CA2653056A1 - Aldh-2 inhibitors in the treatment of addiction - Google Patents

Info

Publication number

CA2653056A1

CA2653056A1 CA002653056A CA2653056A CA2653056A1 CA 2653056 A1 CA2653056 A1 CA 2653056A1 CA 002653056 A CA002653056 A CA 002653056A CA 2653056 A CA2653056 A CA 2653056A CA 2653056 A1 CA2653056 A1 CA 2653056A1

Authority

CA

Canada

Prior art keywords

chromen

hydroxyphenyl

phenyl

methoxy

trifluoromethyl

Prior art date

2006-07-27

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 206010012335 Dependence Diseases 0.000 title abstract description 14
• 239000003112 inhibitor Substances 0.000 title abstract description 11
• 238000011282 treatment Methods 0.000 title description 24
• -1 amphetamines Chemical compound 0.000 claims abstract description 139
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims abstract description 76
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 68
• 229960003920 cocaine Drugs 0.000 claims abstract description 38
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims abstract description 23
• 229960002715 nicotine Drugs 0.000 claims abstract description 23
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims abstract description 23
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 20
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
• 229960003638 dopamine Drugs 0.000 claims abstract description 10
• 241000124008 Mammalia Species 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 300
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
• 125000000217 alkyl group Chemical group 0.000 claims description 93
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 72
• 125000001072 heteroaryl group Chemical group 0.000 claims description 71
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 67
• 239000001257 hydrogen Substances 0.000 claims description 58
• 229910052739 hydrogen Inorganic materials 0.000 claims description 58
• 125000003118 aryl group Chemical group 0.000 claims description 54
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
• 125000001424 substituent group Chemical group 0.000 claims description 51
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
• 238000000034 method Methods 0.000 claims description 38
• 125000003545 alkoxy group Chemical group 0.000 claims description 37
• 229910052760 oxygen Inorganic materials 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 34
• 150000002367 halogens Chemical group 0.000 claims description 34
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 33
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
• 239000001301 oxygen Substances 0.000 claims description 33
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 125000002947 alkylene group Chemical group 0.000 claims description 25
• 125000003342 alkenyl group Chemical group 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 125000000304 alkynyl group Chemical group 0.000 claims description 20
• YYOOFJZTRCPVFD-UHFFFAOYSA-N 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O YYOOFJZTRCPVFD-UHFFFAOYSA-N 0.000 claims description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
• GEOFIVBSXPVRPE-UHFFFAOYSA-N 3-[3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,2,4-oxadiazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)N=2)=C1 GEOFIVBSXPVRPE-UHFFFAOYSA-N 0.000 claims description 8
• ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• XINYOLXTIGKVRM-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-oxo-2-[2-(trifluoromethyl)phenyl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)C=3C(=CC=CC=3)C(F)(F)F)=CC=C2C1=O XINYOLXTIGKVRM-UHFFFAOYSA-N 0.000 claims description 7
• FYMBTIMJLANAIU-UHFFFAOYSA-N 7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O FYMBTIMJLANAIU-UHFFFAOYSA-N 0.000 claims description 7
• HEOQQDCLAMIWDE-UHFFFAOYSA-N 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzonitrile Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C#N)=CC=C2C1=O HEOQQDCLAMIWDE-UHFFFAOYSA-N 0.000 claims description 6
• YEVVMGQTIHYLHJ-CYBMUJFWSA-N 7-[(1r)-1-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound O([C@H](C)C=1ON=C(N=1)C=1C=C(C=C(F)C=1)C(F)(F)F)C(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 YEVVMGQTIHYLHJ-CYBMUJFWSA-N 0.000 claims description 6
• 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Chemical group N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
• 125000004193 piperazinyl group Chemical group 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 239000011593 sulfur Chemical group 0.000 claims description 6
• QXODMLJSSSYMLK-UHFFFAOYSA-N 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxy-n-[2-(trifluoromethyl)phenyl]acetamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)NC=3C(=CC=CC=3)C(F)(F)F)=CC=C2C1=O QXODMLJSSSYMLK-UHFFFAOYSA-N 0.000 claims description 5
• BISVYANBIFBJIA-UHFFFAOYSA-N 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxy-n-[3-(trifluoromethyl)phenyl]acetamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)NC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O BISVYANBIFBJIA-UHFFFAOYSA-N 0.000 claims description 5
• SKVYHLULOMUGKX-UHFFFAOYSA-N 2-fluoro-5-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=C(C(F)=CC=5)C#N)=CO4)=O)=CC=3)N=2)=C1 SKVYHLULOMUGKX-UHFFFAOYSA-N 0.000 claims description 5
• UIUCEBUXYPDPAJ-UHFFFAOYSA-N 3-(3-acetylphenyl)-7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound CC(=O)C1=CC=CC(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)=C1 UIUCEBUXYPDPAJ-UHFFFAOYSA-N 0.000 claims description 5
• GFHOVQHRHREPPZ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(3-phenylpropoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCCC=3C=CC=CC=3)=CC=C2C1=O GFHOVQHRHREPPZ-UHFFFAOYSA-N 0.000 claims description 5
• FXSYGQPEYZJTHI-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3OC(=NN=3)C=3C=NC=CC=3)=CC=C2C1=O FXSYGQPEYZJTHI-UHFFFAOYSA-N 0.000 claims description 5
• GUZLXSMJFYJQFJ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-(5-pyridin-4-yl-1,2,4-oxadiazol-3-yl)ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3N=C(ON=3)C=3C=CN=CC=3)=CC=C2C1=O GUZLXSMJFYJQFJ-UHFFFAOYSA-N 0.000 claims description 5
• MGBNIYZXARWXHW-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(N=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O MGBNIYZXARWXHW-UHFFFAOYSA-N 0.000 claims description 5
• JGOMKMRNUIOXIC-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O JGOMKMRNUIOXIC-UHFFFAOYSA-N 0.000 claims description 5
• NXRZHVXCUDNZGL-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[6-(1h-pyrazol-5-yl)pyridin-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=NC(=CC=3)C3=NNC=C3)=CC=C2C1=O NXRZHVXCUDNZGL-UHFFFAOYSA-N 0.000 claims description 5
• XAYXXBMMIHLDQI-UHFFFAOYSA-N 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=C1 XAYXXBMMIHLDQI-UHFFFAOYSA-N 0.000 claims description 5
• JUCBBVFEJTVYFD-UHFFFAOYSA-N 4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O JUCBBVFEJTVYFD-UHFFFAOYSA-N 0.000 claims description 5
• HSTCXSZUDZOKRP-UHFFFAOYSA-N 7-[2-(3-fluorophenyl)-2-oxoethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)C=3C=C(F)C=CC=3)=CC=C2C1=O HSTCXSZUDZOKRP-UHFFFAOYSA-N 0.000 claims description 5
• RKGISUHWZBBCKR-UHFFFAOYSA-N 7-[2-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3ON=C(N=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O RKGISUHWZBBCKR-UHFFFAOYSA-N 0.000 claims description 5
• VQLYYLNXOIUOFU-UHFFFAOYSA-N 7-[[5-(4-chlorophenyl)-1,2-oxazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O VQLYYLNXOIUOFU-UHFFFAOYSA-N 0.000 claims description 5
• FAHBJKISWFYSTG-UHFFFAOYSA-N 7-[[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=CC(F)=CC=3)=CC=C2C1=O FAHBJKISWFYSTG-UHFFFAOYSA-N 0.000 claims description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• PNNQLSVOFZVQDZ-OAHLLOKOSA-N n-[(1r)-1-(4-fluorophenyl)ethyl]-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyacetamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 PNNQLSVOFZVQDZ-OAHLLOKOSA-N 0.000 claims description 5
• PNNQLSVOFZVQDZ-HNNXBMFYSA-N n-[(1s)-1-(4-fluorophenyl)ethyl]-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyacetamide Chemical compound N([C@@H](C)C=1C=CC(F)=CC=1)C(=O)COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 PNNQLSVOFZVQDZ-HNNXBMFYSA-N 0.000 claims description 5
• FIFFBIMRAZGZIN-UHFFFAOYSA-N n-[4-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(NS(C)(=O)=O)C=C1 FIFFBIMRAZGZIN-UHFFFAOYSA-N 0.000 claims description 5
• QXYPVJQYTBVSBE-UHFFFAOYSA-N n-[4-[7-[[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=CC(F)=CC=3)=CC=C2C1=O QXYPVJQYTBVSBE-UHFFFAOYSA-N 0.000 claims description 5
• 239000000126 substance Substances 0.000 claims description 5
• JUEBRUJMZIBZFF-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O JUEBRUJMZIBZFF-UHFFFAOYSA-N 0.000 claims description 4
