CA2719650A1 - Bicyclic nitrogen-containing heterocyclic compounds for use as stearoyl coa desaturase inhibitors - Google Patents

Info

Publication number

CA2719650A1

CA2719650A1 CA2719650A CA2719650A CA2719650A1 CA 2719650 A1 CA2719650 A1 CA 2719650A1 CA 2719650 A CA2719650 A CA 2719650A CA 2719650 A CA2719650 A CA 2719650A CA 2719650 A1 CA2719650 A1 CA 2719650A1

Authority

CA

Canada

Prior art keywords

methyl

oxo

amino

ethyl

pyrazin

Prior art date

2008-04-10

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• -1 Bicyclic nitrogen-containing heterocyclic compounds Chemical class 0.000 title claims abstract description 177
• 108010087894 Fatty acid desaturases Proteins 0.000 title claims abstract description 70
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 title claims abstract 5
• 239000003112 inhibitor Substances 0.000 title abstract description 13
• 150000001875 compounds Chemical class 0.000 claims abstract description 224
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 56
• 201000010099 disease Diseases 0.000 claims abstract description 40
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 522
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 306
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 273
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 205
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 133
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
• 125000000217 alkyl group Chemical group 0.000 claims description 89
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 83
• 125000003118 aryl group Chemical group 0.000 claims description 68
• 125000001072 heteroaryl group Chemical group 0.000 claims description 67
• 125000001424 substituent group Chemical group 0.000 claims description 54
• 238000000034 method Methods 0.000 claims description 44
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 41
• 125000000623 heterocyclic group Chemical group 0.000 claims description 35
• 125000003342 alkenyl group Chemical group 0.000 claims description 26
• 239000001257 hydrogen Substances 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 23
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 125000000304 alkynyl group Chemical group 0.000 claims description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 14
• 150000003857 carboxamides Chemical class 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 12
• 239000002253 acid Substances 0.000 claims description 12
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims description 12
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 7
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
• 150000002148 esters Chemical class 0.000 claims description 7
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 230000002401 inhibitory effect Effects 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 235000019260 propionic acid Nutrition 0.000 claims description 6
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
• 239000005711 Benzoic acid Substances 0.000 claims description 5
• 235000010233 benzoic acid Nutrition 0.000 claims description 5
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 5
• 239000000651 prodrug Substances 0.000 claims description 5
• 229940002612 prodrug Drugs 0.000 claims description 5
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 4
• 101100240528 Caenorhabditis elegans nhr-23 gene Proteins 0.000 claims description 4
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
• PECASCCOCBSCNN-UHFFFAOYSA-N benzyl n-[1-(2-acetamidoethyl)-3-(4-methoxyphenyl)-2-oxoquinoxalin-6-yl]carbamate Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NC(=O)OCC=3C=CC=CC=3)=CC=C2N(CCNC(C)=O)C1=O PECASCCOCBSCNN-UHFFFAOYSA-N 0.000 claims description 4
• NDCVRWXYSAVFBF-UHFFFAOYSA-N n-[2-[7-(benzylamino)-2-methyl-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=C2N=C(C)C(=O)N(CCNC(=O)C)C2=NC=C1NCC1=CC=CC=C1 NDCVRWXYSAVFBF-UHFFFAOYSA-N 0.000 claims description 4
• HISJLSXOXJASNK-UHFFFAOYSA-N n-[2-[7-[(4-fluoro-3-methylphenyl)methylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCC1=CC=C(F)C(C)=C1 HISJLSXOXJASNK-UHFFFAOYSA-N 0.000 claims description 4
• KDRGWBDOBCLUSE-UHFFFAOYSA-N n-[2-[7-[[4-chloro-3-(trifluoromethyl)phenyl]methylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCC1=CC=C(Cl)C(C(F)(F)F)=C1 KDRGWBDOBCLUSE-UHFFFAOYSA-N 0.000 claims description 4
