ES2590929T3 - Derivados de bencilsulfonamida útiles como inhibidores de MOGAT-2 - Google Patents
Derivados de bencilsulfonamida útiles como inhibidores de MOGAT-2 Download PDFInfo
- Publication number
- ES2590929T3 ES2590929T3 ES13703234.8T ES13703234T ES2590929T3 ES 2590929 T3 ES2590929 T3 ES 2590929T3 ES 13703234 T ES13703234 T ES 13703234T ES 2590929 T3 ES2590929 T3 ES 2590929T3
- Authority
- ES
- Spain
- Prior art keywords
- mmol
- compound according
- mixture
- ch2och3
- add
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 3
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical class NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 22
- -1 -CH2OCH3 Chemical group 0.000 claims abstract description 16
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims abstract description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 8
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
- APVUSRACSWCXNU-HKUYNNGSSA-N n-[(1s)-1-[4-[[[(2s)-3-ethoxy-2-(5-fluoropyridin-2-yl)oxypropyl]amino]methyl]phenyl]-2,2,2-trifluoroethyl]methanesulfonamide Chemical compound C([C@@H](COCC)OC=1N=CC(F)=CC=1)NCC1=CC=C([C@H](NS(C)(=O)=O)C(F)(F)F)C=C1 APVUSRACSWCXNU-HKUYNNGSSA-N 0.000 claims description 3
- 229910016523 CuKa Inorganic materials 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- CELKOWQJPVJKIL-UHFFFAOYSA-N 3-fluoropyridine Chemical compound FC1=CC=CN=C1 CELKOWQJPVJKIL-UHFFFAOYSA-N 0.000 claims 1
- 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 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 33
- 238000003756 stirring Methods 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 239000012141 concentrate Substances 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- TUXBGZFXTLRCBT-QMMMGPOBSA-N (2s)-2-(5-fluoropyridin-2-yl)oxy-3-methoxypropan-1-amine Chemical compound COC[C@H](CN)OC1=CC=C(F)C=N1 TUXBGZFXTLRCBT-QMMMGPOBSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- KOAXAFRYJKDXEP-VIFPVBQESA-N n-[(1s)-2,2,2-trifluoro-1-(4-formylphenyl)ethyl]methanesulfonamide Chemical compound CS(=O)(=O)N[C@H](C(F)(F)F)C1=CC=C(C=O)C=C1 KOAXAFRYJKDXEP-VIFPVBQESA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- KCUPVXOSUHCIJO-UHFFFAOYSA-N 1-(4-fluorophenoxy)-3-methoxypropan-2-amine Chemical compound COCC(N)COC1=CC=C(F)C=C1 KCUPVXOSUHCIJO-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- CGWDABYOHPEOAD-UHFFFAOYSA-N 2-[(4-fluorophenoxy)methyl]oxirane Chemical compound C1=CC(F)=CC=C1OCC1OC1 CGWDABYOHPEOAD-UHFFFAOYSA-N 0.000 description 3
- XARVANDLQOZMMJ-CHHVJCJISA-N 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-oxo-2-(2-oxoethylamino)ethylidene]amino]oxy-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)O\N=C(/C(=O)NCC=O)C1=CSC(N)=N1 XARVANDLQOZMMJ-CHHVJCJISA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 150000001414 amino alcohols Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- ZUFCCCNTJRQNCF-ZETCQYMHSA-N (1s)-1-(4-bromophenyl)-2,2,2-trifluoroethanamine Chemical compound FC(F)(F)[C@@H](N)C1=CC=C(Br)C=C1 ZUFCCCNTJRQNCF-ZETCQYMHSA-N 0.000 description 2
- IDSWHVZEQHESIJ-BYPYZUCNSA-N (2s)-1-amino-3-methoxypropan-2-ol Chemical compound COC[C@@H](O)CN IDSWHVZEQHESIJ-BYPYZUCNSA-N 0.000 description 2
