JP2011516546A - ステアロイル−ＣｏＡデサチュラーゼのインヒビターとして使用するための二環式窒素含有複素環化合物 - Google Patents

Info

Publication number

JP2011516546A

JP2011516546A JP2011503949A JP2011503949A JP2011516546A JP 2011516546 A JP2011516546 A JP 2011516546A JP 2011503949 A JP2011503949 A JP 2011503949A JP 2011503949 A JP2011503949 A JP 2011503949A JP 2011516546 A JP2011516546 A JP 2011516546A

Authority

JP

Japan

Prior art keywords

methyl

amino

oxo

ethyl

hydropyridino

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.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Bicyclic nitrogen-containing heterocyclic compounds Chemical class 0.000 title claims abstract description 227
• 108010087894 Fatty acid desaturases Proteins 0.000 title claims abstract description 65
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 title claims abstract 5
• 239000003112 inhibitor Substances 0.000 title abstract description 15
• 150000001875 compounds Chemical class 0.000 claims abstract description 232
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 57
• 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 228
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 166
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 165
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 143
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 130
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 105
• 125000000217 alkyl group Chemical group 0.000 claims description 83
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 77
• 125000003118 aryl group Chemical group 0.000 claims description 69
• 125000001072 heteroaryl group Chemical group 0.000 claims description 62
• 125000001424 substituent group Chemical group 0.000 claims description 61
• 238000000034 method Methods 0.000 claims description 45
• 125000000623 heterocyclic group Chemical group 0.000 claims description 36
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 125000003342 alkenyl group Chemical group 0.000 claims description 26
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 24
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 23
• 229910052739 hydrogen Inorganic materials 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 150000003839 salts Chemical class 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 19
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims description 13
• 239000002253 acid Substances 0.000 claims description 13
• LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims description 12
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 11
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 11
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 150000002148 esters Chemical class 0.000 claims description 7
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 6
• PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 claims description 6
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 6
• 150000001408 amides Chemical class 0.000 claims description 6
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
• 230000002401 inhibitory effect Effects 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
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 239000000651 prodrug Substances 0.000 claims description 5
• 229940002612 prodrug Drugs 0.000 claims description 5
• 235000019260 propionic acid Nutrition 0.000 claims description 5
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 5
• AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims description 4
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 4
• 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 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
• 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
• APYONNMRNATNGB-UHFFFAOYSA-N 2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethylurea Chemical group 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
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=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
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000005711 Benzoic acid Substances 0.000 claims description 3
• 101100240528 Caenorhabditis elegans nhr-23 gene Proteins 0.000 claims description 3
• 235000010233 benzoic acid Nutrition 0.000 claims description 3
• 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 3
• 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 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical group CCOC(=O)CC FKRCODPIKNYEAC-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
• 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 3
• 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 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
• 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
• 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 description 2
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 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
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[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