• DRKCCZCIUDIJGT-UHFFFAOYSA-N 3-[3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,2,4-oxadiazol-5-yl]benzonitrile Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C#N)=CC=C2C1=O DRKCCZCIUDIJGT-UHFFFAOYSA-N 0.000 claims description 4
• WCTAYNZYWWPMBP-UHFFFAOYSA-N 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(N)=O)=CC=C2C1=O WCTAYNZYWWPMBP-UHFFFAOYSA-N 0.000 claims description 4
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
• UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical group C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 4
• 101100240527 Caenorhabditis elegans nhr-22 gene Proteins 0.000 claims description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 4
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
• FKSRMBLWEXMUQH-UHFFFAOYSA-N methyl 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=C1 FKSRMBLWEXMUQH-UHFFFAOYSA-N 0.000 claims description 4
• IXNLDMMIZOOUOV-UHFFFAOYSA-N n-[4-[7-[(3-cyanophenyl)methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C#N)=CC=C2C1=O IXNLDMMIZOOUOV-UHFFFAOYSA-N 0.000 claims description 4
• 229940127240 opiate Drugs 0.000 claims description 4
• RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 claims description 4
• YARRGUWVCVLKCS-UHFFFAOYSA-N 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=N1 YARRGUWVCVLKCS-UHFFFAOYSA-N 0.000 claims description 3
• QZQVAPKTAUQPCF-UHFFFAOYSA-N 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-N-methyl-1,3-oxazole-4-carboxamide Chemical compound CNC(=O)C1=COC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=N1 QZQVAPKTAUQPCF-UHFFFAOYSA-N 0.000 claims description 3
• ZJWNWERIHPKYCW-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(2-phenylethoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3C=CC=CC=3)=CC=C2C1=O ZJWNWERIHPKYCW-UHFFFAOYSA-N 0.000 claims description 3
• CTTKSJXFCLZWEY-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(2-piperazin-1-ylethoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCNCC3)=CC=C2C1=O CTTKSJXFCLZWEY-UHFFFAOYSA-N 0.000 claims description 3
• GABUIDRLSZLRFS-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(pyridin-2-ylmethoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=CC=CC=3)=CC=C2C1=O GABUIDRLSZLRFS-UHFFFAOYSA-N 0.000 claims description 3
• LYOPHGBGGFBIAP-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(pyridin-4-ylmethoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=CN=CC=3)=CC=C2C1=O LYOPHGBGGFBIAP-UHFFFAOYSA-N 0.000 claims description 3
• SGWYZMJMBDTNPE-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(3-phenyl-1,2,4-oxadiazol-5-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(N=3)C=3C=CC=CC=3)=CC=C2C1=O SGWYZMJMBDTNPE-UHFFFAOYSA-N 0.000 claims description 3
• GQHHGMIEWPYQLZ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(N=3)C=3C=NC=CC=3)=CC=C2C1=O GQHHGMIEWPYQLZ-UHFFFAOYSA-N 0.000 claims description 3
• FFXQJURUOMILQH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-phenyl-1,2,4-oxadiazol-3-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=CC=CC=3)=CC=C2C1=O FFXQJURUOMILQH-UHFFFAOYSA-N 0.000 claims description 3
• NPDZVHPRRHSDIJ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-pyridin-2-yl-1,2,4-oxadiazol-3-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3N=CC=CC=3)=CC=C2C1=O NPDZVHPRRHSDIJ-UHFFFAOYSA-N 0.000 claims description 3
• AHYUTGIZIZIDKP-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-pyridin-2-yl-1,2-oxazol-3-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3N=CC=CC=3)=CC=C2C1=O AHYUTGIZIZIDKP-UHFFFAOYSA-N 0.000 claims description 3
• BLMUWBUJDTZGQV-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=NC=CC=3)=CC=C2C1=O BLMUWBUJDTZGQV-UHFFFAOYSA-N 0.000 claims description 3
• XDBUTBAUTWQRHY-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=NC=CC=3)=CC=C2C1=O XDBUTBAUTWQRHY-UHFFFAOYSA-N 0.000 claims description 3
• HKEWKJSYDITCPM-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-(5-pyridin-2-yl-1,2,4-oxadiazol-3-yl)ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3N=C(ON=3)C=3N=CC=CC=3)=CC=C2C1=O HKEWKJSYDITCPM-UHFFFAOYSA-N 0.000 claims description 3
• AFPFBJUMGHWWSF-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-(5-pyridin-3-yl-1,2,4-oxadiazol-3-yl)ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3N=C(ON=3)C=3C=NC=CC=3)=CC=C2C1=O AFPFBJUMGHWWSF-UHFFFAOYSA-N 0.000 claims description 3
• HKXIGXKVBVSHLZ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[3-(trifluoromethyl)phenyl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O HKXIGXKVBVSHLZ-UHFFFAOYSA-N 0.000 claims description 3
• PMIDRXUFPZSRBZ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound C1=CC(OC)=CC=C1N1CCN(CCOC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)CC1 PMIDRXUFPZSRBZ-UHFFFAOYSA-N 0.000 claims description 3
• YBRCUCDVZMFQDL-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O YBRCUCDVZMFQDL-UHFFFAOYSA-N 0.000 claims description 3
• NLBVKHVFWSBBEC-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[5-(trifluoromethyl)-1h-pyrazol-4-yl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC3=C(NN=C3)C(F)(F)F)=CC=C2C1=O NLBVKHVFWSBBEC-UHFFFAOYSA-N 0.000 claims description 3
• ZLHYZFVZAFHBEA-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[[3-(trifluoromethyl)phenyl]methylamino]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCNCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O ZLHYZFVZAFHBEA-UHFFFAOYSA-N 0.000 claims description 3
• BXQJHBUPOKYULL-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[2-(3,4,5-trifluorophenyl)-1,3-oxazol-4-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(F)C(F)=C(F)C=3)=CC=C2C1=O BXQJHBUPOKYULL-UHFFFAOYSA-N 0.000 claims description 3
• NVHXGZBXAVVPFO-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[2-[3-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O NVHXGZBXAVVPFO-UHFFFAOYSA-N 0.000 claims description 3
• XZZGBJWFXVPVMV-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-(2h-tetrazol-5-yl)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C=3NN=NN=3)=CC=C2C1=O XZZGBJWFXVPVMV-UHFFFAOYSA-N 0.000 claims description 3
• CBQSSDNKQRPHMZ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O CBQSSDNKQRPHMZ-UHFFFAOYSA-N 0.000 claims description 3
• IJKBDDMBAHSXDV-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]chromen-4-one Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 IJKBDDMBAHSXDV-UHFFFAOYSA-N 0.000 claims description 3
• PHGCOEMZEZPYOR-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(3-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound COC1=CC=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)N=2)=C1 PHGCOEMZEZPYOR-UHFFFAOYSA-N 0.000 claims description 3
• WVGOFTXJQXXJEP-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[3-(2h-tetrazol-5-yl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C=3NN=NN=3)=CC=C2C1=O WVGOFTXJQXXJEP-UHFFFAOYSA-N 0.000 claims description 3
• IUQDULUMXAXWBP-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O IUQDULUMXAXWBP-UHFFFAOYSA-N 0.000 claims description 3
• DSNYSUDIVYIEQH-UHFFFAOYSA-N 3-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=C(C=CC=5)C#N)=CO4)=O)=CC=3)N=2)=C1 DSNYSUDIVYIEQH-UHFFFAOYSA-N 0.000 claims description 3
• JNOYBALWQJYPES-UHFFFAOYSA-N 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzamide Chemical compound NC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(N)=CC=4)=CO3)=O)=CC=2)=C1 JNOYBALWQJYPES-UHFFFAOYSA-N 0.000 claims description 3
• WVKZSEGADHUEKE-UHFFFAOYSA-N 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzonitrile Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C#N)=CC=C2C1=O WVKZSEGADHUEKE-UHFFFAOYSA-N 0.000 claims description 3
• IMLRTJCRZHHKRW-UHFFFAOYSA-N 4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O IMLRTJCRZHHKRW-UHFFFAOYSA-N 0.000 claims description 3
• XJKPZYKFZKQYCH-UHFFFAOYSA-N 4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(=CC=5)C#N)=CO4)=O)=CC=3)N=2)=C1 XJKPZYKFZKQYCH-UHFFFAOYSA-N 0.000 claims description 3
• QPSPVQPYOAKFBC-UHFFFAOYSA-N 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 QPSPVQPYOAKFBC-UHFFFAOYSA-N 0.000 claims description 3
• IYDPWNALDNSKDN-UHFFFAOYSA-N 4-methyl-n-[4-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]phenyl]benzenesulfonamide Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1COC(C=1)=CC=C(C2=O)C=1OC=C2C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 IYDPWNALDNSKDN-UHFFFAOYSA-N 0.000 claims description 3
• YEVVMGQTIHYLHJ-ZDUSSCGKSA-N 7-[(1s)-1-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound O([C@@H](C)C=1ON=C(N=1)C=1C=C(C=C(F)C=1)C(F)(F)F)C(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 YEVVMGQTIHYLHJ-ZDUSSCGKSA-N 0.000 claims description 3
• ORRIPWVLGBZIDZ-UHFFFAOYSA-N 7-[2-(4-chlorophenoxy)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCOC=3C=CC(Cl)=CC=3)=CC=C2C1=O ORRIPWVLGBZIDZ-UHFFFAOYSA-N 0.000 claims description 3
• FAAGZNJVSVYNSW-UHFFFAOYSA-N 7-[2-(4-fluorophenyl)-2-oxoethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)C=3C=CC(F)=CC=3)=CC=C2C1=O FAAGZNJVSVYNSW-UHFFFAOYSA-N 0.000 claims description 3