- LGMNCCOYXJNRAB-UHFFFAOYSA-N 1-(4-fluorophenoxy)-3-methoxypropan-2-ol Chemical compound COCC(O)COC1=CC=C(F)C=C1 LGMNCCOYXJNRAB-UHFFFAOYSA-N 0.000 description 2
- QXLNOXPJDNEXIJ-UHFFFAOYSA-N 1-(4-fluorophenoxy)-3-methoxypropan-2-one Chemical compound COCC(=O)COC1=CC=C(F)C=C1 QXLNOXPJDNEXIJ-UHFFFAOYSA-N 0.000 description 2
- BGCVOBFBVRPZJO-UHFFFAOYSA-N 1-ethoxy-3-(4-fluorophenoxy)propan-2-ol Chemical compound CCOCC(O)COC1=CC=C(F)C=C1 BGCVOBFBVRPZJO-UHFFFAOYSA-N 0.000 description 2
- HNVCVHUTWAXKJU-UHFFFAOYSA-N 2-(4-fluorophenoxy)propane-1,3-diol Chemical compound OCC(CO)OC1=CC=C(F)C=C1 HNVCVHUTWAXKJU-UHFFFAOYSA-N 0.000 description 2
- KPUMCTWECQORQQ-UHFFFAOYSA-N 3-ethoxy-2-(5-fluoropyridin-2-yl)oxypropan-1-amine Chemical compound CCOCC(CN)OC1=CC=C(F)C=N1 KPUMCTWECQORQQ-UHFFFAOYSA-N 0.000 description 2
- VCAPNZPYMIJETM-UHFFFAOYSA-N 3-ethoxy-n,n-bis[(4-methoxyphenyl)methyl]-2-pyridin-2-yloxypropan-1-amine Chemical compound C=1C=CC=NC=1OC(COCC)CN(CC=1C=CC(OC)=CC=1)CC1=CC=C(OC)C=C1 VCAPNZPYMIJETM-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000012425 OXONE® Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- PFOBABFKUMRJTE-UHFFFAOYSA-N [1-ethoxy-3-(4-fluorophenoxy)propan-2-yl] methanesulfonate Chemical compound CCOCC(OS(C)(=O)=O)COC1=CC=C(F)C=C1 PFOBABFKUMRJTE-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000013367 dietary fats Nutrition 0.000 description 2
- WKYHKYRYDDSPPE-UHFFFAOYSA-N diethyl 2-(4-fluorophenoxy)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)OC1=CC=C(F)C=C1 WKYHKYRYDDSPPE-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- VBKJAUSXTKHUMT-SSDOTTSWSA-N n-[(1r)-1-(4-bromophenyl)ethyl]methanesulfonamide Chemical compound CS(=O)(=O)N[C@H](C)C1=CC=C(Br)C=C1 VBKJAUSXTKHUMT-SSDOTTSWSA-N 0.000 description 2
- YUXQSZNZGIKWCP-APBUJDDRSA-N n-[(1s)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@H](C(F)(F)F)C1=CC=C(Br)C=C1 YUXQSZNZGIKWCP-APBUJDDRSA-N 0.000 description 2
- OAUUELNLQZYHKI-QMMMGPOBSA-N n-[(1s)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]methanesulfonamide Chemical compound CS(=O)(=O)N[C@H](C(F)(F)F)C1=CC=C(Br)C=C1 OAUUELNLQZYHKI-QMMMGPOBSA-N 0.000 description 2
- HJKYXKSLRZKNSI-UHFFFAOYSA-I pentapotassium;hydrogen sulfate;oxido sulfate;sulfuric acid Chemical compound [K+].[K+].[K+].[K+].[K+].OS([O-])(=O)=O.[O-]S([O-])(=O)=O.OS(=O)(=O)O[O-].OS(=O)(=O)O[O-] HJKYXKSLRZKNSI-UHFFFAOYSA-I 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- SOZMSEPDYJGBEK-ZCFIWIBFSA-N (1r)-1-(4-bromophenyl)ethanamine Chemical compound C[C@@H](N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-ZCFIWIBFSA-N 0.000 description 1
- HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 description 1
- PCXPPKOCUWQETF-RXMQYKEDSA-N (2r)-1-amino-3-ethoxypropan-2-ol Chemical compound CCOC[C@H](O)CN PCXPPKOCUWQETF-RXMQYKEDSA-N 0.000 description 1
- TUXBGZFXTLRCBT-MRVPVSSYSA-N (2r)-2-(5-fluoropyridin-2-yl)oxy-3-methoxypropan-1-amine Chemical compound COC[C@@H](CN)OC1=CC=C(F)C=N1 TUXBGZFXTLRCBT-MRVPVSSYSA-N 0.000 description 1
- CGMFSXWWICXGTN-SSDOTTSWSA-N (2r)-2-pyridin-2-yloxypropan-1-amine Chemical compound NC[C@@H](C)OC1=CC=CC=N1 CGMFSXWWICXGTN-SSDOTTSWSA-N 0.000 description 1
