DE60316683T2 - Phenylcyclohexylpropanolaminderivate, deren herstellung und therapeutsche anwendung - Google Patents
Phenylcyclohexylpropanolaminderivate, deren herstellung und therapeutsche anwendung Download PDFInfo
- Publication number
- DE60316683T2 DE60316683T2 DE60316683T DE60316683T DE60316683T2 DE 60316683 T2 DE60316683 T2 DE 60316683T2 DE 60316683 T DE60316683 T DE 60316683T DE 60316683 T DE60316683 T DE 60316683T DE 60316683 T2 DE60316683 T2 DE 60316683T2
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 230000001225 therapeutic effect Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 50
- 125000005843 halogen group Chemical group 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims abstract description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 95
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
- 125000006239 protecting group Chemical group 0.000 claims description 24
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 239000012453 solvate Substances 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 150000004677 hydrates Chemical class 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 6
- 150000002118 epoxides Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 2
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 2
- 206010036600 Premature labour Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 claims description 2
- 230000003178 anti-diabetic effect Effects 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 230000008991 intestinal motility Effects 0.000 claims description 2
- 230000002366 lipolytic effect Effects 0.000 claims description 2
- 208000026440 premature labor Diseases 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000000506 psychotropic effect Effects 0.000 claims description 2
- 230000037390 scarring Effects 0.000 claims description 2
- 229940125712 tocolytic agent Drugs 0.000 claims description 2
- 239000003675 tocolytic agent Substances 0.000 claims description 2
- 230000003195 tocolytic effect Effects 0.000 claims description 2
- 230000001430 anti-depressive effect Effects 0.000 claims 1
- 229940005513 antidepressants Drugs 0.000 claims 1
- 238000002483 medication Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- -1 substituted Chemical class 0.000 abstract description 46
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 86
- 239000002904 solvent Substances 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 230000002829 reductive effect Effects 0.000 description 44
- 239000000203 mixture Substances 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 238000001704 evaporation Methods 0.000 description 33
- 230000008020 evaporation Effects 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 25
- 239000007787 solid Substances 0.000 description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 23
- 239000003480 eluent Substances 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 238000000746 purification Methods 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 0 CCC(CC*(C)CC(C)CC*)C(C)(CC(C)C)*(C*1)*CC1=* Chemical compound CCC(CC*(C)CC(C)CC*)C(C)(CC(C)C)*(C*1)*CC1=* 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- YJPRMAKYHDHWRV-YGGJGDQASA-N 4-[4-[benzyl-[(2s)-2-hydroxy-3-(3-methylsulfonyl-4-phenylmethoxyphenoxy)propyl]amino]cyclohexyl]benzoic acid Chemical compound C([C@H](O)COC=1C=C(C(=CC=1)OCC=1C=CC=CC=1)S(=O)(=O)C)N(C1CCC(CC1)C=1C=CC(=CC=1)C(O)=O)CC1=CC=CC=C1 YJPRMAKYHDHWRV-YGGJGDQASA-N 0.000 description 5
- LHQVXISTZLUQRG-YGGJGDQASA-N 4-[4-[benzyl-[(2s)-2-hydroxy-3-[3-(methanesulfonamido)-4-phenylmethoxyphenoxy]propyl]amino]cyclohexyl]benzoic acid Chemical compound C([C@H](O)COC=1C=C(C(=CC=1)OCC=1C=CC=CC=1)NS(=O)(=O)C)N(C1CCC(CC1)C=1C=CC(=CC=1)C(O)=O)CC1=CC=CC=C1 LHQVXISTZLUQRG-YGGJGDQASA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229960005190 phenylalanine Drugs 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- MGSNYAFYXNFVON-KVZIAJEVSA-N 2-[4-[4-[[(2s)-2-hydroxy-3-[4-hydroxy-3-(methanesulfonamido)phenoxy]propyl]amino]cyclohexyl]phenoxy]acetic acid Chemical compound C1=C(O)C(NS(=O)(=O)C)=CC(OC[C@@H](O)CNC2CCC(CC2)C=2C=CC(OCC(O)=O)=CC=2)=C1 MGSNYAFYXNFVON-KVZIAJEVSA-N 0.000 description 3