• JWSWKNZAKWPCIZ-UHFFFAOYSA-N C(C)(=O)NN1CC=NC=C1 Chemical compound C(C)(=O)NN1CC=NC=C1 JWSWKNZAKWPCIZ-UHFFFAOYSA-N 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
• 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
• 229940095102 methyl benzoate Drugs 0.000 claims description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 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
• 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
• 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 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
• RSIPQHOWTCNEBI-UHFFFAOYSA-N n-hydroxypropanamide Chemical compound CCC(=O)NO RSIPQHOWTCNEBI-UHFFFAOYSA-N 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 5
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 5
• 230000001404 mediated effect Effects 0.000 abstract description 15
• 150000002632 lipids Chemical class 0.000 abstract description 14
• 208000024891 symptom Diseases 0.000 abstract description 14
• 208000008589 Obesity Diseases 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 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 10
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 9
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 5
• 102000004190 Enzymes Human genes 0.000 abstract description 4
• 108090000790 Enzymes Proteins 0.000 abstract description 4
• 206010039792 Seborrhoea Diseases 0.000 abstract description 4
• 230000002159 abnormal effect Effects 0.000 abstract description 4
• 230000037312 oily skin Effects 0.000 abstract description 4
• WYKYKTKDBLFHCY-UHFFFAOYSA-N chloridazon Chemical class O=C1C(Cl)=C(N)C=NN1C1=CC=CC=C1 WYKYKTKDBLFHCY-UHFFFAOYSA-N 0.000 abstract description 2
• FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical class C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 abstract description 2
• 239000000203 mixture Substances 0.000 description 61
• 102100028897 Stearoyl-CoA desaturase Human genes 0.000 description 60
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 238000002360 preparation method Methods 0.000 description 43
• 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 25
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 229910052736 halogen Inorganic materials 0.000 description 23
• 150000002367 halogens Chemical class 0.000 description 23
• 239000000243 solution Substances 0.000 description 23
• 125000004093 cyano group Chemical group *C#N 0.000 description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
• 125000004181 carboxyalkyl group Chemical group 0.000 description 21
• 230000000694 effects Effects 0.000 description 20
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 20
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• 235000014113 dietary fatty acids Nutrition 0.000 description 18
• 229930195729 fatty acid Natural products 0.000 description 18
• 239000000194 fatty acid Substances 0.000 description 18
• 239000000047 product Substances 0.000 description 18
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 17
• 125000004432 carbon atom Chemical group C* 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 17
• 208000035475 disorder Diseases 0.000 description 17
• 150000004665 fatty acids Chemical class 0.000 description 17
• 239000007787 solid Substances 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• 239000004480 active ingredient Substances 0.000 description 16
• 238000009472 formulation Methods 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• 239000011541 reaction mixture Substances 0.000 description 14
• 210000001519 tissue Anatomy 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 238000003556 assay Methods 0.000 description 12
• 230000015572 biosynthetic process Effects 0.000 description 12
• 239000007788 liquid Substances 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
• 241001465754 Metazoa Species 0.000 description 11
• 239000012071 phase Substances 0.000 description 11
• 208000032928 Dyslipidaemia Diseases 0.000 description 10
• 208000017170 Lipid metabolism disease Diseases 0.000 description 10
• 125000004414 alkyl thio group Chemical group 0.000 description 10
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
• 239000003995 emulsifying agent Substances 0.000 description 10
• 210000004185 liver Anatomy 0.000 description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 239000003883 ointment base Substances 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 9
• 229930194542 Keto Natural products 0.000 description 9
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 125000002252 acyl group Chemical group 0.000 description 9
• 125000004442 acylamino group Chemical group 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 125000005110 aryl thio group Chemical group 0.000 description 9
• 125000004104 aryloxy group Chemical group 0.000 description 9