• XFAQSZLKVGZYAA-UHFFFAOYSA-N 7-[2-(4-fluorophenyl)ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3C=CC(F)=CC=3)=CC=C2C1=O XFAQSZLKVGZYAA-UHFFFAOYSA-N 0.000 claims description 3
• KFKDUJLKVAOFQB-UHFFFAOYSA-N 7-[2-[2-(4-fluorophenyl)ethylamino]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCNCCC=3C=CC(F)=CC=3)=CC=C2C1=O KFKDUJLKVAOFQB-UHFFFAOYSA-N 0.000 claims description 3
• HHONJABIGAPPKM-UHFFFAOYSA-N 7-[2-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]propan-2-yloxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound N=1C(C=2C=C(C=C(F)C=2)C(F)(F)F)=NOC=1C(C)(C)OC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 HHONJABIGAPPKM-UHFFFAOYSA-N 0.000 claims description 3
• JAGZCQBDQUBNEH-UHFFFAOYSA-N 7-[2-[4-(3-chlorophenyl)piperazin-1-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C=C(Cl)C=CC=3)=CC=C2C1=O JAGZCQBDQUBNEH-UHFFFAOYSA-N 0.000 claims description 3
• KVDVZUSHUNMBDO-UHFFFAOYSA-N 7-[2-[4-(4-chlorophenyl)-1h-pyrazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3C(=CNN=3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O KVDVZUSHUNMBDO-UHFFFAOYSA-N 0.000 claims description 3
• SXFJOYLSGKZQEM-UHFFFAOYSA-N 7-[2-[4-(4-fluorophenyl)piperazin-1-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C=CC(F)=CC=3)=CC=C2C1=O SXFJOYLSGKZQEM-UHFFFAOYSA-N 0.000 claims description 3
• CVHDDJFLECTRJK-UHFFFAOYSA-N 7-[2-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3OC(=NN=3)C=3C=CC(F)=CC=3)=CC=C2C1=O CVHDDJFLECTRJK-UHFFFAOYSA-N 0.000 claims description 3
• MKMPNJBMKLCURY-UHFFFAOYSA-N 7-[3-[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]propoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O MKMPNJBMKLCURY-UHFFFAOYSA-N 0.000 claims description 3
• PCKCUVRYWBKTEA-UHFFFAOYSA-N 7-[[2-(3,4-difluorophenyl)-1,3-oxazol-4-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(F)C(F)=CC=3)=CC=C2C1=O PCKCUVRYWBKTEA-UHFFFAOYSA-N 0.000 claims description 3
• COLMHOKXSWZSER-UHFFFAOYSA-N 7-[[2-(3,5-difluorophenyl)-1,3-oxazol-4-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(F)C=C(F)C=3)=CC=C2C1=O COLMHOKXSWZSER-UHFFFAOYSA-N 0.000 claims description 3
• JKGRQKQIEYBYTJ-UHFFFAOYSA-N 7-[[2-(4-chlorophenyl)-1,3-oxazol-4-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O JKGRQKQIEYBYTJ-UHFFFAOYSA-N 0.000 claims description 3
• WEUVQMIOXQPDCT-UHFFFAOYSA-N 7-[[2-(4-fluorophenyl)-1,3-oxazol-4-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=CC(F)=CC=3)=CC=C2C1=O WEUVQMIOXQPDCT-UHFFFAOYSA-N 0.000 claims description 3
• NFLMVGPBVSJOKQ-UHFFFAOYSA-N 7-[[3-fluoro-5-(trifluoromethyl)phenyl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O NFLMVGPBVSJOKQ-UHFFFAOYSA-N 0.000 claims description 3
• MOSZHACXXNIKAF-UHFFFAOYSA-N 7-[[5-(2-chlorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C(=CC=CC=3)Cl)=CC=C2C1=O MOSZHACXXNIKAF-UHFFFAOYSA-N 0.000 claims description 3
• YBAAQOVRDFBILI-UHFFFAOYSA-N 7-[[5-(3,4-dichlorophenyl)-1,2-oxazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3C=C(Cl)C(Cl)=CC=3)=CC=C2C1=O YBAAQOVRDFBILI-UHFFFAOYSA-N 0.000 claims description 3
• GZQHEBGZIKUMDM-UHFFFAOYSA-N 7-[[5-(3-fluorophenyl)-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(F)C=CC=3)=CC=C2C1=O GZQHEBGZIKUMDM-UHFFFAOYSA-N 0.000 claims description 3
• BPVYYYUTPWPBES-UHFFFAOYSA-N 7-[[5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=C(F)C=CC=3)=CC=C2C1=O BPVYYYUTPWPBES-UHFFFAOYSA-N 0.000 claims description 3
• WMYIPPDFUUZWRA-UHFFFAOYSA-N 7-[[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=CC(F)=CC=3)=CC=C2C1=O WMYIPPDFUUZWRA-UHFFFAOYSA-N 0.000 claims description 3
• TZRVABAXGZCOOH-UHFFFAOYSA-N 7-[[5-[2,5-bis(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C(=CC=C(C=3)C(F)(F)F)C(F)(F)F)=CC=C2C1=O TZRVABAXGZCOOH-UHFFFAOYSA-N 0.000 claims description 3
• NPGQORNIHHVBJO-UHFFFAOYSA-N 7-[[5-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)=CC=C2C1=O NPGQORNIHHVBJO-UHFFFAOYSA-N 0.000 claims description 3
• CDZYCQRKIXMTJK-UHFFFAOYSA-N 7-[[5-[3,5-bis(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)=CC=C2C1=O CDZYCQRKIXMTJK-UHFFFAOYSA-N 0.000 claims description 3
• GVOQTGJRDTXIMR-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O GVOQTGJRDTXIMR-UHFFFAOYSA-N 0.000 claims description 3
• 229910007161 Si(CH3)3 Inorganic materials 0.000 claims description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
• AAWXSHHENRRQRE-UHFFFAOYSA-N ethyl 1-[2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1CCOC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 AAWXSHHENRRQRE-UHFFFAOYSA-N 0.000 claims description 3
• GKIIYMRXUSLEFZ-UHFFFAOYSA-N ethyl 4-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=COC2=CC(OCC3=C(N=C(S3)C=3C=CC(=CC=3)C(F)(F)F)C)=CC=C2C1=O GKIIYMRXUSLEFZ-UHFFFAOYSA-N 0.000 claims description 3
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
• XCGPDNAYSXIGBN-UHFFFAOYSA-N methyl 3-[[3-[4-(hydroxymethyl)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(CO)=CC=4)=CO3)=O)=CC=2)=C1 XCGPDNAYSXIGBN-UHFFFAOYSA-N 0.000 claims description 3
• GGWNBYMSLMPZCF-UHFFFAOYSA-N methyl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(C)(=O)=O)=CC=4)=CO3)=O)=CC=2)=C1 GGWNBYMSLMPZCF-UHFFFAOYSA-N 0.000 claims description 3
• ZPUAMDNSBAFJTB-UHFFFAOYSA-N n-(2,4-difluorophenyl)-4-[2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]piperazine-1-carboxamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C(=O)NC=3C(=CC(F)=CC=3)F)=CC=C2C1=O ZPUAMDNSBAFJTB-UHFFFAOYSA-N 0.000 claims description 3
• IEHKIQDJTOPPTN-UHFFFAOYSA-N n-(3-fluorophenyl)-2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyacetamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)NC=3C=C(F)C=CC=3)=CC=C2C1=O IEHKIQDJTOPPTN-UHFFFAOYSA-N 0.000 claims description 3
• SZCZFEMWSJXEAC-UHFFFAOYSA-N n-(3-fluorophenyl)-4-[2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]piperazine-1-carboxamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C(=O)NC=3C=C(F)C=CC=3)=CC=C2C1=O SZCZFEMWSJXEAC-UHFFFAOYSA-N 0.000 claims description 3
• FNYQPJGJSIQOQK-UHFFFAOYSA-N n-[4-[4-oxo-7-[(2-phenyl-1,3-oxazol-4-yl)methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=CC=CC=3)=CC=C2C1=O FNYQPJGJSIQOQK-UHFFFAOYSA-N 0.000 claims description 3
• ARHPCVRPEMHVFN-UHFFFAOYSA-N n-[4-[4-oxo-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O ARHPCVRPEMHVFN-UHFFFAOYSA-N 0.000 claims description 3
• SCXVTUJUIPDVJB-UHFFFAOYSA-N n-[4-[7-[[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=CC(F)=CC=3)=CC=C2C1=O SCXVTUJUIPDVJB-UHFFFAOYSA-N 0.000 claims description 3
• QVZCPNUNJCOGGA-UHFFFAOYSA-N propan-2-yl 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CC(C)OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=C1 QVZCPNUNJCOGGA-UHFFFAOYSA-N 0.000 claims description 3
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 claims description 2
• TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 claims description 2
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical group N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 claims description 2
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical group C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 2
• OESBYEICGXYNBT-UHFFFAOYSA-N 3-(4-aminophenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O OESBYEICGXYNBT-UHFFFAOYSA-N 0.000 claims description 2
• MLHOACBDJNPKJC-UHFFFAOYSA-N 3-(4-aminophenyl)-7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O MLHOACBDJNPKJC-UHFFFAOYSA-N 0.000 claims description 2
• BCHLRGSTGMUSFO-UHFFFAOYSA-N 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O BCHLRGSTGMUSFO-UHFFFAOYSA-N 0.000 claims description 2
• GIKCZRQTBXPKGV-UHFFFAOYSA-N 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzamide Chemical compound NC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=C1 GIKCZRQTBXPKGV-UHFFFAOYSA-N 0.000 claims description 2
• VFKSORDIMAUFFL-UHFFFAOYSA-N 4-(oxathian-3-yl)morpholine Chemical group O1SC(CCC1)N1CCOCC1 VFKSORDIMAUFFL-UHFFFAOYSA-N 0.000 claims description 2
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical group C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 claims description 2
• KAJPBUYABCQBKK-UHFFFAOYSA-N 7-[2-[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O KAJPBUYABCQBKK-UHFFFAOYSA-N 0.000 claims description 2
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
• AMJINJSTVXQTMD-UHFFFAOYSA-N [4-[7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-4-oxochromen-3-yl]phenyl] dihydrogen phosphate Chemical compound C1=CC(OP(O)(=O)O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O AMJINJSTVXQTMD-UHFFFAOYSA-N 0.000 claims description 2
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical group N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical group C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 2
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