- LYGNMSMUTCMNQF-SSDOTTSWSA-N (2r)-2-pyridin-3-yloxypropan-1-amine Chemical compound NC[C@@H](C)OC1=CC=CN=C1 LYGNMSMUTCMNQF-SSDOTTSWSA-N 0.000 description 1
- RCLJNSBDDUITDV-QMMMGPOBSA-N (2s)-3-methoxy-2-pyridin-2-yloxypropan-1-amine Chemical compound COC[C@H](CN)OC1=CC=CC=N1 RCLJNSBDDUITDV-QMMMGPOBSA-N 0.000 description 1
- LDRVYZUIUHRGAW-JEMSNHSXSA-N (nz)-n-[(4-bromophenyl)methylidene]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)\N=C/C1=CC=C(Br)C=C1 LDRVYZUIUHRGAW-JEMSNHSXSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- PCXPPKOCUWQETF-UHFFFAOYSA-N 1-amino-3-ethoxypropan-2-ol Chemical compound CCOCC(O)CN PCXPPKOCUWQETF-UHFFFAOYSA-N 0.000 description 1
- KBILPVXURLWXLN-UHFFFAOYSA-N 1-ethoxy-3-(4-fluorophenoxy)propan-2-amine Chemical compound CCOCC(N)COC1=CC=C(F)C=C1 KBILPVXURLWXLN-UHFFFAOYSA-N 0.000 description 1
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
- 102000004277 11-beta-hydroxysteroid dehydrogenases Human genes 0.000 description 1
- 108090000874 11-beta-hydroxysteroid dehydrogenases Proteins 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- XFAMUOYNXFXQTC-UHFFFAOYSA-N 2,5-difluoropyridine Chemical compound FC1=CC=C(F)N=C1 XFAMUOYNXFXQTC-UHFFFAOYSA-N 0.000 description 1
- INIITJYOOWWWNT-UHFFFAOYSA-N 2-(4-fluorophenoxy)-3-methoxypropan-1-ol Chemical compound COCC(CO)OC1=CC=C(F)C=C1 INIITJYOOWWWNT-UHFFFAOYSA-N 0.000 description 1
- VTQGEXCRGJRXET-UHFFFAOYSA-N 2-(5-fluoropyridin-2-yl)oxyethanamine Chemical compound NCCOC1=CC=C(F)C=N1 VTQGEXCRGJRXET-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
- NESZFKGHRGZHAD-UHFFFAOYSA-N 2-pyridin-2-yloxybutan-1-amine Chemical compound CCC(CN)OC1=CC=CC=N1 NESZFKGHRGZHAD-UHFFFAOYSA-N 0.000 description 1
- XOEZYEUEXJHXPS-UHFFFAOYSA-N 3-(4-fluorophenoxy)-2-methoxypropan-1-amine Chemical compound COC(CN)COC1=CC=C(F)C=C1 XOEZYEUEXJHXPS-UHFFFAOYSA-N 0.000 description 1
- QBDKFJOWRMSQPX-UHFFFAOYSA-N 3-ethoxy-2-(5-fluoropyridin-2-yl)oxy-n,n-bis[(4-methoxyphenyl)methyl]propan-1-amine Chemical compound C=1C=C(F)C=NC=1OC(COCC)CN(CC=1C=CC(OC)=CC=1)CC1=CC=C(OC)C=C1 QBDKFJOWRMSQPX-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 101000785259 Crocosmia x crocosmiiflora Myricetin 3-O-glucosyl 1,2-rhamnoside 6'-O-caffeoyltransferase AT2 Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 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 1
- 241000124008 Mammalia Species 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- MFTALSJBGCQGLO-UHFFFAOYSA-N [2-(4-fluorophenoxy)-3-methoxypropyl] methanesulfonate Chemical compound CS(=O)(=O)OCC(COC)OC1=CC=C(F)C=C1 MFTALSJBGCQGLO-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- FNJVDWXUKLTFFL-UHFFFAOYSA-N diethyl 2-bromopropanedioate Chemical compound CCOC(=O)C(Br)C(=O)OCC FNJVDWXUKLTFFL-UHFFFAOYSA-N 0.000 description 1
- 239000012972 dimethylethanolamine Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- BQBYSLAFGRVJME-UHFFFAOYSA-L molybdenum(2+);dichloride Chemical compound Cl[Mo]Cl BQBYSLAFGRVJME-UHFFFAOYSA-L 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- NZANNRRPTURUBK-MRVPVSSYSA-N n-[(1r)-1-(4-formylphenyl)ethyl]methanesulfonamide Chemical compound CS(=O)(=O)N[C@H](C)C1=CC=C(C=O)C=C1 NZANNRRPTURUBK-MRVPVSSYSA-N 0.000 description 1