• 239000006071 cream Substances 0.000 description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 239000006210 lotion Substances 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• 229920001223 polyethylene glycol Polymers 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• 150000003573 thiols Chemical class 0.000 description 9
• 241000699670 Mus sp. Species 0.000 description 8
• 206010028980 Neoplasm Diseases 0.000 description 8
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 8
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
• 150000001540 azides Chemical class 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 239000000839 emulsion Substances 0.000 description 8
• 125000005368 heteroarylthio group Chemical group 0.000 description 8
• 125000004470 heterocyclooxy group Chemical group 0.000 description 8
• 125000004468 heterocyclylthio group Chemical group 0.000 description 8
• TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 8
• 210000001589 microsome Anatomy 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 150000003626 triacylglycerols Chemical class 0.000 description 8
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 239000004264 Petrolatum Substances 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 239000000499 gel Substances 0.000 description 7
• 125000005843 halogen group Chemical group 0.000 description 7
• 150000002430 hydrocarbons Chemical group 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 229940066842 petrolatum Drugs 0.000 description 7
• 235000019271 petrolatum Nutrition 0.000 description 7
• 239000004094 surface-active agent Substances 0.000 description 7
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 6
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• 108010062497 VLDL Lipoproteins Proteins 0.000 description 6
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 239000000969 carrier Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• FSFFJEWAYWRLFT-UHFFFAOYSA-N ethyl 2-(4-methoxyphenyl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CC=C(OC)C=C1 FSFFJEWAYWRLFT-UHFFFAOYSA-N 0.000 description 6
• 208000010706 fatty liver disease Diseases 0.000 description 6
• 235000011187 glycerol Nutrition 0.000 description 6
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 6
• 208000006575 hypertriglyceridemia Diseases 0.000 description 6
• 230000004048 modification Effects 0.000 description 6
• 238000012986 modification Methods 0.000 description 6
• DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical compound CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000006228 supernatant Substances 0.000 description 6
• 239000012049 topical pharmaceutical composition Substances 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• 0 *c1c[n](*)nc1 Chemical compound *c1c[n](*)nc1 0.000 description 5
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 5
• FOHHWGVAOVDVLP-UHFFFAOYSA-N 4-chloro-3-nitroaniline Chemical compound NC1=CC=C(Cl)C([N+]([O-])=O)=C1 FOHHWGVAOVDVLP-UHFFFAOYSA-N 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 108010029485 Protein Isoforms Proteins 0.000 description 5
• 102000001708 Protein Isoforms Human genes 0.000 description 5
• 125000000033 alkoxyamino group Chemical group 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• 239000012131 assay buffer Substances 0.000 description 5
• 239000007957 coemulsifier Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 239000008103 glucose Substances 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 239000004530 micro-emulsion Substances 0.000 description 5
• 239000002674 ointment Substances 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 229930195734 saturated hydrocarbon Natural products 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 229940124597 therapeutic agent Drugs 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 4
• IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 4
• SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
• 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 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• 206010019708 Hepatic steatosis Diseases 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 101100041816 Homo sapiens SCD gene Proteins 0.000 description 4
• 206010022489 Insulin Resistance Diseases 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
• 229910000564 Raney nickel Inorganic materials 0.000 description 4
• 101150097713 SCD1 gene Proteins 0.000 description 4
• 102100033930 Stearoyl-CoA desaturase 5 Human genes 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 150000003857 carboxamides Chemical class 0.000 description 4
• 235000012000 cholesterol Nutrition 0.000 description 4
• XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000003974 emollient agent Substances 0.000 description 4
• 235000019439 ethyl acetate Nutrition 0.000 description 4
• 239000003925 fat Substances 0.000 description 4
• 239000012467 final product Substances 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 230000000302 ischemic effect Effects 0.000 description 4