• IVLDGUKVQHCQCA-UHFFFAOYSA-N methyl 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=N1 IVLDGUKVQHCQCA-UHFFFAOYSA-N 0.000 claims description 2
• CFXFFAFGWRNMJV-UHFFFAOYSA-N methyl 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 CFXFFAFGWRNMJV-UHFFFAOYSA-N 0.000 claims description 2
• PMXLLFNDTDRGFI-UHFFFAOYSA-N n-[4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O PMXLLFNDTDRGFI-UHFFFAOYSA-N 0.000 claims description 2
• 150000002916 oxazoles Chemical class 0.000 claims description 2
• 229950000688 phenothiazine Drugs 0.000 claims description 2
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical group C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 claims description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical group N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 6
• 125000001475 halogen functional group Chemical group 0.000 claims 5
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• DKYBVKMIZODYKL-UHFFFAOYSA-N 1,3-diazinane Chemical compound C1CNCNC1 DKYBVKMIZODYKL-UHFFFAOYSA-N 0.000 claims 1
• QYQCFHLVHVSJTA-UHFFFAOYSA-N 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzonitrile Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C(=CC=CC=3)C#N)=CC=C2C1=O QYQCFHLVHVSJTA-UHFFFAOYSA-N 0.000 claims 1
• NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 claims 1
• DKTXNAYSCCZCGS-UHFFFAOYSA-N 2-trimethylsilylethyl 3-[[3-(3-cyanophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C[Si](C)(C)CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=C(C=CC=4)C#N)=CO3)=O)=CC=2)=C1 DKTXNAYSCCZCGS-UHFFFAOYSA-N 0.000 claims 1
• LNLIHPSCCYLOHF-UHFFFAOYSA-N 2-trimethylsilylethyl 3-[[3-(4-carbamoylphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C[Si](C)(C)CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)C(N)=O)=CO3)=O)=CC=2)=C1 LNLIHPSCCYLOHF-UHFFFAOYSA-N 0.000 claims 1
• ZACMAZHZBBJEFO-UHFFFAOYSA-N 2-trimethylsilylethyl 3-[[3-[3-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C[Si](C)(C)CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=C(NS(C)(=O)=O)C=CC=4)=CO3)=O)=CC=2)=C1 ZACMAZHZBBJEFO-UHFFFAOYSA-N 0.000 claims 1
• CNFOIZLFPBENBM-UHFFFAOYSA-N 3-(3-fluorophenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound FC1=CC=CC(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=CC=4)C(F)(F)F)C=C3OC=2)=O)=C1 CNFOIZLFPBENBM-UHFFFAOYSA-N 0.000 claims 1
• XUJUWOOYHUYKRF-UHFFFAOYSA-N 3-(4-aminophenyl)-7-[[3-(trifluoromethoxy)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3C=C(OC(F)(F)F)C=CC=3)=CC=C2C1=O XUJUWOOYHUYKRF-UHFFFAOYSA-N 0.000 claims 1
• QVCQIPUPLJTJKR-UHFFFAOYSA-N 3-(4-aminophenyl)-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O QVCQIPUPLJTJKR-UHFFFAOYSA-N 0.000 claims 1
• USHIWOJJGWWHKC-UHFFFAOYSA-N 3-(4-fluorophenyl)-7-[[5-(2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound COC1=CC=CC=C1C1=NC(COC=2C=C3C(C(C(C=4C=CC(F)=CC=4)=CO3)=O)=CC=2)=NO1 USHIWOJJGWWHKC-UHFFFAOYSA-N 0.000 claims 1
• RBCQQVFEINHKDD-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2-(trifluoromethyl)-6-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C(C(C1=C2)=O)=C(C(F)(F)F)OC1=CC=C2OCC1=NOC(C=2C=C(C=CC=2)C(F)(F)F)=N1 RBCQQVFEINHKDD-UHFFFAOYSA-N 0.000 claims 1
• UNYJSYKAFBRDSF-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-6-[[3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C(C(C1=C2)=O)=COC1=CC=C2OCC1=NC(C=2C=C(C=CC=2)C(F)(F)F)=NO1 UNYJSYKAFBRDSF-UHFFFAOYSA-N 0.000 claims 1
• IGLFEFCJHYKGNJ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-6-[[5-[4-methoxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-2-(trifluoromethyl)chromen-4-one Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C1=NC(COC=2C=C3C(=O)C(C=4C=CC(O)=CC=4)=C(OC3=CC=2)C(F)(F)F)=NO1 IGLFEFCJHYKGNJ-UHFFFAOYSA-N 0.000 claims 1
• BTNOQJRRJASMJW-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(pyridin-3-ylmethoxy)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=NC=CC=3)=CC=C2C1=O BTNOQJRRJASMJW-UHFFFAOYSA-N 0.000 claims 1
• MYLUNEORTANDOK-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(2-phenyl-1,3-oxazol-4-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=CC=CC=3)=CC=C2C1=O MYLUNEORTANDOK-UHFFFAOYSA-N 0.000 claims 1
• YBSGKKITPLSUPH-FQEVSTJZSA-N 3-(4-hydroxyphenyl)-7-[(2s)-2-hydroxy-3-[[3-(trifluoromethyl)phenyl]methylamino]propoxy]chromen-4-one Chemical compound C([C@H](O)COC=1C=C2C(C(C(C=3C=CC(O)=CC=3)=CO2)=O)=CC=1)NCC1=CC=CC(C(F)(F)F)=C1 YBSGKKITPLSUPH-FQEVSTJZSA-N 0.000 claims 1
• VIUAWBLQYVJXIW-IBGZPJMESA-N 3-(4-hydroxyphenyl)-7-[(2s)-2-hydroxy-3-phenylpropoxy]chromen-4-one Chemical compound C([C@@H](O)CC=1C=CC=CC=1)OC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 VIUAWBLQYVJXIW-IBGZPJMESA-N 0.000 claims 1
• QPOMIYFFWNHPDD-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(5-phenyl-1,2-oxazol-3-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC3=NOC(=C3)C=3C=CC=CC=3)=CC=C2C1=O QPOMIYFFWNHPDD-UHFFFAOYSA-N 0.000 claims 1
• FPUFUYUDPHGFEH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-(5-pyridin-4-yl-1,3,4-oxadiazol-2-yl)ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3OC(=NN=3)C=3C=CN=CC=3)=CC=C2C1=O FPUFUYUDPHGFEH-UHFFFAOYSA-N 0.000 claims 1
• XNRHIWZNASULGF-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound COC1=CC=CC=C1N1CCN(CCOC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)CC1 XNRHIWZNASULGF-UHFFFAOYSA-N 0.000 claims 1
• VOZPBFARGKFKDU-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(2-methylphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound CC1=CC=CC=C1N1CCN(CCOC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)CC1 VOZPBFARGKFKDU-UHFFFAOYSA-N 0.000 claims 1
• GKDBURVCBFZSCD-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(3-methoxyphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound COC1=CC=CC(N2CCN(CCOC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)CC2)=C1 GKDBURVCBFZSCD-UHFFFAOYSA-N 0.000 claims 1
• MVWFUJHZXMTRHS-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(3-methylphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound CC1=CC=CC(N2CCN(CCOC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)CC2)=C1 MVWFUJHZXMTRHS-UHFFFAOYSA-N 0.000 claims 1
• STVSMLYUQNAJLH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-(4-methylphenyl)piperazin-1-yl]ethoxy]chromen-4-one Chemical compound C1=CC(C)=CC=C1N1CCN(CCOC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)CC1 STVSMLYUQNAJLH-UHFFFAOYSA-N 0.000 claims 1
• KPWVMSRCNSRFBT-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-[2-(trifluoromethyl)phenyl]piperazin-1-yl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C(=CC=CC=3)C(F)(F)F)=CC=C2C1=O KPWVMSRCNSRFBT-UHFFFAOYSA-N 0.000 claims 1
• HABMRRNWPZNAHB-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O HABMRRNWPZNAHB-UHFFFAOYSA-N 0.000 claims 1
• QIMFQFMJFVNZFR-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-oxo-2-[4-(trifluoromethyl)phenyl]ethoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O QIMFQFMJFVNZFR-UHFFFAOYSA-N 0.000 claims 1
• ZPUVRABODOBSAH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-(trifluoromethoxy)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(OC(F)(F)F)C=CC=3)=CC=C2C1=O ZPUVRABODOBSAH-UHFFFAOYSA-N 0.000 claims 1
• XZWFEHFXGWFMKS-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-[3-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(C=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O XZWFEHFXGWFMKS-UHFFFAOYSA-N 0.000 claims 1
• VFUZTXQSDASORI-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound COC1=CC=CC=C1C(O1)=NN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 VFUZTXQSDASORI-UHFFFAOYSA-N 0.000 claims 1
• RMXOJOGIANOTSJ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound CC1=CC=CC=C1C(O1)=NN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 RMXOJOGIANOTSJ-UHFFFAOYSA-N 0.000 claims 1
• FUCKCJMQAGFLIF-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound COC1=CC=CC(C=2OC(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)=NN=2)=C1 FUCKCJMQAGFLIF-UHFFFAOYSA-N 0.000 claims 1
• SLDDEMWKXMOGSY-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(3-methylphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound CC1=CC=CC(C=2OC(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)=NN=2)=C1 SLDDEMWKXMOGSY-UHFFFAOYSA-N 0.000 claims 1
• SCIHYFZNPVIOOQ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(4-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=NC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=NO1 SCIHYFZNPVIOOQ-UHFFFAOYSA-N 0.000 claims 1
• VQAIBBQEMDSXGR-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound C1=CC(OC)=CC=C1C(O1)=NN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 VQAIBBQEMDSXGR-UHFFFAOYSA-N 0.000 claims 1
• ZRCYZRQZQQCIAK-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound C1=CC(C)=CC=C1C(O1)=NN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZRCYZRQZQQCIAK-UHFFFAOYSA-N 0.000 claims 1
