP0802067B1 (en) * | 1995-11-08 | 2002-04-24 | Toray Industries, Inc. | Direct drawing type waterless planographic original form plate |
| JP3911297B2 (ja) | 1996-08-16 | 2007-05-09 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | Ｎ―［（１―ｎブチル―４―ピペリジル）メチル］―３，４―ジヒドロ―２Ｈ―［１，３］オキサジノ［３，２―ａ］インドール―１０―カルボキシアミドおよび塩ならびに製造における中間体 |
| IT1291569B1 (it) | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolammidi come agenti serotoninergici |
| US6339087B1 (en) * | 1997-08-18 | 2002-01-15 | Syntex (U.S.A.) Llc | Cyclic amine derivatives-CCR-3 receptor antagonists |
| US6069152A (en) * | 1997-10-07 | 2000-05-30 | Eli Lilly And Company | 5-HT4 agonists and antagonists |
| DE69940951D1 (de) * | 1998-04-21 | 2009-07-16 | Bristol Myers Squibb Pharma Co | Nd wachstumshemmende mittel |
| US6407103B2 (en) * | 1998-04-21 | 2002-06-18 | Bristol-Myers Squibb Pharma Company | Indeno [1,2-c] pyrazol-4-ones and their uses |
-
2003
- 2003-02-18 IT IT000287A patent/ITMI20030287A1/it unknown
-
2004
- 2004-01-26 KR KR1020057014055A patent/KR101108222B1/ko not_active Expired - Fee Related
- 2004-01-26 GE GEAP20048983A patent/GEP20074075B/en unknown
- 2004-01-26 CA CA2511984A patent/CA2511984C/en not_active Expired - Fee Related
- 2004-01-26 PL PL377236A patent/PL215870B1/pl unknown
- 2004-01-26 PT PT04705070T patent/PT1594859E/pt unknown
- 2004-01-26 WO PCT/EP2004/000647 patent/WO2004074275A1/en not_active Ceased
- 2004-01-26 EA EA200501164A patent/EA009077B1/ru not_active IP Right Cessation
- 2004-01-26 EP EP04705070A patent/EP1594859B1/en not_active Expired - Lifetime
- 2004-01-26 MX MXPA05008730A patent/MXPA05008730A/es active IP Right Grant
- 2004-01-26 DK DK04705070.3T patent/DK1594859T3/da active
- 2004-01-26 SI SI200431488T patent/SI1594859T1/sl unknown
- 2004-01-26 US US10/541,209 patent/US7632849B2/en not_active Expired - Fee Related
- 2004-01-26 AT AT04705070T patent/ATE471934T1/de active
- 2004-01-26 CN CN2007101801011A patent/CN101139341B/zh not_active Expired - Fee Related
- 2004-01-26 AU AU2004213104A patent/AU2004213104B2/en not_active Ceased
- 2004-01-26 ES ES04705070T patent/ES2345983T3/es not_active Expired - Lifetime
- 2004-01-26 UA UAA200508163A patent/UA79537C2/uk unknown
- 2004-01-26 CN CNB2004800025681A patent/CN100347168C/zh not_active Expired - Fee Related
- 2004-01-26 JP JP2006501608A patent/JP4724651B2/ja not_active Expired - Fee Related
- 2004-01-26 DE DE602004027792T patent/DE602004027792D1/de not_active Expired - Lifetime
- 2004-02-16 AR ARP040100467A patent/AR043186A1/es not_active Application Discontinuation
-
2005
- 2005-06-20 IL IL169285A patent/IL169285A/en not_active IP Right Cessation
-
2009
- 2009-10-28 US US12/607,463 patent/US8519139B2/en not_active Expired - Fee Related
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