• ODKTZKDHTNEJBA-UHFFFAOYSA-N n-[2-(2-amino-4-bromoanilino)ethyl]acetamide Chemical compound CC(=O)NCCNC1=CC=C(Br)C=C1N ODKTZKDHTNEJBA-UHFFFAOYSA-N 0.000 description 4
• SDFGOCPNFDTVQV-UHFFFAOYSA-N n-[2-(5-bromo-2-nitroanilino)ethyl]acetamide Chemical compound CC(=O)NCCNC1=CC(Br)=CC=C1[N+]([O-])=O SDFGOCPNFDTVQV-UHFFFAOYSA-N 0.000 description 4
• BSNIYABGKKFOHO-UHFFFAOYSA-N n-[2-[[6-[(3,4-dichlorophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(Cl)C(Cl)=CC=2)=C1 BSNIYABGKKFOHO-UHFFFAOYSA-N 0.000 description 4
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 239000008188 pellet Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• SIARJEKBADXQJG-LFZQUHGESA-N stearoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SIARJEKBADXQJG-LFZQUHGESA-N 0.000 description 4
• 125000003107 substituted aryl group Chemical group 0.000 description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 239000011593 sulfur Substances 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 4
• 239000000080 wetting agent Substances 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• MJJXLLKSVSDLJO-UHFFFAOYSA-N 1-(2-aminoethyl)-3-methyl-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-2-one Chemical compound C1=C2N(CCN)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 MJJXLLKSVSDLJO-UHFFFAOYSA-N 0.000 description 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 101000639987 Homo sapiens Stearoyl-CoA desaturase 5 Proteins 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 208000017442 Retinal disease Diseases 0.000 description 3
• 206010038923 Retinopathy Diseases 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• SRHQOQMNBVOXCF-UHFFFAOYSA-N [4-chloro-3-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(Cl)C(C(F)(F)F)=C1 SRHQOQMNBVOXCF-UHFFFAOYSA-N 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 239000000010 aprotic solvent Substances 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 150000001720 carbohydrates Chemical class 0.000 description 3
• 235000014633 carbohydrates Nutrition 0.000 description 3
• 239000004359 castor oil Substances 0.000 description 3
• 235000019438 castor oil Nutrition 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• 229960000541 cetyl alcohol Drugs 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000007812 deficiency Effects 0.000 description 3
• 235000005911 diet Nutrition 0.000 description 3
• 230000037213 diet Effects 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 229940014259 gelatin Drugs 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 239000003349 gelling agent Substances 0.000 description 3
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
• 230000002440 hepatic effect Effects 0.000 description 3
• 208000006454 hepatitis Diseases 0.000 description 3
• 231100000283 hepatitis Toxicity 0.000 description 3
• 125000004475 heteroaralkyl group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 230000037356 lipid metabolism Effects 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 210000001853 liver microsome Anatomy 0.000 description 3
• 229920000609 methyl cellulose Polymers 0.000 description 3
• 239000001923 methylcellulose Substances 0.000 description 3
• 230000003228 microsomal effect Effects 0.000 description 3
• AKPHSSZZWXMRPW-UHFFFAOYSA-N n-[2-(2-amino-5-bromoanilino)ethyl]acetamide Chemical compound CC(=O)NCCNC1=CC(Br)=CC=C1N AKPHSSZZWXMRPW-UHFFFAOYSA-N 0.000 description 3
• HCKDKBVHEJGOIP-UHFFFAOYSA-N n-[2-[7-bromo-2-(4-methoxyphenyl)-3-oxopyrido[2,3-b]pyrazin-4-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(Br)=CN=C2N(CCNC(C)=O)C1=O HCKDKBVHEJGOIP-UHFFFAOYSA-N 0.000 description 3
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
• BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 3
• 150000002828 nitro derivatives Chemical class 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000011084 recovery Methods 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 231100000240 steatosis hepatitis Toxicity 0.000 description 3
• WQYUWVJITIFDFM-UHFFFAOYSA-N tert-butyl n-[2-[(6-chloro-3-nitropyridin-2-yl)amino]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNC1=NC(Cl)=CC=C1[N+]([O-])=O WQYUWVJITIFDFM-UHFFFAOYSA-N 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
• VQCWSOYHHXXWSP-UHFFFAOYSA-N 4-bromo-2-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1F VQCWSOYHHXXWSP-UHFFFAOYSA-N 0.000 description 2
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 229940123980 Desaturase inhibitor Drugs 0.000 description 2
• 208000002249 Diabetes Complications Diseases 0.000 description 2
• 206010012655 Diabetic complications Diseases 0.000 description 2
• 208000004930 Fatty Liver Diseases 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 description 2
• 201000001431 Hyperuricemia Diseases 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 208000032382 Ischaemic stroke Diseases 0.000 description 2
• 239000004166 Lanolin Substances 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 206010027525 Microalbuminuria Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 208000021642 Muscular disease Diseases 0.000 description 2