• RKDOJVUCIUGPAG-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O RKDOJVUCIUGPAG-UHFFFAOYSA-N 0.000 claims 1
• KRTVXOPDCMVMGC-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[4-methoxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C1=NC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=NO1 KRTVXOPDCMVMGC-UHFFFAOYSA-N 0.000 claims 1
• YHHAYEWUUXQFOL-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[6-(trifluoromethyl)pyridin-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=NC(=CC=3)C(F)(F)F)=CC=C2C1=O YHHAYEWUUXQFOL-UHFFFAOYSA-N 0.000 claims 1
• PKGVXZWMYVCZNT-UHFFFAOYSA-N 3-(4-methoxyphenyl)-7-[[5-(2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C(=CC=CC=3)OC)=CC=C2C1=O PKGVXZWMYVCZNT-UHFFFAOYSA-N 0.000 claims 1
• RGQMOEXUFWMRLU-UHFFFAOYSA-N 3-(4-methylphenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(C)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O RGQMOEXUFWMRLU-UHFFFAOYSA-N 0.000 claims 1
• UZWQLFASQMHLAK-UHFFFAOYSA-N 3-[[2-hydroxy-3-[4-(methanesulfonamido)phenyl]-4-oxo-2,3-dihydrochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1C(=O)C2=CC=C(OCC=3C=C(C=CC=3)C(O)=O)C=C2OC1O UZWQLFASQMHLAK-UHFFFAOYSA-N 0.000 claims 1
• YAAKJWVORLBNTF-UHFFFAOYSA-N 3-[[3-(4-carbamoylphenyl)-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(C(=O)N)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O YAAKJWVORLBNTF-UHFFFAOYSA-N 0.000 claims 1
• DDMANHXIYQTENK-UHFFFAOYSA-N 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-N-[[3-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)NCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O DDMANHXIYQTENK-UHFFFAOYSA-N 0.000 claims 1
• ATRDANSWHPMPDB-UHFFFAOYSA-N 3-[[3-(4-methylsulfonylphenyl)-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O ATRDANSWHPMPDB-UHFFFAOYSA-N 0.000 claims 1
• KFLSGMZNSZFNAJ-UHFFFAOYSA-N 4-[4-oxo-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(=CC=5)C#N)=CO4)=O)=CC=3)N=2)=C1 KFLSGMZNSZFNAJ-UHFFFAOYSA-N 0.000 claims 1
• VFRTZXWTORJKEU-UHFFFAOYSA-N 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzonitrile Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C2C1=O VFRTZXWTORJKEU-UHFFFAOYSA-N 0.000 claims 1
• CXIIQPMREFANFO-UHFFFAOYSA-N 6-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)-2-(trifluoromethyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C(C(C1=C2)=O)=C(C(F)(F)F)OC1=CC=C2OCC1=NOC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 CXIIQPMREFANFO-UHFFFAOYSA-N 0.000 claims 1
• RPQZKJITPGRCKF-FQEVSTJZSA-N 7-[(2s)-2-hydroxy-3-[[3-(trifluoromethyl)phenyl]methylamino]propoxy]-3-(4-methoxyphenyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OC[C@@H](O)CNCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O RPQZKJITPGRCKF-FQEVSTJZSA-N 0.000 claims 1
• BHESGBIBNPDUJW-FQEVSTJZSA-N 7-[(2s)-3-[(3,5-difluorophenyl)methylamino]-2-hydroxypropoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C([C@H](O)COC=1C=C2C(C(C(C=3C=CC(O)=CC=3)=CO2)=O)=CC=1)NCC1=CC(F)=CC(F)=C1 BHESGBIBNPDUJW-FQEVSTJZSA-N 0.000 claims 1
• GUETZOYSPCKXKL-UHFFFAOYSA-N 7-[2-(4-fluorophenyl)-2-oxoethoxy]-3-(4-methoxyphenyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC(=O)C=3C=CC(F)=CC=3)=CC=C2C1=O GUETZOYSPCKXKL-UHFFFAOYSA-N 0.000 claims 1
• KORFTUYYDNQLIT-UHFFFAOYSA-N 7-[2-[3-(5-bromopyridin-3-yl)-1,2,4-oxadiazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3ON=C(N=3)C=3C=C(Br)C=NC=3)=CC=C2C1=O KORFTUYYDNQLIT-UHFFFAOYSA-N 0.000 claims 1
• YBMCDYRUWGLIEU-UHFFFAOYSA-N 7-[2-[4-(2-fluorophenyl)piperazin-1-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C(=CC=CC=3)F)=CC=C2C1=O YBMCDYRUWGLIEU-UHFFFAOYSA-N 0.000 claims 1
• HOPUHQHIURDXAS-UHFFFAOYSA-N 7-[2-[4-(3-fluorophenyl)piperazin-1-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C=3C=C(F)C=CC=3)=CC=C2C1=O HOPUHQHIURDXAS-UHFFFAOYSA-N 0.000 claims 1
• LVBYYSGNQQWIJS-UHFFFAOYSA-N 7-[3-[(3,5-difluorophenyl)methylamino]-2-hydroxypropoxy]-3-(4-methoxyphenyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC(O)CNCC=3C=C(F)C=C(F)C=3)=CC=C2C1=O LVBYYSGNQQWIJS-UHFFFAOYSA-N 0.000 claims 1
• TVYQUGOSXLQOGP-UHFFFAOYSA-N 7-[[3-(3-aminophenyl)-1,2,4-oxadiazol-5-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound NC1=CC=CC(C=2N=C(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)ON=2)=C1 TVYQUGOSXLQOGP-UHFFFAOYSA-N 0.000 claims 1
• IBRIBDVVLALIBW-UHFFFAOYSA-N 7-[[3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methoxy]-3-[4-[[3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methoxy]phenyl]chromen-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(COC=3C=CC(=CC=3)C=3C(C4=CC=C(OCC=5ON=C(N=5)C=5C=C(C=CC=5)C(F)(F)F)C=C4OC=3)=O)ON=2)=C1 IBRIBDVVLALIBW-UHFFFAOYSA-N 0.000 claims 1
• BYZRPKNYQMQCMK-UHFFFAOYSA-N 7-[[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(N=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O BYZRPKNYQMQCMK-UHFFFAOYSA-N 0.000 claims 1
• WHBOOUQLMQINPB-UHFFFAOYSA-N 7-[[5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=C(Cl)C=CC=3)=CC=C2C1=O WHBOOUQLMQINPB-UHFFFAOYSA-N 0.000 claims 1
• VVVFLKUGSGNQNY-UHFFFAOYSA-N 7-[[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O VVVFLKUGSGNQNY-UHFFFAOYSA-N 0.000 claims 1
• YYGCAYSDPMCHAO-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-methylsulfonylphenyl)chromen-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O YYGCAYSDPMCHAO-UHFFFAOYSA-N 0.000 claims 1
• RKVAGAXJZJFEDQ-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-[4-(hydroxymethyl)phenyl]chromen-4-one Chemical compound C1=CC(CO)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O RKVAGAXJZJFEDQ-UHFFFAOYSA-N 0.000 claims 1
• WBLWOFGQAXLTRU-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NN=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O WBLWOFGQAXLTRU-UHFFFAOYSA-N 0.000 claims 1
• CLFPJUWQTLWOEP-UHFFFAOYSA-N 7-[[5-[4-fluoro-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C(F)=CC=3)C(F)(F)F)=CC=C2C1=O CLFPJUWQTLWOEP-UHFFFAOYSA-N 0.000 claims 1
• WNYYVTUGJCLMLU-UHFFFAOYSA-N 7-[[6-(trifluoromethyl)pyridin-3-yl]methoxy]-3-[4-[[6-(trifluoromethyl)pyridin-3-yl]methoxy]phenyl]chromen-4-one Chemical compound C1=NC(C(F)(F)F)=CC=C1COC1=CC=C(C=2C(C3=CC=C(OCC=4C=NC(=CC=4)C(F)(F)F)C=C3OC=2)=O)C=C1 WNYYVTUGJCLMLU-UHFFFAOYSA-N 0.000 claims 1
• YFTSDZIXAMNCEZ-UHFFFAOYSA-N [3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=C1 YFTSDZIXAMNCEZ-UHFFFAOYSA-N 0.000 claims 1
• YZSKYZCRDKDSRB-UHFFFAOYSA-N [4-[7-[(3-methoxycarbonylphenyl)methoxy]-4-oxochromen-3-yl]phenyl]boronic acid Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)B(O)O)=CO3)=O)=CC=2)=C1 YZSKYZCRDKDSRB-UHFFFAOYSA-N 0.000 claims 1
• RPZVGHWHHUBQPE-UHFFFAOYSA-N [4-[7-[2-[3-[2-fluoro-4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-4-oxochromen-3-yl]phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=COC2=CC(OCCC=3ON=C(N=3)C=3C(=CC(=CC=3)C(F)(F)F)F)=CC=C2C1=O RPZVGHWHHUBQPE-UHFFFAOYSA-N 0.000 claims 1
• NDJFEYMUZIFTRQ-UHFFFAOYSA-N [4-[7-[[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=CC(F)=CC=3)=CC=C2C1=O NDJFEYMUZIFTRQ-UHFFFAOYSA-N 0.000 claims 1
• PVGOVCAOHGZDEF-UHFFFAOYSA-N [4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]phenyl] propanoate Chemical compound C1=CC(OC(=O)CC)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 PVGOVCAOHGZDEF-UHFFFAOYSA-N 0.000 claims 1
• VIICMKGBRBRXRG-UHFFFAOYSA-N [4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 VIICMKGBRBRXRG-UHFFFAOYSA-N 0.000 claims 1
• JSCZRVMYXMJBAJ-UHFFFAOYSA-N methyl 3-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2C(C3=CC=C(OCC4=C(N=C(S4)C=4C=CC(=CC=4)C(F)(F)F)C)C=C3OC=2)=O)=C1 JSCZRVMYXMJBAJ-UHFFFAOYSA-N 0.000 claims 1
• FIAYNGLPHFJWNL-UHFFFAOYSA-N methyl 3-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)=C1 FIAYNGLPHFJWNL-UHFFFAOYSA-N 0.000 claims 1
• LMJMMPUNPQYONN-UHFFFAOYSA-N methyl 3-[[3-(4-acetyloxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(OC(C)=O)=CC=4)=CO3)=O)=CC=2)=C1 LMJMMPUNPQYONN-UHFFFAOYSA-N 0.000 claims 1
• QMLJDJRQXXUTJD-UHFFFAOYSA-N methyl 3-[[3-[4-(2-amino-2-oxoethoxy)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(OCC(N)=O)=CC=4)=CO3)=O)=CC=2)=C1 QMLJDJRQXXUTJD-UHFFFAOYSA-N 0.000 claims 1
• KHPANTWQMRVIHT-UHFFFAOYSA-N methyl 3-[[3-[4-(n'-hydroxycarbamimidoyl)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)C(N)=NO)=CO3)=O)=CC=2)=C1 KHPANTWQMRVIHT-UHFFFAOYSA-N 0.000 claims 1
• FONJRTAJESCEPB-UHFFFAOYSA-N methyl 3-[[3-[4-[(4-methylphenyl)sulfonylamino]phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(=O)(=O)C=5C=CC(C)=CC=5)=CC=4)=CO3)=O)=CC=2)=C1 FONJRTAJESCEPB-UHFFFAOYSA-N 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• SZYSQGBOCVSYQS-UHFFFAOYSA-N n-(4-fluorophenyl)-4-[2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]piperazine-1-carbothioamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C(=S)NC=3C=CC(F)=CC=3)=CC=C2C1=O SZYSQGBOCVSYQS-UHFFFAOYSA-N 0.000 claims 1
• KDHZOCWAWMYCJB-UHFFFAOYSA-N n-[3-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)=C1 KDHZOCWAWMYCJB-UHFFFAOYSA-N 0.000 claims 1