- GNSBLLWRROKPTQ-UHFFFAOYSA-N 4-[4-(benzylamino)cyclohexyl]phenol Chemical compound C1=CC(O)=CC=C1C1CCC(NCC=2C=CC=CC=2)CC1 GNSBLLWRROKPTQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IWINARNQIHMTMS-HCGLCNNCSA-N CCOC(=O)COc1ccc(cc1)[C@H]1CC[C@@H](CC1)N(Cc1ccccc1)C(=O)OC(C)(C)C Chemical compound CCOC(=O)COc1ccc(cc1)[C@H]1CC[C@@H](CC1)N(Cc1ccccc1)C(=O)OC(C)(C)C IWINARNQIHMTMS-HCGLCNNCSA-N 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 230000009471 action Effects 0.000 description 3
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- 239000008346 aqueous phase Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
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- 125000004185 ester group Chemical group 0.000 description 3
- 150000002148 esters Chemical group 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 150000002576 ketones Chemical group 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- WTKVDEZCRMIEGK-KVWWFHCMSA-N n-[2-hydroxy-5-[(2s)-2-hydroxy-3-[[4-(4-hydroxyphenyl)cyclohexyl]amino]propoxy]phenyl]methanesulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)C)=CC(OC[C@@H](O)CNC2CCC(CC2)C=2C=CC(O)=CC=2)=C1 WTKVDEZCRMIEGK-KVWWFHCMSA-N 0.000 description 3
- YWUPFZHXZIRMMJ-STEQJIOHSA-N n-[2-hydroxy-5-[(2s)-2-hydroxy-3-[[4-(4-phenylphenyl)cyclohexyl]amino]propoxy]phenyl]methanesulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)C)=CC(OC[C@@H](O)CNC2CCC(CC2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 YWUPFZHXZIRMMJ-STEQJIOHSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- VMKJKEINOOXOCH-GOSISDBHSA-N tert-butyl n-methylsulfonyl-n-[5-[[(2s)-oxiran-2-yl]methoxy]-2-phenylmethoxyphenyl]carbamate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(N(C(=O)OC(C)(C)C)S(C)(=O)=O)=CC=1OC[C@@H]1CO1 VMKJKEINOOXOCH-GOSISDBHSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 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 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- ZKLPQSVDCKBQCO-IGMOWHQGSA-N CS(=O)(=O)Nc1cc(OC[C@@H](O)CN(Cc2ccccc2)[C@H]2CC[C@@H](CC2)c2ccc(cc2)-c2ccccc2)ccc1OCc1ccccc1 Chemical compound CS(=O)(=O)Nc1cc(OC[C@@H](O)CN(Cc2ccccc2)[C@H]2CC[C@@H](CC2)c2ccc(cc2)-c2ccccc2)ccc1OCc1ccccc1 ZKLPQSVDCKBQCO-IGMOWHQGSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
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- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- FPFQPLFYTKMCHN-PPHPATTJSA-N ethyl (2s)-2-amino-3-phenylpropanoate;hydron;chloride Chemical compound Cl.CCOC(=O)[C@@H](N)CC1=CC=CC=C1 FPFQPLFYTKMCHN-PPHPATTJSA-N 0.000 description 1
- DHLOEIXGWMIRIJ-UHFFFAOYSA-N ethyl 2-[4-(4-aminocyclohexyl)phenoxy]-2-methylpropanoate Chemical compound C1=CC(OC(C)(C)C(=O)OCC)=CC=C1C1CCC(N)CC1 DHLOEIXGWMIRIJ-UHFFFAOYSA-N 0.000 description 1
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- 230000007170 pathology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- GRJHONXDTNBDTC-UHFFFAOYSA-N phenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC=C1 GRJHONXDTNBDTC-UHFFFAOYSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
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- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
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- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- A61P25/24—Antidepressants
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- A61P27/06—Antiglaucoma agents or miotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Pregnancy & Childbirth (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0206561 | 2002-05-29 | ||
| FR0206561A FR2840301B1 (fr) | 2002-05-29 | 2002-05-29 | Derives de phenyl-cyclohexyl-propanolamine, leur preparation et leur applicaton en therapeutique |
| PCT/FR2003/001580 WO2003099772A1 (fr) | 2002-05-29 | 2003-05-26 | Derives de phenyl-cyclohexyl-propanolamine, leur preparation et leur application en therapeutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60316683D1 DE60316683D1 (de) | 2007-11-15 |
| DE60316683T2 true DE60316683T2 (de) | 2008-07-17 |
Family
ID=29558808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60316683T Expired - Lifetime DE60316683T2 (de) | 2002-05-29 | 2003-05-26 | Phenylcyclohexylpropanolaminderivate, deren herstellung und therapeutsche anwendung |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7453010B2 (https=) |