• 201000009623 Myopathy Diseases 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• 208000018262 Peripheral vascular disease Diseases 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 2
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000012317 TBTU Substances 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• 239000004164 Wax ester Substances 0.000 description 2
• 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 2
• 238000010521 absorption reaction Methods 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 229960004050 aminobenzoic acid Drugs 0.000 description 2
• 239000002280 amphoteric surfactant Substances 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 229940121375 antifungal agent Drugs 0.000 description 2
• 239000003429 antifungal agent Substances 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 229940003587 aquaphor Drugs 0.000 description 2
• 125000000732 arylene group Chemical group 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 208000026106 cerebrovascular disease Diseases 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 208000037765 diseases and disorders Diseases 0.000 description 2
• 239000002612 dispersion medium Substances 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• 125000004185 ester group Chemical group 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 150000002191 fatty alcohols Chemical class 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 229940075507 glyceryl monostearate Drugs 0.000 description 2
• HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 208000019622 heart disease Diseases 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 210000003494 hepatocyte Anatomy 0.000 description 2
• 125000005549 heteroarylene group Chemical group 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• 238000000265 homogenisation Methods 0.000 description 2
• 239000011539 homogenization buffer Substances 0.000 description 2
• 150000004678 hydrides Chemical class 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
• 201000008980 hyperinsulinism Diseases 0.000 description 2
• 208000020346 hyperlipoproteinemia Diseases 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 239000011261 inert gas Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 235000015110 jellies Nutrition 0.000 description 2
• 239000008274 jelly Substances 0.000 description 2
• 235000019388 lanolin Nutrition 0.000 description 2
• 229940039717 lanolin Drugs 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• 229960003511 macrogol Drugs 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 235000021281 monounsaturated fatty acids Nutrition 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• PMUZQRCVKWDZDI-UHFFFAOYSA-N n-[2-(4-bromo-2-nitroanilino)ethyl]acetamide Chemical compound CC(=O)NCCNC1=CC=C(Br)C=C1[N+]([O-])=O PMUZQRCVKWDZDI-UHFFFAOYSA-N 0.000 description 2
• SUAYEXXINLPLRA-UHFFFAOYSA-N n-[2-[(3-amino-5-bromopyridin-2-yl)amino]ethyl]acetamide Chemical compound CC(=O)NCCNC1=NC=C(Br)C=C1N SUAYEXXINLPLRA-UHFFFAOYSA-N 0.000 description 2
• XLOSZNLNXZRBMH-UHFFFAOYSA-N n-[2-[7-bromo-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=C(Br)C=C2N(CCNC(C)=O)C1=O XLOSZNLNXZRBMH-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 2
• 239000002736 nonionic surfactant Substances 0.000 description 2
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 230000010412 perfusion Effects 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
• BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 2
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 2
• 229940113116 polyethylene glycol 1000 Drugs 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 238000011533 pre-incubation Methods 0.000 description 2
• 201000009104 prediabetes syndrome Diseases 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• BNHGKKNINBGEQL-UHFFFAOYSA-M sodium;5-ethyl-5-(3-methylbutyl)pyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CC(C)CCC1(CC)C(=O)NC(=O)[N-]C1=O BNHGKKNINBGEQL-UHFFFAOYSA-M 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 125000005156 substituted alkylene group Chemical group 0.000 description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 150000003457 sulfones Chemical class 0.000 description 2
• 150000003462 sulfoxides Chemical class 0.000 description 2
• 230000000475 sunscreen effect Effects 0.000 description 2
• 239000000516 sunscreening agent Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 201000005665 thrombophilia Diseases 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 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
• 230000001052 transient effect Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
• 238000001291 vacuum drying Methods 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 235000019386 wax ester Nutrition 0.000 description 2
• MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical class C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical group C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
• YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical group C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical group C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
• RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• XGXKZNXCORZWLV-UHFFFAOYSA-N 1h-pyrido[3,4-b]pyrazin-2-one Chemical class N1=CC=C2NC(=O)C=NC2=C1 XGXKZNXCORZWLV-UHFFFAOYSA-N 0.000 description 1
• ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical compound C1NC=CO1 ZABMHLDQFJHDSC-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
• QUIMTLZDMCNYGY-UHFFFAOYSA-N 2,4-dichloro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1Cl QUIMTLZDMCNYGY-UHFFFAOYSA-N 0.000 description 1
• RZVJQUMDJUUBBF-UHFFFAOYSA-N 2,4-dichloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C=C1Cl RZVJQUMDJUUBBF-UHFFFAOYSA-N 0.000 description 1
• FECOOTOWJXGHGV-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=CC=C(Cl)C(Cl)=C1 FECOOTOWJXGHGV-UHFFFAOYSA-N 0.000 description 1
• IDTFANFXLFNLMC-UHFFFAOYSA-M 2-(4-methoxyphenyl)-2-oxoacetate Chemical compound COC1=CC=C(C(=O)C([O-])=O)C=C1 IDTFANFXLFNLMC-UHFFFAOYSA-M 0.000 description 1
• 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 1
• PHEOEEUQMSOOID-UHFFFAOYSA-N 2-[[3-nitro-6-[[3-(trifluoromethyl)phenyl]methylamino]pyridin-2-yl]amino]ethanol Chemical compound C1=C([N+]([O-])=O)C(NCCO)=NC(NCC=2C=C(C=CC=2)C(F)(F)F)=C1 PHEOEEUQMSOOID-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• TYYHDKOVFSVWON-UHFFFAOYSA-N 2-butyl-2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(CCCC)C(=O)C1=CC=CC=C1 TYYHDKOVFSVWON-UHFFFAOYSA-N 0.000 description 1
• VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical group C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 1
• VWJJGUYODGCWEN-UHFFFAOYSA-N 3-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]propanoic acid Chemical compound C1=C2N(CCC(O)=O)C(=O)C(C)=NC2=CC=C1NCC1=CC=CC(C(F)(F)F)=C1 VWJJGUYODGCWEN-UHFFFAOYSA-N 0.000 description 1
• FTLBMVYTGMBSKV-UHFFFAOYSA-N 3-[[6-[(3,4-dichlorophenyl)methylamino]-3-nitropyridin-2-yl]amino]propanoic acid Chemical compound C1=C([N+]([O-])=O)C(NCCC(=O)O)=NC(NCC=2C=C(Cl)C(Cl)=CC=2)=C1 FTLBMVYTGMBSKV-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical class NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• UQEANKGXXSENNF-UHFFFAOYSA-N 4-bromo-1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1F UQEANKGXXSENNF-UHFFFAOYSA-N 0.000 description 1
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
• WWQQPSDIIVXFOX-UHFFFAOYSA-N 5-bromo-2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC(Br)=CN=C1Cl WWQQPSDIIVXFOX-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000002874 Acne Vulgaris Diseases 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 102100034542 Acyl-CoA (8-3)-desaturase Human genes 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 108010071619 Apolipoproteins Proteins 0.000 description 1
• 102000007592 Apolipoproteins Human genes 0.000 description 1
• 102000013918 Apolipoproteins E Human genes 0.000 description 1
• 108010025628 Apolipoproteins E Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• ZMNIRDPLUAZRQW-UHFFFAOYSA-N COc(cc1)ccc1C1=Nc2ccc(NCc(cc3Cl)ccc3Cl)nc2N(CCN)C1=O Chemical compound COc(cc1)ccc1C1=Nc2ccc(NCc(cc3Cl)ccc3Cl)nc2N(CCN)C1=O ZMNIRDPLUAZRQW-UHFFFAOYSA-N 0.000 description 1
• 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 description 1
• 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 description 1
• 102100027943 Carnitine O-palmitoyltransferase 1, liver isoform Human genes 0.000 description 1
• 101710120614 Carnitine O-palmitoyltransferase 1, liver isoform Proteins 0.000 description 1
• 101710108984 Carnitine O-palmitoyltransferase 1, muscle isoform Proteins 0.000 description 1
• 201000002929 Carnitine palmitoyltransferase II deficiency Diseases 0.000 description 1
• 206010050215 Carnitine palmitoyltransferase deficiency Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
• 108010073542 Delta-5 Fatty Acid Desaturase Proteins 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 206010072268 Drug-induced liver injury Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 206010014486 Elevated triglycerides Diseases 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 102000015303 Fatty Acid Synthases Human genes 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 208000002705 Glucose Intolerance Diseases 0.000 description 1
• 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
• DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 206010019668 Hepatic fibrosis Diseases 0.000 description 1
• 208000033981 Hereditary haemochromatosis Diseases 0.000 description 1
• 101100309604 Homo sapiens SCD5 gene Proteins 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• 208000001021 Hyperlipoproteinemia Type I 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
