ES2365896T3 - Derivados de aril y heteroaril-piperidincarboxilatos, su preparación y su aplicación como inhibidores de la enzima faah. - Google Patents
Derivados de aril y heteroaril-piperidincarboxilatos, su preparación y su aplicación como inhibidores de la enzima faah. Download PDFInfo
- Publication number
- ES2365896T3 ES2365896T3 ES05732910T ES05732910T ES2365896T3 ES 2365896 T3 ES2365896 T3 ES 2365896T3 ES 05732910 T ES05732910 T ES 05732910T ES 05732910 T ES05732910 T ES 05732910T ES 2365896 T3 ES2365896 T3 ES 2365896T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- link
- pyridin
- cch2
- oxoethyl
- 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
- 238000002360 preparation method Methods 0.000 title claims description 8
- 101000918494 Homo sapiens Fatty-acid amide hydrolase 1 Proteins 0.000 title description 9
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000012453 solvate Substances 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 287
- -1 5-iso-butyl-pyridin-2-yl Chemical group 0.000 claims description 204
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 173
- 239000000203 mixture Substances 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 23
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 16
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 12
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 12
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 208000002193 Pain Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 238000007098 aminolysis reaction Methods 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
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- 208000030814 Eating disease Diseases 0.000 claims description 2
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- 230000004770 neurodegeneration Effects 0.000 claims description 2
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- 230000001131 transforming effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- 239000007864 aqueous solution Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 17
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 8
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 102100027297 Fatty acid 2-hydroxylase Human genes 0.000 description 4
- 101000937693 Homo sapiens Fatty acid 2-hydroxylase Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 201000002661 Spondylitis Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 125000001153 fluoro group Chemical group F* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- PBYMYAJONQZORL-UHFFFAOYSA-N 1-methylisoquinoline Chemical compound C1=CC=C2C(C)=NC=CC2=C1 PBYMYAJONQZORL-UHFFFAOYSA-N 0.000 description 2
- RCRCTBLIHCHWDZ-UHFFFAOYSA-N 2-Arachidonoyl Glycerol Chemical compound CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO RCRCTBLIHCHWDZ-UHFFFAOYSA-N 0.000 description 2
- DFWQMXIQQKCGCY-UHFFFAOYSA-N 4-(4-bromophenyl)-4-hydroxypiperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1(O)C1=CC=C(Br)C=C1 DFWQMXIQQKCGCY-UHFFFAOYSA-N 0.000 description 2
- RGAFXEOPVNUDMQ-UHFFFAOYSA-N 4-(4-phenylimidazol-1-yl)piperidine Chemical compound C1CNCCC1N1C=C(C=2C=CC=CC=2)N=C1 RGAFXEOPVNUDMQ-UHFFFAOYSA-N 0.000 description 2
- BNMDUCFDNPEQLU-UHFFFAOYSA-N 4-(naphthalen-2-ylmethyl)piperidine Chemical compound C=1C=C2C=CC=CC2=CC=1CC1CCNCC1 BNMDUCFDNPEQLU-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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- 150000007513 acids Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
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- 206010003246 arthritis Diseases 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- RSMNYTJCWIDZAH-UHFFFAOYSA-N tert-butyl 4-(iodomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CI)CC1 RSMNYTJCWIDZAH-UHFFFAOYSA-N 0.000 description 2
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- ADQSJCUTSIHZHC-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl) 4-(2-isoquinolin-1-ylethyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC(=O)OCC)CCC1CCC1=NC=CC2=CC=CC=C12 ADQSJCUTSIHZHC-UHFFFAOYSA-N 0.000 description 1
