IL171694A - Derivatives of piperidinyl-and piperazinyl-alkyl carbamates, process for preparation thereof, pharmaceutical compositions comprising said derivatives and use of said derivatives for the preparation of medicaments - Google Patents
Derivatives of piperidinyl-and piperazinyl-alkyl carbamates, process for preparation thereof, pharmaceutical compositions comprising said derivatives and use of said derivatives for the preparation of medicamentsInfo
- Publication number
- IL171694A IL171694A IL171694A IL17169405A IL171694A IL 171694 A IL171694 A IL 171694A IL 171694 A IL171694 A IL 171694A IL 17169405 A IL17169405 A IL 17169405A IL 171694 A IL171694 A IL 171694A
- Authority
- IL
- Israel
- Prior art keywords
- group
- mmol
- piperidyl
- general formula
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 67
- 230000008569 process Effects 0.000 title description 40
- 238000002360 preparation method Methods 0.000 title description 12
- 239000008194 pharmaceutical composition Substances 0.000 title description 5
- 239000003814 drug Substances 0.000 title description 3
- -1 tetrahydroquinolyl Chemical group 0.000 claims description 88
- 150000001875 compounds Chemical class 0.000 claims description 73
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052731 fluorine Chemical group 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
- 125000005493 quinolyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 8
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 8
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000007098 aminolysis reaction Methods 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 5
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000005390 cinnolyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 4
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 125000002785 azepinyl group Chemical group 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 150000001475 oxazolidinediones Chemical class 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- 239000002585 base Substances 0.000 description 80
- 239000000203 mixture Substances 0.000 description 72
- 239000000243 solution Substances 0.000 description 67
- 239000000047 product Substances 0.000 description 62
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 238000004587 chromatography analysis Methods 0.000 description 46
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 17
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
- LDSQQXKSEFZAPE-UHFFFAOYSA-N 2-piperidin-4-ylethanol Chemical compound OCCC1CCNCC1 LDSQQXKSEFZAPE-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 8
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 description 8
- 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 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 4
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 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 4
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229940031098 ethanolamine Drugs 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- PDUKMGYSTJLETD-UHFFFAOYSA-N 3-[2-(1-quinolin-2-ylpiperidin-4-yl)ethyl]-1,3-oxazolidine-2,4-dione Chemical compound O=C1COC(=O)N1CCC1CCN(C=2N=C3C=CC=CC3=CC=2)CC1 PDUKMGYSTJLETD-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 201000002661 Spondylitis Diseases 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940126601 medicinal product Drugs 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- JTMPFBWINFTYPA-UHFFFAOYSA-N (2-amino-2-oxoethyl) n-[2-[1-(6-chloroquinolin-2-yl)piperidin-4-yl]ethyl]carbamate Chemical compound C1CC(CCNC(=O)OCC(=O)N)CCN1C1=CC=C(C=C(Cl)C=C2)C2=N1 JTMPFBWINFTYPA-UHFFFAOYSA-N 0.000 description 2