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 206010065973 Iron Overload Diseases 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• 108010044467 Isoenzymes Proteins 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• 108010007622 LDL Lipoproteins Proteins 0.000 description 1
• 102000007330 LDL Lipoproteins Human genes 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 102000016267 Leptin Human genes 0.000 description 1
• 108010092277 Leptin Proteins 0.000 description 1
• 108010037138 Linoleoyl-CoA Desaturase Proteins 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 235000009421 Myristica fragrans Nutrition 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 208000001280 Prediabetic State Diseases 0.000 description 1
• 206010036618 Premenstrual syndrome Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• DZNOEQZJHXMIGD-UHFFFAOYSA-N S(=O)(=O)(O)O.OC(C(=O)O)CCCCCCCCCCCCCCCC Chemical compound S(=O)(=O)(O)O.OC(C(=O)O)CCCCCCCCCCCCCCCC DZNOEQZJHXMIGD-UHFFFAOYSA-N 0.000 description 1
• 101100101423 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UBI4 gene Proteins 0.000 description 1
• 101150042597 Scd2 gene Proteins 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000026062 Tissue disease Diseases 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• XTAPYTIXHHJGET-UHFFFAOYSA-N [2-acetyloxy-3-[2-[3-methyl-2-oxo-7-[[3-(trifluoromethyl)phenyl]methylamino]quinoxalin-1-yl]ethylamino]-3-oxopropyl] acetate Chemical compound C=1C=C2N=C(C)C(=O)N(CCNC(=O)C(OC(C)=O)COC(=O)C)C2=CC=1NCC1=CC=CC(C(F)(F)F)=C1 XTAPYTIXHHJGET-UHFFFAOYSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 206010000496 acne Diseases 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 210000001789 adipocyte Anatomy 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 229940031955 anhydrous lanolin Drugs 0.000 description 1
• 239000003945 anionic surfactant Substances 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 239000012752 auxiliary agent Substances 0.000 description 1
• 229960005193 avobenzone Drugs 0.000 description 1
• OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
• 239000012965 benzophenone Substances 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• SMXGADWNKGMRKB-UHFFFAOYSA-N benzyl n-(4-chloro-3-nitrophenyl)carbamate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(NC(=O)OCC=2C=CC=CC=2)=C1 SMXGADWNKGMRKB-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 229960001714 calcium phosphate Drugs 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• 229960003340 calcium silicate Drugs 0.000 description 1
• 235000012241 calcium silicate Nutrition 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 229960001631 carbomer Drugs 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000003093 cationic surfactant Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 229940114081 cinnamate Drugs 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 108010086283 delta-9 fatty acid desaturase Proteins 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 1
• 150000004985 diamines Chemical class 0.000 description 1
• 125000005266 diarylamine group Chemical group 0.000 description 1
• NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical compound C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 201000008865 drug-induced hepatitis Diseases 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 201000008220 erythropoietic protoporphyria Diseases 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical class CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 230000004129 fatty acid metabolism Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 235000021588 free fatty acids Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 230000004190 glucose uptake Effects 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 150000002314 glycerols Chemical class 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 125000005241 heteroarylamino group Chemical group 0.000 description 1
• 235000009200 high fat diet Nutrition 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229960002885 histidine Drugs 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical group C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000003983 inhalation anesthetic agent Substances 0.000 description 1
• 239000010954 inorganic particle Substances 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
• 229940039781 leptin Drugs 0.000 description 1
• 230000006372 lipid accumulation Effects 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 208000016332 liver symptom Diseases 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 235000004213 low-fat Nutrition 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 239000001115 mace Substances 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 235000013622 meat product Nutrition 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 208000011661 metabolic syndrome X Diseases 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• UVOBWHVLRGZKTK-UHFFFAOYSA-N n-[2-(7-bromo-2-methyl-3-oxopyrido[2,3-b]pyrazin-4-yl)ethyl]acetamide Chemical compound C1=C(Br)C=C2N=C(C)C(=O)N(CCNC(=O)C)C2=N1 UVOBWHVLRGZKTK-UHFFFAOYSA-N 0.000 description 1