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- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
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- SEULWJSKCVACTH-UHFFFAOYSA-N 1-phenylimidazole Chemical compound C1=NC=CN1C1=CC=CC=C1 SEULWJSKCVACTH-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 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
- C07D211/36—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 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- C07D211/10—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
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- C07D—HETEROCYCLIC COMPOUNDS
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- 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
- C07D211/36—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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Virology (AREA)
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- Ophthalmology & Optometry (AREA)
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- Anesthesiology (AREA)
- Otolaryngology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0401950 | 2004-02-26 | ||
| FR0401950A FR2866884B1 (fr) | 2004-02-26 | 2004-02-26 | Derives d'aryl-et d'heteroaryl-piperidinecarboxylates, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2365896T3 true ES2365896T3 (es) | 2011-10-13 |
Family
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Family Applications (1)
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| EP (1) | EP1720872B1 (https=) |
| JP (1) | JP4812745B2 (https=) |
| KR (1) | KR20060134080A (https=) |
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| AU (1) | AU2005223424B2 (https=) |
| BR (1) | BRPI0508103A (https=) |
| CA (1) | CA2554610A1 (https=) |
| CY (1) | CY1111706T1 (https=) |
| DE (1) | DE602005027546D1 (https=) |
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| FR (1) | FR2866884B1 (https=) |
| IL (1) | IL177326A (https=) |
| MA (1) | MA28365A1 (https=) |
| NO (1) | NO20064326L (https=) |
| NZ (1) | NZ550006A (https=) |
| PL (1) | PL1720872T3 (https=) |
| PT (1) | PT1720872E (https=) |
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| SI (1) | SI1720872T1 (https=) |
| TW (1) | TWI353834B (https=) |
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| FR2866888B1 (fr) * | 2004-02-26 | 2006-05-05 | Sanofi Synthelabo | Derives de alkylpiperazine- et alkylhomopiperazine- carboxylates, leur preparation et leur application en therapeutique |
| US7269708B2 (en) * | 2004-04-20 | 2007-09-11 | Rambus Inc. | Memory controller for non-homogenous memory system |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| ES2528674T3 (es) | 2005-02-17 | 2015-02-11 | Astellas Pharma Inc. | Piperidina y carboxilatos de piperacina como inhibidores de FAAH |
| US7918848B2 (en) | 2005-03-25 | 2011-04-05 | Maquet Cardiovascular, Llc | Tissue welding and cutting apparatus and method |
| US8197472B2 (en) | 2005-03-25 | 2012-06-12 | Maquet Cardiovascular, Llc | Tissue welding and cutting apparatus and method |
| PE20070099A1 (es) | 2005-06-30 | 2007-02-06 | Janssen Pharmaceutica Nv | N-heteroarilpiperazinil ureas como moduladores de la amida hidrolasa del acido graso |
| US20110172230A1 (en) * | 2006-08-23 | 2011-07-14 | Takahiro Ishii | Urea compound or salt thereof |
| AU2007292155B2 (en) | 2006-09-05 | 2012-11-01 | Kyowa Kirin Co., Ltd. | Imidazole derivative |
| PT2178858E (pt) | 2007-08-02 | 2012-02-24 | Recordati Ireland Ltd | Novos compostos heterocíclicos como antagonistas de mglu5 |
| BRPI0818338A2 (pt) | 2007-10-16 | 2015-04-22 | Daiichi Sankyo Co Ltd | Composto de pirimidil indolina |
| HUE025411T2 (en) * | 2008-03-04 | 2016-02-29 | Vernalis R&D Ltd | azetidine |
| TW200948805A (en) * | 2008-03-07 | 2009-12-01 | Sigma Tau Ind Farmaceuti | Enol carbamate derivatives as modulators of fatty acid amide hydrolase |
| JP2011521723A (ja) | 2008-05-27 | 2011-07-28 | マッケ カーディオバスキュラー，エルエルシー | 外科用器具および方法 |
| US9968396B2 (en) | 2008-05-27 | 2018-05-15 | Maquet Cardiovascular Llc | Surgical instrument and method |