- WABAQGXACLHBLA-GHMZBOCLSA-N n-[(1r)-1-[4-[[[(2r)-2-hydroxypropyl]amino]methyl]phenyl]ethyl]methanesulfonamide Chemical compound C[C@@H](O)CNCC1=CC=C([C@@H](C)NS(C)(=O)=O)C=C1 WABAQGXACLHBLA-GHMZBOCLSA-N 0.000 description 1
- AIRWKEBUNMIGHA-SKDRFNHKSA-N n-[(1s)-2,2,2-trifluoro-1-[4-[[[(2r)-2-hydroxypropyl]amino]methyl]phenyl]ethyl]methanesulfonamide Chemical compound C[C@@H](O)CNCC1=CC=C([C@H](NS(C)(=O)=O)C(F)(F)F)C=C1 AIRWKEBUNMIGHA-SKDRFNHKSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000003203 triacylglycerol group Chemical group 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
-
- 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261592717P | 2012-01-31 | 2012-01-31 | |
| US201261592717P | 2012-01-31 | ||
| EP12382432 | 2012-11-06 | ||
| EP12382432 | 2012-11-06 | ||
| PCT/US2013/022870 WO2013116075A1 (en) | 2012-01-31 | 2013-01-24 | Benzyl sulfonamide derivatives useful as mogat - 2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2590929T3 true ES2590929T3 (es) | 2016-11-24 |
Family
ID=47148691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13703234.8T Active ES2590929T3 (es) | 2012-01-31 | 2013-01-24 | Derivados de bencilsulfonamida útiles como inhibidores de MOGAT-2 |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US8575352B2 (enExample) |
| EP (1) | EP2809651B1 (enExample) |
| JP (1) | JP2015511232A (enExample) |
| KR (1) | KR20140106750A (enExample) |
| CN (1) | CN104066719B (enExample) |
| AP (1) | AP2014007794A0 (enExample) |
| AR (1) | AR089771A1 (enExample) |
| AU (1) | AU2013215468A1 (enExample) |
| BR (1) | BR112014018636A8 (enExample) |
| CA (1) | CA2859995A1 (enExample) |
| CL (1) | CL2014001861A1 (enExample) |
| CO (1) | CO7010839A2 (enExample) |
| CR (1) | CR20140322A (enExample) |
| DO (1) | DOP2014000178A (enExample) |
| EA (1) | EA201491276A1 (enExample) |
| ES (1) | ES2590929T3 (enExample) |
| GT (1) | GT201400167A (enExample) |
| HK (1) | HK1199025A1 (enExample) |
| IL (1) | IL233712A0 (enExample) |
| MA (1) | MA35886B1 (enExample) |
| MX (1) | MX2014008599A (enExample) |
| PE (1) | PE20141679A1 (enExample) |
| PH (1) | PH12014501711A1 (enExample) |
| SG (1) | SG11201404106QA (enExample) |
| TW (1) | TW201343629A (enExample) |
| WO (1) | WO2013116075A1 (enExample) |
| ZA (1) | ZA201404836B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9073856B2 (en) | 2012-01-23 | 2015-07-07 | Eli Lilly And Company | Phenyl methanesulfonamide derivatives useful as MGAT-2 inhibitors |
| BR112014018712A8 (pt) | 2012-01-31 | 2017-07-11 | Lilly Co Eli | Derivados de morfolinila úteis como inibidores de mogat-2 |
| US9416138B2 (en) | 2012-11-06 | 2016-08-16 | Eli Lilly And Company | Benzyl sulfonamide compounds useful as MoGAT-2 inhibitors |
| MX389242B (es) | 2015-06-15 | 2025-03-20 | Nmd Pharma As | Compuestos para su uso en el tratamiento de trastornos neuromusculares |
| TWI782056B (zh) | 2017-07-14 | 2022-11-01 | 日商鹽野義製藥股份有限公司 | 具有ｍｇａｔ２抑制活性的縮合環衍生物 |