- VPDZSICWTOYASA-UHFFFAOYSA-N 1-[4-(2-chloroethyl)piperidin-1-yl]isoquinoline Chemical compound C1CC(CCCl)CCN1C1=NC=CC2=CC=CC=C12 VPDZSICWTOYASA-UHFFFAOYSA-N 0.000 description 2
- MSQCQINLJMEVNJ-UHFFFAOYSA-N 1-chloroisoquinoline Chemical compound C1=CC=C2C(Cl)=NC=CC2=C1 MSQCQINLJMEVNJ-UHFFFAOYSA-N 0.000 description 2
- KUBHDLMBPRZQKH-UHFFFAOYSA-N 2-(1-isoquinolin-1-ylpiperidin-4-yl)ethanol Chemical compound C1CC(CCO)CCN1C1=NC=CC2=CC=CC=C12 KUBHDLMBPRZQKH-UHFFFAOYSA-N 0.000 description 2
- OLRHVCVJRVJYSE-UHFFFAOYSA-N 2-(1-isoquinolin-3-ylpiperidin-4-yl)ethanol Chemical compound C1CC(CCO)CCN1C1=CC2=CC=CC=C2C=N1 OLRHVCVJRVJYSE-UHFFFAOYSA-N 0.000 description 2
- IDTRMCJZUBPLSD-UHFFFAOYSA-N 2-(1-isoquinolin-4-ylpiperidin-4-yl)ethanol Chemical compound C1CC(CCO)CCN1C1=CN=CC2=CC=CC=C12 IDTRMCJZUBPLSD-UHFFFAOYSA-N 0.000 description 2
- XCWSQWUAQCIMKH-UHFFFAOYSA-N 2-(1-quinolin-2-ylpiperidin-4-yl)ethanol Chemical compound C1CC(CCO)CCN1C1=CC=C(C=CC=C2)C2=N1 XCWSQWUAQCIMKH-UHFFFAOYSA-N 0.000 description 2
- RDYGZWFGLGCSQJ-UHFFFAOYSA-N 2-(4-fluoro-1-quinolin-2-ylpiperidin-4-yl)ethanol Chemical compound C1CC(CCO)(F)CCN1C1=CC=C(C=CC=C2)C2=N1 RDYGZWFGLGCSQJ-UHFFFAOYSA-N 0.000 description 2
- MBPUXARSVLMTGQ-UHFFFAOYSA-N 2-(4-naphthalen-1-ylpiperazin-1-yl)ethanamine Chemical compound C1CN(CCN)CCN1C1=CC=CC2=CC=CC=C12 MBPUXARSVLMTGQ-UHFFFAOYSA-N 0.000 description 2
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-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
- IYTGRZLVQBOFEE-UHFFFAOYSA-N 2-[1-(5-chloroquinolin-2-yl)piperidin-4-yl]ethanol Chemical compound C1CC(CCO)CCN1C1=CC=C(C(Cl)=CC=C2)C2=N1 IYTGRZLVQBOFEE-UHFFFAOYSA-N 0.000 description 2
- LNCCCCKMUOVQQL-UHFFFAOYSA-N 2-[1-(6-bromopyridin-2-yl)piperidin-4-yl]ethanol Chemical compound C1CC(CCO)CCN1C1=CC=CC(Br)=N1 LNCCCCKMUOVQQL-UHFFFAOYSA-N 0.000 description 2
- QOQJCCRENPEWOP-UHFFFAOYSA-N 2-[1-(6-chloroquinolin-2-yl)piperidin-4-yl]ethanol Chemical compound C1CC(CCO)CCN1C1=CC=C(C=C(Cl)C=C2)C2=N1 QOQJCCRENPEWOP-UHFFFAOYSA-N 0.000 description 2
- IYFZWDNAENACAO-UHFFFAOYSA-N 2-[1-(6-fluoroisoquinolin-1-yl)piperidin-4-yl]ethanol Chemical compound C1CC(CCO)CCN1C1=NC=CC2=CC(F)=CC=C12 IYFZWDNAENACAO-UHFFFAOYSA-N 0.000 description 2
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| PCT/FR2004/001102 WO2004099176A1 (fr) | 2003-05-07 | 2004-05-06 | Derives de piperidinyl- et piperazinyl-alkylcarbamates, leurs procedes de preparation et leur application en therapeutique |
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| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| EP2937341B1 (en) | 2004-12-30 | 2017-07-05 | Janssen Pharmaceutica N.V. | 4-(benzyl)-piperazine-1-carboxylic acid phenylamide derivatives and related compounds as modulators of fatty acid amide hydrolase (faah) for the treatment of anxiety, pain and other conditions |
| FR2885364B1 (fr) * | 2005-05-03 | 2007-06-29 | Sanofi Aventis Sa | Derives d'alkyl-, alkenyl-et alkynylcarbamates, leur preparation et leur application en therapeutique |
| US7541359B2 (en) | 2005-06-30 | 2009-06-02 | Janssen Pharmaceutica N.V. | N-heteroarylpiperazinyl ureas as modulators of fatty acid amide hydrolase |
| WO2008030752A2 (en) * | 2006-09-07 | 2008-03-13 | N.V. Organon | Methods for determining effective doses of fatty acid amide hydrolase inhibitors in vivo |