• IYWMHWZYYBEMLX-UHFFFAOYSA-N n-[4-[4-oxo-7-[[2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl]methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3N=C(SC=3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O IYWMHWZYYBEMLX-UHFFFAOYSA-N 0.000 claims 1
• XRXFUBQZEAXFBU-UHFFFAOYSA-N n-[4-[4-oxo-7-[[3-(trifluoromethoxy)phenyl]methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(OC(F)(F)F)C=CC=3)=CC=C2C1=O XRXFUBQZEAXFBU-UHFFFAOYSA-N 0.000 claims 1
• DYOALZKAPRMVKL-UHFFFAOYSA-N n-[4-[4-oxo-7-[[3-(trifluoromethyl)phenyl]methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O DYOALZKAPRMVKL-UHFFFAOYSA-N 0.000 claims 1
• OZIYZNIPBGCGKS-UHFFFAOYSA-N n-[4-[7-[2-[3-[2-fluoro-4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-4-oxochromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCCC=3ON=C(N=3)C=3C(=CC(=CC=3)C(F)(F)F)F)=CC=C2C1=O OZIYZNIPBGCGKS-UHFFFAOYSA-N 0.000 claims 1
• NJYMIOGEDYKFQY-UHFFFAOYSA-N n-[4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)C=C1 NJYMIOGEDYKFQY-UHFFFAOYSA-N 0.000 claims 1
• TULOYQLETVYVIG-UHFFFAOYSA-N n-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)NCC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=C2C1=O TULOYQLETVYVIG-UHFFFAOYSA-N 0.000 claims 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 1
• 150000004866 oxadiazoles Chemical class 0.000 claims 1
• YLOBJVZLCAELSS-UHFFFAOYSA-N prop-2-enyl 3-[3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,2,4-oxadiazol-5-yl]benzoate Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(=O)OCC=C)=CC=C2C1=O YLOBJVZLCAELSS-UHFFFAOYSA-N 0.000 claims 1
• FJZJXFQFHMJTSI-UHFFFAOYSA-N prop-2-enyl 3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)OCC=C)=CC=C2C1=O FJZJXFQFHMJTSI-UHFFFAOYSA-N 0.000 claims 1
• PUASYUKPQVRYFH-UHFFFAOYSA-N propan-2-yl 3-[3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,2,4-oxadiazol-5-yl]benzoate Chemical compound CC(C)OC(=O)C1=CC=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)N=2)=C1 PUASYUKPQVRYFH-UHFFFAOYSA-N 0.000 claims 1
• JCGPLQJNELWBFZ-UHFFFAOYSA-N propan-2-yl 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CC(C)OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(N)=CC=4)=CO3)=O)=CC=2)=C1 JCGPLQJNELWBFZ-UHFFFAOYSA-N 0.000 claims 1
• QGUDVADPMYYATR-UHFFFAOYSA-N propan-2-yl 3-[[3-(4-carbamoylphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CC(C)OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)C(N)=O)=CO3)=O)=CC=2)=C1 QGUDVADPMYYATR-UHFFFAOYSA-N 0.000 claims 1
• OYNBZKPWLYYWMG-UHFFFAOYSA-N propan-2-yl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CC(C)OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(C)(=O)=O)=CC=4)=CO3)=O)=CC=2)=C1 OYNBZKPWLYYWMG-UHFFFAOYSA-N 0.000 claims 1
• 150000003222 pyridines Chemical class 0.000 claims 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 1
• 150000003557 thiazoles Chemical class 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 17
• 229940079593 drug Drugs 0.000 abstract description 13
• 150000002515 isoflavone derivatives Chemical class 0.000 abstract description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 abstract description 4
• 229930012930 isoflavone derivative Natural products 0.000 abstract description 2
• 229960005181 morphine Drugs 0.000 abstract description 2
• 230000005764 inhibitory process Effects 0.000 description 202
• 239000000203 mixture Substances 0.000 description 128
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
• 238000006243 chemical reaction Methods 0.000 description 84
• 238000002360 preparation method Methods 0.000 description 71
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 58
• 239000002904 solvent Substances 0.000 description 53
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 49
• 239000000243 solution Substances 0.000 description 49
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
• 235000019439 ethyl acetate Nutrition 0.000 description 44
• 230000002829 reductive effect Effects 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 38
• 238000005481 NMR spectroscopy Methods 0.000 description 30
• 241000700159 Rattus Species 0.000 description 30
• ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 30
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 29
• 239000000741 silica gel Substances 0.000 description 29
• 229910002027 silica gel Inorganic materials 0.000 description 29
• 229960001866 silicon dioxide Drugs 0.000 description 29
• 239000004480 active ingredient Substances 0.000 description 27
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
• 239000007787 solid Substances 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 22
• 125000004181 carboxyalkyl group Chemical group 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 150000001412 amines Chemical class 0.000 description 21
• 239000000047 product Substances 0.000 description 21
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 230000000694 effects Effects 0.000 description 19
• 239000004615 ingredient Substances 0.000 description 19
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• 239000003826 tablet Substances 0.000 description 19
• 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 18
• 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• 125000000392 cycloalkenyl group Chemical group 0.000 description 17
• 239000012442 inert solvent Substances 0.000 description 16
• 241001465754 Metazoa Species 0.000 description 15
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 235000013305 food Nutrition 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 239000002585 base Substances 0.000 description 13
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 150000003839 salts Chemical class 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 125000005843 halogen group Chemical group 0.000 description 11
• TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical group Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 125000000547 substituted alkyl group Chemical group 0.000 description 11
• 125000004414 alkyl thio group Chemical group 0.000 description 10
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 10
• 239000007924 injection Substances 0.000 description 10
• 238000002347 injection Methods 0.000 description 10
• 238000012549 training Methods 0.000 description 10
• 239000005711 Benzoic acid Substances 0.000 description 9
• 229930194542 Keto Natural products 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
• 238000004440 column chromatography Methods 0.000 description 9
• 235000007240 daidzein Nutrition 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 description 9
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• 150000003573 thiols Chemical class 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 125000000033 alkoxyamino group Chemical group 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
• 239000007864 aqueous solution Substances 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 239000000706 filtrate 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
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 230000002787 reinforcement Effects 0.000 description 8
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 7
• GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 description 7
• KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 description 7
• 102000010909 Monoamine Oxidase Human genes 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 230000008033 biological extinction Effects 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000012230 colorless oil Substances 0.000 description 7
• KYQZWONCHDNPDP-QNDFHXLGSA-N daidzein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-QNDFHXLGSA-N 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 238000001802 infusion Methods 0.000 description 7
• 238000001953 recrystallisation Methods 0.000 description 7
• 238000010898 silica gel chromatography Methods 0.000 description 7
• 238000012384 transportation and delivery Methods 0.000 description 7
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
• 239000008188 pellet Substances 0.000 description 6
• 238000012746 preparative thin layer chromatography Methods 0.000 description 6
• 235000019698 starch Nutrition 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• 208000007848 Alcoholism Diseases 0.000 description 5
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
• 241000208125 Nicotiana Species 0.000 description 5
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 5
• 235000008696 isoflavones Nutrition 0.000 description 5
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
• 239000008108 microcrystalline cellulose Substances 0.000 description 5
• 229940016286 microcrystalline cellulose Drugs 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 238000003825 pressing Methods 0.000 description 5