| US10385028B2 (en) | 2017-12-14 | 2019-08-20 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US11730714B2 (en) | 2017-12-14 | 2023-08-22 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US11591284B2 (en) | 2017-12-14 | 2023-02-28 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US11147788B2 (en) | 2017-12-14 | 2021-10-19 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| US12440477B2 (en) | 2017-12-14 | 2025-10-14 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| MX2021008050A (es) | 2019-01-11 | 2021-08-05 | Shionogi & Co | Derivado de dihidropirazolopirazinona que tiene actividad inhibidora de monoacilglicerol aciltransferasa 2 (mgat2). |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1659113A1 (en) * | 2004-11-08 | 2006-05-24 | Evotec AG | Inhibitors of 11beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) |
| EP1655283A1 (en) | 2004-11-08 | 2006-05-10 | Evotec OAI AG | 11beta-HSD1 Inhibitors |
| CN101087771A (zh) * | 2004-11-10 | 2007-12-12 | 辉瑞大药厂 | 经取代n－磺酰基氨基苄基－2－苯氧基乙酰胺化合物 |
| AU2005303492A1 (en) * | 2004-11-10 | 2006-05-18 | Pfizer Inc. | Substituted N-sulfonylaminobenzyl-2-phenoxy acetamide compounds |
| CN101511808A (zh) * | 2006-09-08 | 2009-08-19 | 辉瑞产品公司 | 二芳基醚衍生物及其用途 |
| EP2078719A4 (en) | 2006-09-28 | 2009-11-11 | Dainippon Sumitomo Pharma Co | COMPOUND WITH BICYCLIC PYRIMIDINE STRUCTURE AND THE COMPOUND CONTAINING PHARMACEUTICAL COMPOSITION |
| CN101583593A (zh) * | 2006-11-13 | 2009-11-18 | 辉瑞产品公司 | 二芳基、二吡啶基和芳基-吡啶基衍生物及其用途 |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| AU2010216633A1 (en) | 2009-02-23 | 2011-09-08 | Msd K.K. | Pyrimidin-4(3H)-one derivatives |
| US9073856B2 (en) | 2012-01-23 | 2015-07-07 | Eli Lilly And Company | Phenyl methanesulfonamide derivatives useful as MGAT-2 inhibitors |
| BR112014018712A8 (pt) | 2012-01-31 | 2017-07-11 | Lilly Co Eli | Derivados de morfolinila úteis como inibidores de mogat-2 |
-
2013
- 2013-01-21 AR ARP130100180A patent/AR089771A1/es unknown
- 2013-01-21 TW TW102102260A patent/TW201343629A/zh unknown
- 2013-01-24 AU AU2013215468A patent/AU2013215468A1/en not_active Abandoned
- 2013-01-24 MX MX2014008599A patent/MX2014008599A/es unknown
- 2013-01-24 KR KR1020147021127A patent/KR20140106750A/ko not_active Ceased
- 2013-01-24 EA EA201491276A patent/EA201491276A1/ru unknown
- 2013-01-24 BR BR112014018636A patent/BR112014018636A8/pt not_active IP Right Cessation
- 2013-01-24 SG SG11201404106QA patent/SG11201404106QA/en unknown
- 2013-01-24 US US13/748,627 patent/US8575352B2/en not_active Expired - Fee Related
- 2013-01-24 HK HK14112466.4A patent/HK1199025A1/xx unknown
- 2013-01-24 WO PCT/US2013/022870 patent/WO2013116075A1/en not_active Ceased
- 2013-01-24 PE PE2014001197A patent/PE20141679A1/es not_active Application Discontinuation
- 2013-01-24 CN CN201380007085.XA patent/CN104066719B/zh active Active
- 2013-01-24 JP JP2014555589A patent/JP2015511232A/ja not_active Ceased
- 2013-01-24 EP EP13703234.8A patent/EP2809651B1/en active Active
- 2013-01-24 ES ES13703234.8T patent/ES2590929T3/es active Active
- 2013-01-24 CA CA2859995A patent/CA2859995A1/en not_active Abandoned
- 2013-01-24 AP AP2014007794A patent/AP2014007794A0/xx unknown
-
2014
- 2014-06-30 ZA ZA2014/04836A patent/ZA201404836B/en unknown
- 2014-07-04 CR CR20140322A patent/CR20140322A/es unknown
- 2014-07-15 CL CL2014001861A patent/CL2014001861A1/es unknown
- 2014-07-17 IL IL233712A patent/IL233712A0/en unknown
- 2014-07-24 MA MA37244A patent/MA35886B1/fr unknown