• WRLNHUNXJLOGPP-UHFFFAOYSA-N n-[2-[(5-bromo-3-nitropyridin-2-yl)amino]ethyl]acetamide Chemical compound CC(=O)NCCNC1=NC=C(Br)C=C1[N+]([O-])=O WRLNHUNXJLOGPP-UHFFFAOYSA-N 0.000 description 1
• XKHMATHIHDUTJK-UHFFFAOYSA-N n-[2-[6-bromo-3-(4-methoxyphenyl)-2-oxoquinoxalin-1-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC(Br)=CC=C2N(CCNC(C)=O)C1=O XKHMATHIHDUTJK-UHFFFAOYSA-N 0.000 description 1
• VJVAHDYURPXIDK-UHFFFAOYSA-N n-[2-[[3-nitro-6-[[3-(trifluoromethyl)phenyl]methylamino]pyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(C=CC=2)C(F)(F)F)=C1 VJVAHDYURPXIDK-UHFFFAOYSA-N 0.000 description 1
• UZSVEWANBDXHFM-UHFFFAOYSA-N n-[2-[[3-nitro-6-[[4-(trifluoromethyl)phenyl]methylamino]pyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=CC(=CC=2)C(F)(F)F)=C1 UZSVEWANBDXHFM-UHFFFAOYSA-N 0.000 description 1
• GNGWLQWPALGVGW-UHFFFAOYSA-N n-[2-[[3-nitro-6-[[5-(trifluoromethyl)pyridin-3-yl]methylamino]pyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(C=NC=2)C(F)(F)F)=C1 GNGWLQWPALGVGW-UHFFFAOYSA-N 0.000 description 1
• BZVQOSYVMLKXQY-UHFFFAOYSA-N n-[2-[[3-nitro-6-[[6-(trifluoromethyl)pyridin-2-yl]methylamino]pyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2N=C(C=CC=2)C(F)(F)F)=C1 BZVQOSYVMLKXQY-UHFFFAOYSA-N 0.000 description 1
• TVBVBKDXFYNVLI-UHFFFAOYSA-N n-[2-[[6-[(3-bromophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(Br)C=CC=2)=C1 TVBVBKDXFYNVLI-UHFFFAOYSA-N 0.000 description 1
• ZPLRTPNVWGJUMI-UHFFFAOYSA-N n-[2-[[6-[(3-chloro-4-fluorophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(Cl)C(F)=CC=2)=C1 ZPLRTPNVWGJUMI-UHFFFAOYSA-N 0.000 description 1
• OGYDQHBMDBYDGX-UHFFFAOYSA-N n-[2-[[6-[(3-chlorophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(Cl)C=CC=2)=C1 OGYDQHBMDBYDGX-UHFFFAOYSA-N 0.000 description 1
• HATKXNCAEPSWMM-UHFFFAOYSA-N n-[2-[[6-[(4-fluorophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=CC(F)=CC=2)=C1 HATKXNCAEPSWMM-UHFFFAOYSA-N 0.000 description 1
• WYPSJPZTVOELHH-UHFFFAOYSA-N n-[2-[[6-[[3,5-bis(trifluoromethyl)phenyl]methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=C1 WYPSJPZTVOELHH-UHFFFAOYSA-N 0.000 description 1
• DGEZCQQRARYGOG-UHFFFAOYSA-N n-[2-[[6-[[4-fluoro-3-(trifluoromethyl)phenyl]methylamino]-3-nitropyridin-2-yl]amino]ethyl]acetamide Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)C)=NC(NCC=2C=C(C(F)=CC=2)C(F)(F)F)=C1 DGEZCQQRARYGOG-UHFFFAOYSA-N 0.000 description 1
• GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
• HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
• 235000021590 normal diet Nutrition 0.000 description 1
• 235000003715 nutritional status Nutrition 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
• 229960001679 octinoxate Drugs 0.000 description 1
• 229960003921 octisalate Drugs 0.000 description 1
• WCJLCOAEJIHPCW-UHFFFAOYSA-N octyl 2-hydroxybenzoate Chemical compound CCCCCCCCOC(=O)C1=CC=CC=C1O WCJLCOAEJIHPCW-UHFFFAOYSA-N 0.000 description 1
• 230000009965 odorless effect Effects 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
• 229960001173 oxybenzone Drugs 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920000223 polyglycerol Polymers 0.000 description 1
• 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• MBHCWRKFAXKMRT-UHFFFAOYSA-N propanoic acid;1-tetradecoxytetradecane Chemical compound CCC(O)=O.CCCCCCCCCCCCCCOCCCCCCCCCCCCCC MBHCWRKFAXKMRT-UHFFFAOYSA-N 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 208000020016 psychiatric disease Diseases 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000004141 reverse cholesterol transport Effects 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 150000003902 salicylic acid esters Chemical class 0.000 description 1
• 150000004671 saturated fatty acids Chemical group 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 229920002545 silicone oil Polymers 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000007863 steatosis Effects 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 229920002994 synthetic fiber Polymers 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
• IOWVNWZRIQAUAD-UHFFFAOYSA-N tert-butyl n-[2-(2-amino-5-bromoanilino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNC1=CC(Br)=CC=C1N IOWVNWZRIQAUAD-UHFFFAOYSA-N 0.000 description 1
• XIVPOSPGHZNAOU-UHFFFAOYSA-N tert-butyl n-[2-(5-bromo-2-nitroanilino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNC1=CC(Br)=CC=C1[N+]([O-])=O XIVPOSPGHZNAOU-UHFFFAOYSA-N 0.000 description 1
• XXPDFYRRRCZYDW-UHFFFAOYSA-N tert-butyl n-[2-[[6-[(3,4-dichlorophenyl)methylamino]-3-nitropyridin-2-yl]amino]ethyl]carbamate Chemical compound C1=C([N+]([O-])=O)C(NCCNC(=O)OC(C)(C)C)=NC(NCC=2C=C(Cl)C(Cl)=CC=2)=C1 XXPDFYRRRCZYDW-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 230000003868 tissue accumulation Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 125000005259 triarylamine group Chemical group 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1