| EP (1) | EP1511722B1 (https=) |
| JP (1) | JP4393376B2 (https=) |
| AT (1) | ATE374748T1 (https=) |
| AU (1) | AU2003263229A1 (https=) |
| DE (1) | DE60316683T2 (https=) |
| FR (1) | FR2840301B1 (https=) |
| WO (1) | WO2003099772A1 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2817257B1 (fr) * | 2000-11-30 | 2009-03-20 | Sanofi Synthelabo | Cyclohexyl(alkyl)-propanolamines, leur preparation et compositions pharmaceutiques en contenant |
| US7795283B2 (en) * | 2004-12-14 | 2010-09-14 | Astrazeneca Ab | Oxadiazole derivative as DGAT inhibitors |
| US7749997B2 (en) * | 2005-12-22 | 2010-07-06 | Astrazeneca Ab | Pyrimido [4,5-B] -Oxazines for use as DGAT inhibitors |
| WO2007138304A1 (en) | 2006-05-30 | 2007-12-06 | Astrazeneca Ab | 1, 3, 4 -oxadiazole derivatives as dgat1 inhibitors |
| JP2009538892A (ja) | 2006-05-30 | 2009-11-12 | アストラゼネカ アクチボラグ | アセチル補酵素ａジアシルグリセロールアシルトランスフェラーゼの阻害薬としての置換５−フェニルアミノ−１，３，４−オキサジアゾール−２−イルカルボニルアミノ−４−フェノキシ−シクロヘキサンカルボン酸 |
| ES2359653T3 (es) * | 2006-06-08 | 2011-05-25 | Astrazeneca Ab | Bencimidazoles y su uso para el tratamiento de la diabetes. |
| GB0611507D0 (en) * | 2006-06-10 | 2006-07-19 | Astrazeneca Ab | Chemical compounds |
| EP2011490A1 (en) * | 2007-07-05 | 2009-01-07 | Sanofi-Aventis | Beta adrenergic receptor ligand derivatives for modulating apoptosis |
| WO2009024821A2 (en) * | 2007-08-17 | 2009-02-26 | Astrazeneca Ab | Oxadiazole derivatives as dgat inhibitors |
| EP2234978B1 (en) | 2007-12-20 | 2015-02-25 | AstraZeneca AB | Carbamoyl compounds as dgat1 inhibitors 190 |
| FR2935141B1 (fr) * | 2008-08-21 | 2010-10-08 | Sanofi Aventis | Procede de preparation de l'ester ethylique de l'acide 4-[trans-4-[(phenylmethyl)-amino]cyclohexyl]benzoique et de son sel hemifumarate |
| BRPI0924669A2 (pt) * | 2008-12-19 | 2016-01-26 | Astrazeneca Ab | composto, uso de um composto, método para tratar a diabete melito e/ou obesidade, e, composição farmacêutica |
| NZ594244A (en) | 2009-01-28 | 2013-07-26 | Sanofi Sa | Thiadiazole and oxadiazole derivatives, preparation thereof, and therapeutic use thereof |
| BRPI1016109A2 (pt) | 2009-06-19 | 2016-05-17 | Astrazeneca Ab | "composto, composição farmacêutica, e, processo para preparar um composto" |
| FR2963005B1 (fr) | 2010-07-23 | 2012-08-17 | Sanofi Aventis | Derives d'oxadiazoles et de pyridazines, leur preparation et leur application en therapeutique |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4004028A (en) * | 1975-08-06 | 1977-01-18 | Smithkline Corporation | Phenoxypropanolamines |
| CN1023402C (zh) * | 1988-06-03 | 1994-01-05 | 伊莱利利公司 | 制备5-羟色胺拮抗药的方法 |
| FR2780057B1 (fr) * | 1998-06-18 | 2002-09-13 | Sanofi Sa | Phenoxypropanolamines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| FR2817257B1 (fr) * | 2000-11-30 | 2009-03-20 | Sanofi Synthelabo | Cyclohexyl(alkyl)-propanolamines, leur preparation et compositions pharmaceutiques en contenant |
-
2002
- 2002-05-29 FR FR0206561A patent/FR2840301B1/fr not_active Expired - Fee Related
-
2003
- 2003-05-26 DE DE60316683T patent/DE60316683T2/de not_active Expired - Lifetime
- 2003-05-26 AU AU2003263229A patent/AU2003263229A1/en not_active Abandoned
- 2003-05-26 JP JP2004507430A patent/JP4393376B2/ja not_active Expired - Fee Related
- 2003-05-26 WO PCT/FR2003/001580 patent/WO2003099772A1/fr not_active Ceased
- 2003-05-26 AT AT03755202T patent/ATE374748T1/de not_active IP Right Cessation
- 2003-05-26 EP EP03755202A patent/EP1511722B1/fr not_active Expired - Lifetime
- 2003-05-26 US US10/515,145 patent/US7453010B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1511722B1 (fr) | 2007-10-03 |
| FR2840301B1 (fr) | 2007-03-23 |
| JP2005530809A (ja) | 2005-10-13 |
| DE60316683D1 (de) | 2007-11-15 |
| WO2003099772A1 (fr) | 2003-12-04 |
| US20060100283A1 (en) | 2006-05-11 |
| US7453010B2 (en) | 2008-11-18 |
| JP4393376B2 (ja) | 2010-01-06 |
| AU2003263229A1 (en) | 2003-12-12 |
| ATE374748T1 (de) | 2007-10-15 |
| EP1511722A1 (fr) | 2005-03-09 |
| FR2840301A1 (fr) | 2003-12-05 |
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