- 2014-07-24 CO CO14161422A patent/CO7010839A2/es unknown
- 2014-07-29 GT GT201400167A patent/GT201400167A/es unknown
- 2014-07-30 PH PH12014501711A patent/PH12014501711A1/en unknown
- 2014-07-30 DO DO2014000178A patent/DOP2014000178A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PE20141679A1 (es) | 2014-11-08 |
| US8575352B2 (en) | 2013-11-05 |
| SG11201404106QA (en) | 2014-08-28 |
| CN104066719B (zh) | 2016-08-24 |
| AU2013215468A1 (en) | 2014-07-10 |
| JP2015511232A (ja) | 2015-04-16 |
| KR20140106750A (ko) | 2014-09-03 |
| IL233712A0 (en) | 2014-09-30 |
| CN104066719A (zh) | 2014-09-24 |
| AP2014007794A0 (en) | 2014-07-31 |
| DOP2014000178A (es) | 2014-08-31 |
| CL2014001861A1 (es) | 2014-11-07 |
| TW201343629A (zh) | 2013-11-01 |
| EA201491276A1 (ru) | 2014-10-30 |
| HK1199025A1 (en) | 2015-06-19 |
| CA2859995A1 (en) | 2013-08-08 |
| US20130197039A1 (en) | 2013-08-01 |
| WO2013116075A1 (en) | 2013-08-08 |
| CO7010839A2 (es) | 2014-07-31 |
| MX2014008599A (es) | 2014-08-22 |
| MA35886B1 (fr) | 2014-12-01 |
| ZA201404836B (en) | 2017-08-30 |
| EP2809651A1 (en) | 2014-12-10 |
| PH12014501711A1 (en) | 2014-10-13 |
| EP2809651B1 (en) | 2016-06-29 |
| AR089771A1 (es) | 2014-09-17 |
| GT201400167A (es) | 2015-05-28 |
| CR20140322A (es) | 2014-08-25 |
| BR112014018636A2 (enExample) | 2017-06-20 |
| BR112014018636A8 (pt) | 2017-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2590929T3 (es) | Derivados de bencilsulfonamida útiles como inhibidores de MOGAT-2 | |
| ES2878160T3 (es) | Derivados de 5,7-dihidro-pirrolo-piridina para el tratamiento de enfermedades neurológicas y neurodegenerativas | |
| CA3087912C (en) | Prodrugs of ketamine, compositions and uses thereof | |
| KR102659213B1 (ko) | Jak1 선택적 억제제 | |
| JP7263266B2 (ja) | ジヒドロ－ピロロ－ピリジン誘導体 | |
| JP2013514356A (ja) | ピロロ［２，３−ｄ］ピリミジン化合物 | |
| ES2779225T3 (es) | Reactivos de merilformilo sustituido y procedimiento de uso de los mismos para modificar propiedades fisicoquímicas y/o farmacocinéticas de compuestos | |
| IL288174B1 (en) | Pyrrolidine compounds | |
| JP7497294B2 (ja) | ピペラジンアザスピロ誘導体 | |
| TW202045164A (zh) | 化合物、組合物及方法 | |
| ES2733502T3 (es) | Compuestos de imidazopiridazina | |
| CN108290911A (zh) | (r)-及(s)-1-(3-(3-n,n-二甲基胺基羰基)苯氧基-4-硝苯基)-1-乙基-n,n’-双(伸乙基)胺基磷酸酯、组合物及其使用及制备方法 | |
| JP2026510901A (ja) | 化学化合物 | |
| ES2377465T3 (es) | Bencilaminas, un proceso para su producción y su uso como agentes anti-inflamatorios | |
| ES2818806T3 (es) | Novedosas ciclopropabenzofuranil piridopirazindionas | |
| ES2775674T3 (es) | Compuestos de 6,7-dihidro-5H-pirazolo[5,1-b][1,3]oxazina-2-carboxamida | |
| CN117615760A (zh) | 整联蛋白抑制剂的扩大剂量方案 | |
| AU2023391870A1 (en) | Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels | |
| ES2909709T3 (es) | Inhibidores del receptor 2 activado por proteasa | |
| TWI899933B (zh) | 經取代吲唑丙酸衍生化合物及其用途 | |
| CA2901766A1 (en) | N-(2-cyano heterocyclyl)pyrazolo pyridones as janus kinase inhibitors | |
| CN115677507B (zh) | 氟比洛芬衍生物及其在药物中的应用 | |
| CA3152836A1 (en) | Substituted urea dihydroorotate dehydrogenase inhibitors | |
| JP2016501844A (ja) | ＭｏＧＡＴ−２阻害剤として有用な新規のベンジルスルホンアミド化合物 | |
| AU2024289347A1 (en) | Nmt inhibitor, and preparation method therefor and use thereof |