DK2710013T3 - New compounds such as diacylglycerol-acyltransferase inhibitors - Google Patents

Info

Publication number

DK2710013T3

DK2710013T3 DK12789931.8T DK12789931T DK2710013T3 DK 2710013 T3 DK2710013 T3 DK 2710013T3 DK 12789931 T DK12789931 T DK 12789931T DK 2710013 T3 DK2710013 T3 DK 2710013T3

Authority

DK

Denmark

Prior art keywords

amino

pyrimido

oxazepine

indol

alkyl

Prior art date

2011-05-20

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims description 230
• 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 title description 3
• 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 title description 3
• 239000002404 acyltransferase inhibitor Substances 0.000 title 1
• -1 dihydroinda-zolyl Chemical group 0.000 claims description 87
• 150000003839 salts Chemical class 0.000 claims description 61
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 31
• 150000001408 amides Chemical class 0.000 claims description 28
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 125000004043 oxo group Chemical group O=* 0.000 claims description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
• 150000002431 hydrogen Chemical class 0.000 claims description 14
• 208000008589 Obesity Diseases 0.000 claims description 13
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
• 125000004104 aryloxy group Chemical group 0.000 claims description 13
• 235000020824 obesity Nutrition 0.000 claims description 13
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 229910052757 nitrogen Inorganic materials 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
• 125000001041 indolyl group Chemical group 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 5
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000006516 2-(benzyloxy)ethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• GIJZWPYKNBZTRK-UHFFFAOYSA-N 2-[6-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)-1-oxo-3,4-dihydroisoquinolin-2-yl]acetic acid Chemical compound O=C1C=2C(N)=NC=NC=2OCCN1C1=CC=C(C(=O)N(CC(O)=O)CC2)C2=C1 GIJZWPYKNBZTRK-UHFFFAOYSA-N 0.000 claims description 2
• UKGRUOALCSMHAM-UHFFFAOYSA-N 4-amino-6-(3-oxo-1-propan-2-yl-2h-indazol-5-yl)-7,8-dihydro-6h-oxepino[2,3-d]pyrimidin-5-one Chemical compound C1COC2=NC=NC(N)=C2C(=O)C1C1=CC=C2N(C(C)C)NC(=O)C2=C1 UKGRUOALCSMHAM-UHFFFAOYSA-N 0.000 claims description 2
• MKYVVLNIZHWCMY-UHFFFAOYSA-N 4-amino-6-[1-(2-methoxyethyl)-3-oxo-2h-indazol-5-yl]-7,8-dihydro-6h-oxepino[2,3-d]pyrimidin-5-one Chemical compound C1COC2=NC=NC(N)=C2C(=O)C1C1=CC=C2N(CCOC)NC(=O)C2=C1 MKYVVLNIZHWCMY-UHFFFAOYSA-N 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• IOLIDZWFJXMGRJ-UHFFFAOYSA-N 6-amino-4-(1-propylbenzimidazol-5-yl)-2,3-dihydro-1,4-benzoxazepin-5-one Chemical compound C1COC2=CC=CC(N)=C2C(=O)N1C1=CC=C2N(CCC)C=NC2=C1 IOLIDZWFJXMGRJ-UHFFFAOYSA-N 0.000 claims description 2
• NBJDSMIOWPVWRW-UHFFFAOYSA-N 2h-oxazepin-5-one Chemical compound O=C1C=CNOC=C1 NBJDSMIOWPVWRW-UHFFFAOYSA-N 0.000 claims 40
• 229910052736 halogen Inorganic materials 0.000 claims 13
• 150000002367 halogens Chemical class 0.000 claims 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 12
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 3
• WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 claims 3
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 3
• VZJJHNNFKSSGBO-UHFFFAOYSA-N 6,7-dihydro-2h-oxazepin-5-one Chemical compound O=C1CCONC=C1 VZJJHNNFKSSGBO-UHFFFAOYSA-N 0.000 claims 3
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 2
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
• REVKWYWODJDFMM-UHFFFAOYSA-N 3-[5-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)indol-1-yl]propanoic acid Chemical compound O=C1C=2C(N)=NC=NC=2OCCN1C1=CC=C(N(CCC(O)=O)C=C2)C2=C1 REVKWYWODJDFMM-UHFFFAOYSA-N 0.000 claims 1
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 claims 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 462
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 194
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 139
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 131
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
• 239000000243 solution Substances 0.000 description 126
• 239000012044 organic layer Substances 0.000 description 106
• 239000007787 solid Substances 0.000 description 105
• 229910001868 water Inorganic materials 0.000 description 103
• 239000012267 brine Substances 0.000 description 100
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 100
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 99
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 98
• 229910052938 sodium sulfate Inorganic materials 0.000 description 98
