CA2238430C - Pyrazole derivatives, method for preparing same, and pharmaceutical compositions containing said derivatives - Google Patents
Pyrazole derivatives, method for preparing same, and pharmaceutical compositions containing said derivatives Download PDFInfo
- Publication number
- CA2238430C CA2238430C CA002238430A CA2238430A CA2238430C CA 2238430 C CA2238430 C CA 2238430C CA 002238430 A CA002238430 A CA 002238430A CA 2238430 A CA2238430 A CA 2238430A CA 2238430 C CA2238430 C CA 2238430C
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- Prior art keywords
- formula
- compound
- alkoxy
- alkyl
- treated
- 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 - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 24
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- 150000003217 pyrazoles Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 106
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 102000018208 Cannabinoid Receptor Human genes 0.000 claims abstract description 13
- 108050007331 Cannabinoid receptor Proteins 0.000 claims abstract description 13
- 239000011737 fluorine Substances 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical group 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims abstract description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 4
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 13
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 239000003446 ligand Substances 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 4
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
- 239000002243 precursor Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000006715 (C1-C5) alkylthio group Chemical group 0.000 claims 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- 239000000047 product Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
- -1 hexahydroazepin-1-yl Chemical group 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 229910052792 caesium Inorganic materials 0.000 description 8
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 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 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000004342 Benzoyl peroxide Substances 0.000 description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 150000002832 nitroso derivatives Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011698 potassium fluoride Substances 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000012025 fluorinating agent Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 235000003270 potassium fluoride Nutrition 0.000 description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 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
- ZLSDEVRDASOICE-UHFFFAOYSA-N 2-azaadamantane Chemical compound C1C(N2)CC3CC1CC2C3 ZLSDEVRDASOICE-UHFFFAOYSA-N 0.000 description 2
- IYTILBYEKJRMDR-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(2-hydroxyethoxymethyl)pyrazole-3-carboxylic acid Chemical compound OCCOCC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 IYTILBYEKJRMDR-UHFFFAOYSA-N 0.000 description 2
- NTWAYMOWNWGBMM-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(fluoromethyl)pyrazole-3-carboxylic acid Chemical compound FCC=1C(C(=O)O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 NTWAYMOWNWGBMM-UHFFFAOYSA-N 0.000 description 2
- DNVCITOWHKQMKF-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(methylsulfanylmethyl)pyrazole-3-carboxylic acid Chemical compound CSCC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 DNVCITOWHKQMKF-UHFFFAOYSA-N 0.000 description 2
- JCUUXEGZNQKVDJ-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(methylsulfonylmethyl)pyrazole-3-carboxylic acid Chemical compound CS(=O)(=O)CC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JCUUXEGZNQKVDJ-UHFFFAOYSA-N 0.000 description 2
- CYAYCOCJAVHQSD-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid Chemical compound CC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 CYAYCOCJAVHQSD-UHFFFAOYSA-N 0.000 description 2
- FVZNNMHOCOQVSD-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-(cyanomethyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylic acid Chemical compound N#CCC=1C(C(=O)O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 FVZNNMHOCOQVSD-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- NDYWSWDCOWRLOQ-UHFFFAOYSA-N CCN(CC)SN(CC)CC.F.F.F Chemical compound CCN(CC)SN(CC)CC.F.F.F NDYWSWDCOWRLOQ-UHFFFAOYSA-N 0.000 description 2
- 229940122820 Cannabinoid receptor antagonist Drugs 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-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
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 239000003536 cannabinoid receptor antagonist Substances 0.000 description 2
- 239000008139 complexing agent Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 238000002372 labelling Methods 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