| EP1903037A1 (de) * | 2006-09-07 | 2008-03-26 | Bayer Schering Pharma Aktiengesellschaft | 1-(Het)aryl-3-[hetaryl-piperidin-4-yl]-thioharnstoffe als Modulatoren des EP2-Rezeptors |
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| TWI434842B (zh) * | 2008-07-14 | 2014-04-21 | Astellas Pharma Inc | Azole compounds |
| FR2934265B1 (fr) * | 2008-07-23 | 2010-07-30 | Sanofi Aventis | Derives de carbamates d'alkylthiazoles, leur preparation et leur application en therapeutique |
| FR2938537B1 (fr) * | 2008-11-14 | 2012-10-26 | Sanofi Aventis | Derives de carbamates d'alkyl-heterocycles, leur preparation et leur application en therapeutique. |
| FR2941696B1 (fr) * | 2009-02-05 | 2011-04-15 | Sanofi Aventis | Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| EP2421848A1 (en) * | 2009-04-22 | 2012-02-29 | Janssen Pharmaceutica N.V. | Azetidinyl diamides as monoacylglycerol lipase inhibitors |
| 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 |
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| WO2011085216A2 (en) | 2010-01-08 | 2011-07-14 | Ironwood Pharmaceuticals, Inc. | Use of faah inhibitors for treating parkinson's disease and restless legs syndrome |
| US20130224151A1 (en) | 2010-03-31 | 2013-08-29 | United States Of America | Use of FAAH Inhibitors for Treating Abdominal, Visceral and Pelvic Pain |
| UA108233C2 (uk) | 2010-05-03 | 2015-04-10 | Модулятори активності гідролази амідів жирних кислот | |
| GB201017345D0 (en) | 2010-10-14 | 2010-11-24 | Proximagen Ltd | Receptor antagonists |
| MX350788B (es) * | 2012-01-06 | 2017-09-13 | Abide Therapeutics Inc | Compuestos de carbamato y preparación y uso de los mismos. |
| DE102012018115A1 (de) | 2012-09-13 | 2014-03-13 | Matthias Lehr | Aryl-N-(arylalkyl)carbamate als Hemmstoffe der Fatty Acid Amide Hydrolase |
| EP3022179B1 (en) | 2013-07-18 | 2017-11-15 | Fondazione Istituto Italiano Di Tecnologia | Phenyl carbamates and their use as inhibitors of the fatty acid amide hydrolase (faah) enzyme and modulators of the d3 dopamine receptor (d3dr) |
| 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 |
| JP6927882B2 (ja) | 2015-04-02 | 2021-09-01 | プロキシマジェン,リミティド ライアビリティ カンパニー | 癌の新治療法 |
| JP2023550153A (ja) * | 2020-11-23 | 2023-11-30 | エフ. ホフマン-ラ ロシュ アーゲー | B型肝炎ウイルス感染症の処置および予防のためのn-[(1,3-ベンゾオキサゾル-2-イル)-複素環]アミド誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3235565A1 (de) * | 1982-09-25 | 1984-03-29 | Boehringer Ingelheim KG, 6507 Ingelheim | Piperidinderivate, ihre herstellung und verwendung |
| FR2761266B1 (fr) * | 1997-03-28 | 1999-07-02 | Sanofi Sa | Composition pharmaceutique formee par granulation humide pour l'administration orale d'un derive du n-piperidino-3- pyrazolecarboxamide, de ses sels et de leurs solvates |
| FR2783246B1 (fr) * | 1998-09-11 | 2000-11-17 | Aventis Pharma Sa | Derives d'azetidine, leur preparation et les medicaments les contenant |
| FR2805818B1 (fr) * | 2000-03-03 | 2002-04-26 | Aventis Pharma Sa | Derives d'azetidine, leur preparation et les compositions pharmaceutiques les contenant |
| FR2816938B1 (fr) | 2000-11-22 | 2003-01-03 | Sanofi Synthelabo | Derives de 3-aroylindole, leur procede de preparation et les compositions pharmaceutiques en contenant |
| FR2843964B1 (fr) * | 2002-08-29 | 2004-10-01 | Sanofi Synthelabo | Derives de dioxane-2-alkylcarbamates, leur preparation et leur application en therapeutique |
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