| US9402680B2 (en) | 2008-05-27 | 2016-08-02 | Maquet Cardiovasular, Llc | Surgical instrument and method |
| TWI434842B (zh) * | 2008-07-14 | 2014-04-21 | Astellas Pharma Inc | Azole compounds |
| FR2945531A1 (fr) * | 2009-05-12 | 2010-11-19 | Sanofi Aventis | Derives de 7-aza-spiro°3,5!nonane-7-carboxylates, leur preparation et leur application en therapeutique |
| FR2945533B1 (fr) * | 2009-05-12 | 2011-05-27 | Sanofi Aventis | Derives de cyclopenta°c!pyrrolyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| TW201044234A (en) * | 2009-06-08 | 2010-12-16 | Chunghwa Picture Tubes Ltd | Method of scanning touch panel |
| US9955858B2 (en) | 2009-08-21 | 2018-05-01 | Maquet Cardiovascular Llc | Surgical instrument and method for use |
| SG182567A1 (en) | 2010-01-20 | 2012-08-30 | Sanofi Sa | Alkyl-heterocycle carbamate derivatives, their preparation and their therapeutic application |
| FR2955325B1 (fr) * | 2010-01-20 | 2012-01-20 | Sanofi Aventis | Derives de carbamates d'alkyl-heterocycles, leur preparation et leur application en therapeutique |
| FR2955580A1 (fr) * | 2010-01-28 | 2011-07-29 | Sanofi Aventis | Derives de carbamate d'alkyl-heterocycles, leur preparation et leur application en therapeutique |
| JP2013147430A (ja) * | 2010-04-28 | 2013-08-01 | Astellas Pharma Inc | 夜間頻尿の予防又は治療剤 |
| TW201206440A (en) * | 2010-04-28 | 2012-02-16 | Astellas Pharma Inc | Prophylactic or therapeutic agent for diseases associated with pains in urinary organs |
| DE102012018115A1 (de) | 2012-09-13 | 2014-03-13 | Matthias Lehr | Aryl-N-(arylalkyl)carbamate als Hemmstoffe der Fatty Acid Amide Hydrolase |
| WO2014054635A1 (ja) * | 2012-10-02 | 2014-04-10 | 大日本住友製薬株式会社 | イミダゾール誘導体 |
| DE102013016573A1 (de) | 2013-10-04 | 2015-04-09 | Matthias Lehr | 1-Tetrazolylpropan-2-one als Inhibitoren von cytosolischer Phospholipase A2 und Fatty Acid Amide Hydrolase, insbesondere geeignet zur topischen Anwendung |
| WO2019185708A1 (en) | 2018-03-28 | 2019-10-03 | Georg-August-Universitaet Goettingen, Stiftung Oeffentlichen Rechts, Universitaetsmedizin | Prevention or treatment of chronic organ injury |
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| JP2001523695A (ja) * | 1997-11-24 | 2001-11-27 | ザ スクリップス リサーチ インスティテュート | ギャップ結合連絡の阻害剤 |
| MXPA03009850A (es) * | 2001-04-27 | 2004-02-12 | Bristol Myers Squibb Co | Inhibidores de bisarilimidazolil de hidrolasa de amida del acido graso. |
| US6982263B2 (en) * | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
| FR2843964B1 (fr) * | 2002-08-29 | 2004-10-01 | Sanofi Synthelabo | Derives de dioxane-2-alkylcarbamates, leur preparation et leur application en therapeutique |
| FR2850377B1 (fr) * | 2003-01-23 | 2009-02-20 | Sanofi Synthelabo | Derives d'arylalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2854633B1 (fr) * | 2003-05-07 | 2005-06-24 | Sanofi Synthelabo | Derives de piperidinyl-et piperazinyl-alkylcarbamates, leur preparation et leur application en therapeutique |
| FR2865205B1 (fr) * | 2004-01-16 | 2006-02-24 | Sanofi Synthelabo | Derives de type aryloxyalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2866886B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-akylcarbamates, leur preparation et leur application en therapeutique |
| FR2866885B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives de piperidinylalkylcarbamates, leur prepation et leur application en therapeutique |
| FR2866888B1 (fr) * | 2004-02-26 | 2006-05-05 | Sanofi Synthelabo | Derives de alkylpiperazine- et alkylhomopiperazine- carboxylates, leur preparation et leur application en therapeutique |
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- 2005-02-25 CA CA002554610A patent/CA2554610A1/fr not_active Abandoned
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- 2005-02-25 EP EP05732910A patent/EP1720872B1/fr not_active Expired - Lifetime
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- 2005-02-25 WO PCT/FR2005/000453 patent/WO2005090347A1/fr not_active Ceased
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2011
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