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- CXCDAZCCJPKEFY-UHFFFAOYSA-N methyl 4-(bromomethyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)pyrazole-3-carboxylate Chemical compound BrCC=1C(C(=O)OC)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 CXCDAZCCJPKEFY-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- PCZOZSATUTWXIC-UHFFFAOYSA-N tetraethylazanium;cyanide Chemical compound N#[C-].CC[N+](CC)(CC)CC PCZOZSATUTWXIC-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZLIZZDCWMOGEGA-UHFFFAOYSA-N 1h-pyrazole-5-carbonyl chloride Chemical compound ClC(=O)C=1C=CNN=1 ZLIZZDCWMOGEGA-UHFFFAOYSA-N 0.000 description 1
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-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
- YFCFVWOVLFMIOB-UHFFFAOYSA-N 2-hydroxyethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(2-hydroxyethoxymethyl)pyrazole-3-carboxylate Chemical compound OCCOCC=1C(C(=O)OCCO)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 YFCFVWOVLFMIOB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D231/14—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
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- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9513956A FR2741621B1 (fr) | 1995-11-23 | 1995-11-23 | Nouveaux derives de pyrazole, procede pour leur preparation et compositions pharmaceutiques en contenant |
| FR95/13956 | 1995-11-23 | ||
| PCT/FR1996/001847 WO1997019063A1 (fr) | 1995-11-23 | 1996-11-21 | Derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2238430A1 CA2238430A1 (en) | 1997-05-29 |
| CA2238430C true CA2238430C (en) | 2006-05-09 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002238430A Expired - Fee Related CA2238430C (en) | 1995-11-23 | 1996-11-21 | Pyrazole derivatives, method for preparing same, and pharmaceutical compositions containing said derivatives |
Country Status (16)
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| US (1) | US6028084A (enExample) |
| EP (1) | EP0876350B1 (enExample) |
| JP (1) | JP2000500479A (enExample) |
| AT (1) | ATE203015T1 (enExample) |
| AU (1) | AU7698596A (enExample) |
| BR (1) | BR9611618A (enExample) |
| CA (1) | CA2238430C (enExample) |
| DE (1) | DE69613860T2 (enExample) |
| DK (1) | DK0876350T3 (enExample) |
| ES (1) | ES2161382T3 (enExample) |
| FR (1) | FR2741621B1 (enExample) |
| GR (1) | GR3036830T3 (enExample) |
| MX (1) | MX9803891A (enExample) |
| NO (1) | NO310508B1 (enExample) |
| PT (1) | PT876350E (enExample) |
| WO (1) | WO1997019063A1 (enExample) |
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Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3449350A (en) * | 1968-06-24 | 1969-06-10 | Ciba Geigy Corp | Certain pyrazole-3-carboxylic acid hydrazide derivatives |
| FR2665898B1 (fr) * | 1990-08-20 | 1994-03-11 | Sanofi | Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FR2692575B1 (fr) * | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| FR2713225B1 (fr) * | 1993-12-02 | 1996-03-01 | Sanofi Sa | N-pipéridino-3-pyrazolecarboxamide substitué. |
| FR2711140B1 (fr) * | 1993-10-12 | 1996-01-05 | Sanofi Sa | 1-Naphtylpyrazole-3-carboxamides substitués actifs sur la neurotensine, leur préparation, les compositions pharmaceutiques en contenant. |
| FR2714057B1 (fr) * | 1993-12-17 | 1996-03-08 | Sanofi Elf | Nouveaux dérivés du 3-pyrazolecarboxamide, procédé pour leur préparation et compositions pharmaceutiques les contenant. |
-
1995
- 1995-11-23 FR FR9513956A patent/FR2741621B1/fr not_active Expired - Fee Related
-
1996
- 1996-11-21 EP EP96939962A patent/EP0876350B1/fr not_active Expired - Lifetime
- 1996-11-21 AU AU76985/96A patent/AU7698596A/en not_active Abandoned
- 1996-11-21 WO PCT/FR1996/001847 patent/WO1997019063A1/fr not_active Ceased
- 1996-11-21 PT PT96939962T patent/PT876350E/pt unknown
- 1996-11-21 US US09/068,869 patent/US6028084A/en not_active Expired - Lifetime
- 1996-11-21 BR BR9611618A patent/BR9611618A/pt not_active Application Discontinuation
- 1996-11-21 DE DE69613860T patent/DE69613860T2/de not_active Expired - Lifetime
- 1996-11-21 ES ES96939962T patent/ES2161382T3/es not_active Expired - Lifetime
- 1996-11-21 AT AT96939962T patent/ATE203015T1/de not_active IP Right Cessation
- 1996-11-21 JP JP9519454A patent/JP2000500479A/ja active Pending
- 1996-11-21 CA CA002238430A patent/CA2238430C/en not_active Expired - Fee Related
- 1996-11-21 DK DK96939962T patent/DK0876350T3/da active
-
1998
- 1998-05-15 MX MX9803891A patent/MX9803891A/es unknown
- 1998-05-22 NO NO19982330A patent/NO310508B1/no unknown
-
2001
- 2001-10-08 GR GR20010401691T patent/GR3036830T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| MX9803891A (es) | 1998-09-30 |
| NO982330L (no) | 1998-05-22 |
| EP0876350B1 (fr) | 2001-07-11 |
| GR3036830T3 (en) | 2002-01-31 |
| NO982330D0 (no) | 1998-05-22 |
| WO1997019063A1 (fr) | 1997-05-29 |
| BR9611618A (pt) | 1999-03-30 |
| US6028084A (en) | 2000-02-22 |
| FR2741621B1 (fr) | 1998-02-13 |
| AU7698596A (en) | 1997-06-11 |
| FR2741621A1 (fr) | 1997-05-30 |
| ATE203015T1 (de) | 2001-07-15 |
| JP2000500479A (ja) | 2000-01-18 |
| DE69613860D1 (de) | 2001-08-16 |
| CA2238430A1 (en) | 1997-05-29 |
| DE69613860T2 (de) | 2002-04-04 |
| DK0876350T3 (da) | 2001-11-05 |
| NO310508B1 (no) | 2001-07-16 |
| EP0876350A1 (fr) | 1998-11-11 |
| ES2161382T3 (es) | 2001-12-01 |
| PT876350E (pt) | 2001-12-28 |
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