• 230000037452 priming Effects 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 229930195734 saturated hydrocarbon Natural products 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 208000011117 substance-related disease Diseases 0.000 description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
• 125000003107 substituted aryl group Chemical group 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• OBFAPCIUSYHFIE-UHFFFAOYSA-N (5-hydroxyindol-3-yl)acetaldehyde Chemical compound OC1=CC=C2NC=C(CC=O)C2=C1 OBFAPCIUSYHFIE-UHFFFAOYSA-N 0.000 description 4
• NARVIWMVBMUEOG-UHFFFAOYSA-N 2-Hydroxy-propylene Natural products CC(O)=C NARVIWMVBMUEOG-UHFFFAOYSA-N 0.000 description 4
• YBSGKKITPLSUPH-HXUWFJFHSA-N 3-(4-hydroxyphenyl)-7-[(2r)-2-hydroxy-3-[[3-(trifluoromethyl)phenyl]methylamino]propoxy]chromen-4-one Chemical compound C([C@@H](O)COC=1C=C2C(C(C(C=3C=CC(O)=CC=3)=CO2)=O)=CC=1)NCC1=CC=CC(C(F)(F)F)=C1 YBSGKKITPLSUPH-HXUWFJFHSA-N 0.000 description 4
• INANILNLXTUPHD-UHFFFAOYSA-N 3-(chloromethyl)-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2ON=C(CCl)N=2)=C1 INANILNLXTUPHD-UHFFFAOYSA-N 0.000 description 4
• GIWPLJABJPALKR-UHFFFAOYSA-N 3-(dimethylamino)-1-(2-hydroxy-4-methoxyphenyl)prop-2-en-1-one Chemical compound COC1=CC=C(C(=O)C=CN(C)C)C(O)=C1 GIWPLJABJPALKR-UHFFFAOYSA-N 0.000 description 4
• CZHDFFKLUHEVAQ-UHFFFAOYSA-N 4-(chloromethyl)-2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazole Chemical compound FC(F)(F)C1=CC(F)=CC(C=2OC=C(CCl)N=2)=C1 CZHDFFKLUHEVAQ-UHFFFAOYSA-N 0.000 description 4
• BHESGBIBNPDUJW-HXUWFJFHSA-N 7-[(2r)-3-[(3,5-difluorophenyl)methylamino]-2-hydroxypropoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C([C@@H](O)COC=1C=C2C(C(C(C=3C=CC(O)=CC=3)=CO2)=O)=CC=1)NCC1=CC(F)=CC(F)=C1 BHESGBIBNPDUJW-HXUWFJFHSA-N 0.000 description 4
• VLNVZSXVAGSIHK-UHFFFAOYSA-N 7-hydroxy-3-iodochromen-4-one Chemical compound O1C=C(I)C(=O)C=2C1=CC(O)=CC=2 VLNVZSXVAGSIHK-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
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• 235000010233 benzoic acid Nutrition 0.000 description 4
• 125000001246 bromo group Chemical group Br* 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 4
• OLYHXOQSRWBKPN-UHFFFAOYSA-N ditert-butyl [4-[7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-4-oxochromen-3-yl]phenoxy]methyl phosphate Chemical compound C1=CC(OCOP(=O)(OC(C)(C)C)OC(C)(C)C)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O OLYHXOQSRWBKPN-UHFFFAOYSA-N 0.000 description 4
• LNJAJHJFSKUCIR-UHFFFAOYSA-N ditert-butyl chloromethyl phosphate Chemical compound CC(C)(C)OP(=O)(OCCl)OC(C)(C)C LNJAJHJFSKUCIR-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 206010013663 drug dependence Diseases 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 238000007912 intraperitoneal administration Methods 0.000 description 4
• 238000001990 intravenous administration Methods 0.000 description 4
• 125000002346 iodo group Chemical group I* 0.000 description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• IIMPDNKAFMXDQT-UHFFFAOYSA-N n-[4-[4-oxo-7-[[2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]chromen-3-yl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3SC(=NC=3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O IIMPDNKAFMXDQT-UHFFFAOYSA-N 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 3
• WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 description 3
• SHGLJXBLXNNCTE-UHFFFAOYSA-N 2-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=CC=CC=C2O1 SHGLJXBLXNNCTE-UHFFFAOYSA-N 0.000 description 3
• OOZFVAKRVNCKET-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2-(trifluoromethyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=C(C(F)(F)F)OC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O OOZFVAKRVNCKET-UHFFFAOYSA-N 0.000 description 3
• DUAXQHUFMGCKGX-UHFFFAOYSA-N 3-(4-methoxyphenyl)-7-(oxiran-2-ylmethoxy)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC3OC3)=CC=C2C1=O DUAXQHUFMGCKGX-UHFFFAOYSA-N 0.000 description 3
• IHHWIRIIIZBIDV-UHFFFAOYSA-N 4,5-dihydroxy-3-phenylchromen-2-one Chemical compound OC=1C=2C(O)=CC=CC=2OC(=O)C=1C1=CC=CC=C1 IHHWIRIIIZBIDV-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 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 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• 206010013654 Drug abuse Diseases 0.000 description 3
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
• 239000005977 Ethylene Substances 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 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 3
• 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 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• QWWZNBCIOKYBNE-UHFFFAOYSA-N OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)[N+]([O-])=O)=CO3)=O)=CC=2)=C1 Chemical compound OC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)[N+]([O-])=O)=CO3)=O)=CC=2)=C1 QWWZNBCIOKYBNE-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
• 101710171573 Primary amine oxidase Proteins 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• 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 3
• 229930006000 Sucrose Natural products 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 206010001584 alcohol abuse Diseases 0.000 description 3
• 208000025746 alcohol use disease Diseases 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000003125 aqueous solvent Substances 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 125000002837 carbocyclic group Chemical group 0.000 description 3
• 125000005518 carboxamido group Chemical group 0.000 description 3
• 150000007942 carboxylates Chemical class 0.000 description 3
• 235000019504 cigarettes Nutrition 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
• 238000000576 coating method Methods 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 235000005687 corn oil Nutrition 0.000 description 3
• 239000002285 corn oil Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 230000034994 death Effects 0.000 description 3
• 231100000517 death Toxicity 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• RGOYQVUKPGSMRP-UHFFFAOYSA-N ditert-butyl [4-[7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-4-oxochromen-3-yl]phenyl] phosphite Chemical compound C1=CC(OP(OC(C)(C)C)OC(C)(C)C)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O RGOYQVUKPGSMRP-UHFFFAOYSA-N 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 125000004475 heteroaralkyl group Chemical group 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 210000004731 jugular vein Anatomy 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 125000005647 linker group Chemical group 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 description 3
• 229960002525 mecamylamine Drugs 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• MUWNYJYVZLIGNK-UHFFFAOYSA-N n'-[3-fluoro-5-(trifluoromethyl)phenyl]-n-hydroxymethanimidamide Chemical compound ONC=NC1=CC(F)=CC(C(F)(F)F)=C1 MUWNYJYVZLIGNK-UHFFFAOYSA-N 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
• 239000003586 protic polar solvent Substances 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 238000011084 recovery Methods 0.000 description 3
• 230000000391 smoking effect Effects 0.000 description 3
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
• WOBNYPYYJSLSSI-YFKPBYRVSA-N (1s)-1-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethanol Chemical compound O1C([C@@H](O)C)=NC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 WOBNYPYYJSLSSI-YFKPBYRVSA-N 0.000 description 2
• 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 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 2
• CLBVGVJSNFQCOG-UHFFFAOYSA-N 1-(2-chloroethyl)-4-(4-methoxyphenyl)piperazine Chemical compound C1=CC(OC)=CC=C1N1CCN(CCCl)CC1 CLBVGVJSNFQCOG-UHFFFAOYSA-N 0.000 description 2
• IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• NNJIPLNZQWTZBZ-UHFFFAOYSA-N 2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyacetonitrile Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC#N)=CC=C2C1=O NNJIPLNZQWTZBZ-UHFFFAOYSA-N 0.000 description 2
• DHGSSFOTSSOFLK-UHFFFAOYSA-N 2-[3-fluoro-5-(trifluoromethyl)phenyl]-4-(3-iodopropyl)-1,3-oxazole Chemical compound FC(F)(F)C1=CC(F)=CC(C=2OC=C(CCCI)N=2)=C1 DHGSSFOTSSOFLK-UHFFFAOYSA-N 0.000 description 2
• NSXHBSIIXXOEJZ-UHFFFAOYSA-N 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,3-oxazole-5-carboxylic acid Chemical compound O1C(C(=O)O)=CN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 NSXHBSIIXXOEJZ-UHFFFAOYSA-N 0.000 description 2
• ZJFWCELATJMDNO-UHFFFAOYSA-N 2-bromo-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CBr)C=C1 ZJFWCELATJMDNO-UHFFFAOYSA-N 0.000 description 2
• NPEIUNVTLXEOLT-UHFFFAOYSA-N 2-chloro-1,1,1-trimethoxyethane Chemical compound COC(CCl)(OC)OC NPEIUNVTLXEOLT-UHFFFAOYSA-N 0.000 description 2
• MOEJRZLPQODXGM-UHFFFAOYSA-N 2-chloro-n-[3-(trifluoromethyl)phenyl]acetamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)CCl)=C1 MOEJRZLPQODXGM-UHFFFAOYSA-N 0.000 description 2