• NIPZZXUFJPQHNH-UHFFFAOYSA-M pyrazine-2-carboxylate Chemical compound [O-]C(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-M 0.000 claims description 4
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• VZQUYZBJYXLPLQ-CQSZACIVSA-N (2r)-2-hydroxy-n-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethyl]propanamide Chemical compound C=1C=C2N=C(C)C(=O)N(CCNC(=O)[C@H](O)C)C2=CC=1NCC1=CC=CC(C(F)(F)F)=C1 VZQUYZBJYXLPLQ-CQSZACIVSA-N 0.000 claims description 3
• VZQUYZBJYXLPLQ-AWEZNQCLSA-N (2s)-2-hydroxy-n-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethyl]propanamide Chemical compound C=1C=C2N=C(C)C(=O)N(CCNC(=O)[C@@H](O)C)C2=CC=1NCC1=CC=CC(C(F)(F)F)=C1 VZQUYZBJYXLPLQ-AWEZNQCLSA-N 0.000 claims description 3
• PRZKVPSEKMHFIS-UHFFFAOYSA-N 2,3-dihydroxy-n-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethyl]propanamide Chemical compound C1=C2N(CCNC(=O)C(O)CO)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 PRZKVPSEKMHFIS-UHFFFAOYSA-N 0.000 claims description 3
• APYONNMRNATNGB-UHFFFAOYSA-N 2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethylurea Chemical compound C1=C2N(CCNC(N)=O)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 APYONNMRNATNGB-UHFFFAOYSA-N 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
• OPWMHRPIBJVJTC-UHFFFAOYSA-N 3-hydroxy-n-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethyl]propanamide Chemical compound C1=C2N(CCNC(=O)CCO)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 OPWMHRPIBJVJTC-UHFFFAOYSA-N 0.000 claims description 3
• PNTFZUUBGCDWBF-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]propanamide Chemical compound C1=C2N(CCC(=O)NCCO)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 PNTFZUUBGCDWBF-UHFFFAOYSA-N 0.000 claims description 3
• HUYPGJIKHOQUMM-UHFFFAOYSA-N n-[2-[3-(4-methoxyphenyl)-2-oxo-7-[[4-(trifluoromethyl)pyridin-2-yl]methylamino]quinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCC1=CC(C(F)(F)F)=CC=N1 HUYPGJIKHOQUMM-UHFFFAOYSA-N 0.000 claims description 3
• LXSJTXGBHUBLGP-UHFFFAOYSA-N n-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethyl]thiophene-3-carboxamide Chemical compound C1=C2N(CCNC(=O)C3=CSC=C3)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 LXSJTXGBHUBLGP-UHFFFAOYSA-N 0.000 claims description 3
• QKGSSBJCIRWSPU-UHFFFAOYSA-N n-[2-[7-[(3,4-dichlorophenyl)methylamino]-2-(4-methoxyphenyl)-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NCC=3C=C(Cl)C(Cl)=CC=3)=CN=C2N(CCNC(C)=O)C1=O QKGSSBJCIRWSPU-UHFFFAOYSA-N 0.000 claims description 3
• ITRSXXVLXWPSCR-UHFFFAOYSA-N n-[2-[7-[(3,4-dimethylphenyl)methylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCC1=CC=C(C)C(C)=C1 ITRSXXVLXWPSCR-UHFFFAOYSA-N 0.000 claims description 3
• LWQHYXWNNUMNRP-UHFFFAOYSA-N n-[2-[7-[2-(2-chlorophenoxy)ethylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCCOC1=CC=CC=C1Cl LWQHYXWNNUMNRP-UHFFFAOYSA-N 0.000 claims description 3
• VNGUXYAVBLCMGD-UHFFFAOYSA-N n-[2-[7-[2-(3-chlorophenyl)ethylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCCC1=CC=CC(Cl)=C1 VNGUXYAVBLCMGD-UHFFFAOYSA-N 0.000 claims description 3
• HBNUDNGIQMHVDM-UHFFFAOYSA-N n-[2-[7-[2-(4-chlorophenyl)ethylamino]-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCCC1=CC=C(Cl)C=C1 HBNUDNGIQMHVDM-UHFFFAOYSA-N 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 3
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
• 239000005977 Ethylene Substances 0.000 claims description 2
• RMRDBXLTNLYWON-UHFFFAOYSA-N benzyl n-[1-(2-acetamidoethyl)-3-(3,4-dichlorophenyl)-2-oxoquinoxalin-6-yl]carbamate Chemical compound C1=C2N=C(C=3C=C(Cl)C(Cl)=CC=3)C(=O)N(CCNC(=O)C)C2=CC=C1NC(=O)OCC1=CC=CC=C1 RMRDBXLTNLYWON-UHFFFAOYSA-N 0.000 claims description 2
• RMUZJCKZFYPSDO-UHFFFAOYSA-N benzyl n-[4-(2-acetamidoethyl)-2-methyl-3-oxo-1,2-dihydropyrido[2,3-b]pyrazin-7-yl]carbamate Chemical compound C=1N=C2N(CCNC(C)=O)C(=O)C(C)NC2=CC=1NC(=O)OCC1=CC=CC=C1 RMUZJCKZFYPSDO-UHFFFAOYSA-N 0.000 claims description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 2
• QJXVUGMMRSPJTG-UHFFFAOYSA-N n-[2-[2-(3,4-dichlorophenyl)-7-[(3,4-dichlorophenyl)methylamino]-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=C2N=C(C=3C=C(Cl)C(Cl)=CC=3)C(=O)N(CCNC(=O)C)C2=NC=C1NCC1=CC=C(Cl)C(Cl)=C1 QJXVUGMMRSPJTG-UHFFFAOYSA-N 0.000 claims description 2