• 235000011152 sodium sulphate Nutrition 0.000 description 98
• 229920006395 saturated elastomer Polymers 0.000 description 96
• 238000005160 1H NMR spectroscopy Methods 0.000 description 94
• 239000000047 product Substances 0.000 description 94
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 92
• 239000000203 mixture Substances 0.000 description 89
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 80
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 67
• 238000006243 chemical reaction Methods 0.000 description 58
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 56
• 238000003818 flash chromatography Methods 0.000 description 54
• 235000002639 sodium chloride Nutrition 0.000 description 54
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 50
• 239000003921 oil Substances 0.000 description 49
• 239000000543 intermediate Substances 0.000 description 48
• 235000019198 oils Nutrition 0.000 description 48
• 239000011541 reaction mixture Substances 0.000 description 44
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
• 238000000034 method Methods 0.000 description 39
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 37
• 239000000706 filtrate Substances 0.000 description 35
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 35
• 239000003153 chemical reaction reagent Substances 0.000 description 33
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
• 229910000024 caesium carbonate Inorganic materials 0.000 description 32
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• 229910021529 ammonia Inorganic materials 0.000 description 21
• 125000005843 halogen group Chemical group 0.000 description 21
• 229910000027 potassium carbonate Inorganic materials 0.000 description 21
• 239000010949 copper Substances 0.000 description 19
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 19
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 19
• 229910052786 argon Inorganic materials 0.000 description 16
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 16
• 238000000746 purification Methods 0.000 description 16
• RXNNHSKCCHGJQM-UHFFFAOYSA-N 4,6-dichloropyrimidine-5-carbonyl chloride Chemical compound ClC(=O)C1=C(Cl)N=CN=C1Cl RXNNHSKCCHGJQM-UHFFFAOYSA-N 0.000 description 15
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 239000003480 eluent Substances 0.000 description 15
• 235000017557 sodium bicarbonate Nutrition 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 14
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 229910052802 copper Inorganic materials 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• 239000003814 drug Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• XDXFUMZONWWODJ-UHFFFAOYSA-N 2-[tert-butyl(dimethyl)silyl]oxyethanamine Chemical compound CC(C)(C)[Si](C)(C)OCCN XDXFUMZONWWODJ-UHFFFAOYSA-N 0.000 description 12
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 239000006188 syrup Substances 0.000 description 12
• 235000020357 syrup Nutrition 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 10
• 125000004122 cyclic group Chemical group 0.000 description 10
• 238000006467 substitution reaction Methods 0.000 description 10
• 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 10
• 235000015320 potassium carbonate Nutrition 0.000 description 9
• 239000002002 slurry Substances 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Substances [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 7
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 7
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 7
• 102000004190 Enzymes Human genes 0.000 description 7
• 108090000790 Enzymes Proteins 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 125000000623 heterocyclic group Chemical group 0.000 description 6
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 6
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 6
• 125000003367 polycyclic group Chemical group 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 239000012453 solvate Substances 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
• 101000927974 Homo sapiens Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 5
• 125000002252 acyl group Chemical group 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
• 125000001246 bromo group Chemical group Br* 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 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 5
• 238000005828 desilylation reaction Methods 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 238000006798 ring closing metathesis reaction Methods 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 5
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