• PMFXOWYBXXMNDR-UHFFFAOYSA-N n-[2-[2-(4-methoxyphenyl)-3-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]pyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NCC=3C=C(C=CC=3)C(F)(F)F)=CN=C2N(CCNC(C)=O)C1=O PMFXOWYBXXMNDR-UHFFFAOYSA-N 0.000 claims description 2
• HLSLHEWIZKFZTP-UHFFFAOYSA-N n-[2-[2-(4-methoxyphenyl)-7-[(4-methoxyphenyl)methylamino]-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1CNC1=CN=C(N(CCNC(C)=O)C(=O)C(=N2)C=3C=CC(OC)=CC=3)C2=C1 HLSLHEWIZKFZTP-UHFFFAOYSA-N 0.000 claims description 2
• ZVDNSERVQXIYPJ-UHFFFAOYSA-N n-[2-[3-(4-methoxyphenyl)-7-[(3-methylphenyl)methylamino]-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(C(N(CCNC(C)=O)C1=C2)=O)=NC1=CC=C2NCC1=CC=CC(C)=C1 ZVDNSERVQXIYPJ-UHFFFAOYSA-N 0.000 claims description 2
• JRNCYLBRLNFWGF-UHFFFAOYSA-N n-[2-[7-[(3,4-dichlorophenyl)methylamino]-3-oxo-2-pyridin-3-ylpyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=C2N=C(C=3C=NC=CC=3)C(=O)N(CCNC(=O)C)C2=NC=C1NCC1=CC=C(Cl)C(Cl)=C1 JRNCYLBRLNFWGF-UHFFFAOYSA-N 0.000 claims description 2
• FWPIWLQAPAHJHW-UHFFFAOYSA-N n-[2-[7-[(3-chlorophenyl)methylamino]-2-(4-methoxyphenyl)-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NCC=3C=C(Cl)C=CC=3)=CN=C2N(CCNC(C)=O)C1=O FWPIWLQAPAHJHW-UHFFFAOYSA-N 0.000 claims description 2
• DJVYKNSSXZJQBQ-UHFFFAOYSA-N n-[2-[7-[(4-chlorophenyl)methylamino]-2-(4-methoxyphenyl)-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NCC=3C=CC(Cl)=CC=3)=CN=C2N(CCNC(C)=O)C1=O DJVYKNSSXZJQBQ-UHFFFAOYSA-N 0.000 claims description 2
• ZNWFXAUKPLNCOH-UHFFFAOYSA-N n-[2-[7-[2-(3,4-dichlorophenyl)ethylamino]-2-(4-methoxyphenyl)-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(NCCC=3C=C(Cl)C(Cl)=CC=3)=CN=C2N(CCNC(C)=O)C1=O ZNWFXAUKPLNCOH-UHFFFAOYSA-N 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• XZOWIJDBQIHMFC-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O.CCCC(N)=O XZOWIJDBQIHMFC-UHFFFAOYSA-N 0.000 claims 5
• 125000001475 halogen functional group Chemical group 0.000 claims 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• MTMGWUJFNDKEFG-UHFFFAOYSA-N 1-(2-acetamidoethyl)-n-[(3,4-dichlorophenyl)methyl]-3-(4-methoxyphenyl)-2-oxoquinoxaline-6-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(C(=O)NCC=3C=C(Cl)C(Cl)=CC=3)=CC=C2N(CCNC(C)=O)C1=O MTMGWUJFNDKEFG-UHFFFAOYSA-N 0.000 claims 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 1
• WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 claims 1
• 230000001404 mediated effect Effects 0.000 abstract description 14
• 208000008589 Obesity Diseases 0.000 abstract description 13
• 150000002632 lipids Chemical class 0.000 abstract description 13
• 235000020824 obesity Nutrition 0.000 abstract description 13
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 11
• 208000001145 Metabolic Syndrome Diseases 0.000 abstract description 9
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 9
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 6
• 102000004190 Enzymes Human genes 0.000 abstract description 5
• 108090000790 Enzymes Proteins 0.000 abstract description 5
• 206010039792 Seborrhoea Diseases 0.000 abstract description 4
• 230000037312 oily skin Effects 0.000 abstract description 4
• 230000002159 abnormal effect Effects 0.000 abstract description 3
• AFMGAVDATRJOJG-GUYCJALGSA-N (3s,5s)-3-methyl-5-[(4-phenylphenyl)methyl]pyrrolidin-2-one Chemical class N1C(=O)[C@@H](C)C[C@H]1CC1=CC=C(C=2C=CC=CC=2)C=C1 AFMGAVDATRJOJG-GUYCJALGSA-N 0.000 description 260
• 239000000203 mixture Substances 0.000 description 64
• 102100028897 Stearoyl-CoA desaturase Human genes 0.000 description 62
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 44
• 238000002360 preparation method Methods 0.000 description 44
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
• 238000006243 chemical reaction Methods 0.000 description 31
• 150000001412 amines Chemical class 0.000 description 30
• 101100513046 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) eth-1 gene Proteins 0.000 description 28
• 125000003545 alkoxy group Chemical group 0.000 description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 229910052736 halogen Inorganic materials 0.000 description 23
• 150000002367 halogens Chemical class 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• 229910001868 water Inorganic materials 0.000 description 23
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
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