• VIUAWBLQYVJXIW-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-(2-hydroxy-3-phenylpropoxy)chromen-4-one Chemical compound C=1C=CC=CC=1CC(O)COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 VIUAWBLQYVJXIW-UHFFFAOYSA-N 0.000 description 2
• AFPWFAXOBKZWFY-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[(2-phenyl-1,3-oxazol-5-yl)methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3OC(=NC=3)C=3C=CC=CC=3)=CC=C2C1=O AFPWFAXOBKZWFY-UHFFFAOYSA-N 0.000 description 2
• VIUAWBLQYVJXIW-LJQANCHMSA-N 3-(4-hydroxyphenyl)-7-[(2r)-2-hydroxy-3-phenylpropoxy]chromen-4-one Chemical compound C([C@H](O)CC=1C=CC=CC=1)OC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 VIUAWBLQYVJXIW-LJQANCHMSA-N 0.000 description 2
• YBSGKKITPLSUPH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[2-hydroxy-3-[[3-(trifluoromethyl)phenyl]methylamino]propoxy]chromen-4-one Chemical compound C=1C=C(C(C(C=2C=CC(O)=CC=2)=CO2)=O)C2=CC=1OCC(O)CNCC1=CC=CC(C(F)(F)F)=C1 YBSGKKITPLSUPH-UHFFFAOYSA-N 0.000 description 2
• KVLGZHXMDKNCSJ-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3SC(=NC=3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O KVLGZHXMDKNCSJ-UHFFFAOYSA-N 0.000 description 2
• MBMNXJFJLQOHHD-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[4-methoxy-3-(trifluoromethyl)phenyl]methoxy]chromen-4-one Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 MBMNXJFJLQOHHD-UHFFFAOYSA-N 0.000 description 2
• ARNSQJHBXOIXRH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound COC1=CC=CC=C1C1=NC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=CO3)=O)=CC=2)=NO1 ARNSQJHBXOIXRH-UHFFFAOYSA-N 0.000 description 2
• JDRLUTQDZBMYTM-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-(trifluoromethyl)pyridin-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=NC=3)C(F)(F)F)=CC=C2C1=O JDRLUTQDZBMYTM-UHFFFAOYSA-N 0.000 description 2
• NQDAOPURZCUSBU-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=CC(=CC=3)C(F)(F)F)=CC=C2C1=O NQDAOPURZCUSBU-UHFFFAOYSA-N 0.000 description 2
• OJXXFCIHGREHIH-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[5-[4-methoxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-2-(trifluoromethyl)chromen-4-one Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C1=NC(COC=2C=C3C(C(C(C=4C=CC(O)=CC=4)=C(O3)C(F)(F)F)=O)=CC=2)=NO1 OJXXFCIHGREHIH-UHFFFAOYSA-N 0.000 description 2
• BJDQPQWMJZEAPE-UHFFFAOYSA-N 3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC=CC=C2C1=O BJDQPQWMJZEAPE-UHFFFAOYSA-N 0.000 description 2
• HUMHXLIXFLWZNP-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]chromen-4-one Chemical compound C1=NC(OC)=CC=C1C1=COC2=CC(OCC3=C(N=C(S3)C=3C=CC(=CC=3)C(F)(F)F)C)=CC=C2C1=O HUMHXLIXFLWZNP-UHFFFAOYSA-N 0.000 description 2
• KAHNJRAGQDDUMW-UHFFFAOYSA-N 3-[2,4-bis[(2-methylpropan-2-yl)oxy]pyrimidin-5-yl]-7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound CC(C)(C)OC1=NC(OC(C)(C)C)=NC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O KAHNJRAGQDDUMW-UHFFFAOYSA-N 0.000 description 2
• HXUZZDRBZVNJPN-UHFFFAOYSA-N 3-iodo-7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]chromen-4-one Chemical compound S1C(COC=2C=C3C(C(C(I)=CO3)=O)=CC=2)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 HXUZZDRBZVNJPN-UHFFFAOYSA-N 0.000 description 2
• RAMRIHLZEAHUBU-UHFFFAOYSA-N 3-iodo-7-methoxychromen-4-one Chemical compound O1C=C(I)C(=O)C=2C1=CC(OC)=CC=2 RAMRIHLZEAHUBU-UHFFFAOYSA-N 0.000 description 2
• VZMYKSGRMWHSTC-UHFFFAOYSA-N 4-[4-oxo-7-[[3-[3-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]methoxy]chromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC=CC(C2=NOC(COC=3C=C4C(C(C(C=5C=CC(=CC=5)C#N)=CO4)=O)=CC=3)=C2)=C1 VZMYKSGRMWHSTC-UHFFFAOYSA-N 0.000 description 2
• KOLUIURKEYSMOR-UHFFFAOYSA-N 4-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]benzonitrile Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(C#N)C=C1 KOLUIURKEYSMOR-UHFFFAOYSA-N 0.000 description 2
• QYVQTNWRQXUXJF-UHFFFAOYSA-N 4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-yl]methoxy]-4-oxochromen-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC(F)=CC(C=2OC(COC=3C=C4C(C(C(C=5C=CC(=CC=5)C#N)=CO4)=O)=CC=3)=NN=2)=C1 QYVQTNWRQXUXJF-UHFFFAOYSA-N 0.000 description 2
• FINMWZYOOYZFFV-UHFFFAOYSA-N 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-7-methoxychromen-2-one Chemical compound C=1C(=O)OC2=CC(OC)=CC=C2C=1COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 FINMWZYOOYZFFV-UHFFFAOYSA-N 0.000 description 2
• YHAORQQIHFPGRQ-UHFFFAOYSA-N 5-[4-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]phenyl]-1,3-diazinane-2,4-dione Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(=CC=5)C5C(NC(=O)NC5)=O)=CO4)=O)=CC=3)N=2)=C1 YHAORQQIHFPGRQ-UHFFFAOYSA-N 0.000 description 2
• LIMLEVSJNWTFGC-UHFFFAOYSA-N 5-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]-1h-pyrimidine-2,4-dione Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C(NC(=O)NC=5)=O)=CO4)=O)=CC=3)N=2)=C1 LIMLEVSJNWTFGC-UHFFFAOYSA-N 0.000 description 2
• DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 2
• HALZFZWMHAVEKJ-UHFFFAOYSA-N 7-(pyridin-2-ylmethoxy)-3-[4-(pyridin-2-ylmethoxy)phenyl]chromen-4-one Chemical compound C=1C=C2C(=O)C(C=3C=CC(OCC=4N=CC=CC=4)=CC=3)=COC2=CC=1OCC1=CC=CC=N1 HALZFZWMHAVEKJ-UHFFFAOYSA-N 0.000 description 2
• GBPXKSUYGHTFAK-UHFFFAOYSA-N 7-[2-[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-5-yl]ethoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCC=3OC(=NC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O GBPXKSUYGHTFAK-UHFFFAOYSA-N 0.000 description 2
• RPQZKJITPGRCKF-UHFFFAOYSA-N 7-[2-hydroxy-3-[[3-(trifluoromethyl)phenyl]methylamino]propoxy]-3-(4-methoxyphenyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC(O)CNCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O RPQZKJITPGRCKF-UHFFFAOYSA-N 0.000 description 2
• BHESGBIBNPDUJW-UHFFFAOYSA-N 7-[3-[(3,5-difluorophenyl)methylamino]-2-hydroxypropoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C=1C=C(C(C(C=2C=CC(O)=CC=2)=CO2)=O)C2=CC=1OCC(O)CNCC1=CC(F)=CC(F)=C1 BHESGBIBNPDUJW-UHFFFAOYSA-N 0.000 description 2
• VNNSFXKBYWVKED-UHFFFAOYSA-N 7-[3-[4-(4-chlorophenyl)-1h-pyrazol-5-yl]propoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCCC=3C(=CNN=3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O VNNSFXKBYWVKED-UHFFFAOYSA-N 0.000 description 2
• XKTXUAMEECZDAD-MRXNPFEDSA-N 7-[3-[[(1r)-1-(4-fluorophenyl)ethyl]amino]-2-oxopropoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)CC(=O)COC(C=1)=CC=C(C2=O)C=1OC=C2C1=CC=C(O)C=C1 XKTXUAMEECZDAD-MRXNPFEDSA-N 0.000 description 2
• JEDBDCQTOPSONA-UHFFFAOYSA-N 7-[[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3ON=C(N=3)C=3C=CC(Cl)=CC=3)=CC=C2C1=O JEDBDCQTOPSONA-UHFFFAOYSA-N 0.000 description 2
• YQJGDFSWAKPWKP-UHFFFAOYSA-N 7-[[5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3SC(=NN=3)C=3C(=CC=CC=3)Cl)=CC=C2C1=O YQJGDFSWAKPWKP-UHFFFAOYSA-N 0.000 description 2
• OHLICEDYIMGQJJ-UHFFFAOYSA-N 7-[[5-(3-aminophenyl)-1,3,4-oxadiazol-2-yl]methoxy]-3-(4-hydroxyphenyl)chromen-4-one Chemical compound NC1=CC=CC(C=2OC(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)=NN=2)=C1 OHLICEDYIMGQJJ-UHFFFAOYSA-N 0.000 description 2
• ARGNGSMWKBQUHD-UHFFFAOYSA-N 7-[[5-(trifluoromethyl)pyridin-3-yl]methoxy]-3-[4-[[6-(trifluoromethyl)pyridin-3-yl]methoxy]phenyl]chromen-4-one Chemical compound FC(F)(F)C1=CN=CC(COC=2C=C3C(C(C(C=4C=CC(OCC=5C=NC(=CC=5)C(F)(F)F)=CC=4)=CO3)=O)=CC=2)=C1 ARGNGSMWKBQUHD-UHFFFAOYSA-N 0.000 description 2
• QYQKUUSGCMRSCO-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(1h-indazol-5-yl)chromen-4-one Chemical compound FC(F)(F)C1=CC(F)=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=C6C=NNC6=CC=5)=CO4)=O)=CC=3)N=2)=C1 QYQKUUSGCMRSCO-UHFFFAOYSA-N 0.000 description 2
• DZXXEBYBFAWEGV-UHFFFAOYSA-N 7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-3-(4-hydroxyphenyl)-2-(trifluoromethyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=C(C(F)(F)F)OC2=CC(OCC=3N=C(ON=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O DZXXEBYBFAWEGV-UHFFFAOYSA-N 0.000 description 2
• LHFWZVAHDFOEGQ-UHFFFAOYSA-N 7-[[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl]methoxy]-3-(4-morpholin-4-ylphenyl)chromen-4-one Chemical compound CC=1SC(C=2C=CC(=CC=2)C(F)(F)F)=NC=1COC(C=1)=CC=C(C2=O)C=1OC=C2C(C=C1)=CC=C1N1CCOCC1 LHFWZVAHDFOEGQ-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
• OMUQGLOXIJKKRV-UHFFFAOYSA-N C1=CC(NS(=O)(=O)C)=CC=C1C1=C(O)OC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=C(O)OC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O OMUQGLOXIJKKRV-UHFFFAOYSA-N 0.000 description 2
• 208000022497 Cocaine-Related disease Diseases 0.000 description 2
• 206010010144 Completed suicide Diseases 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 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
• 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 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 229910003813 NRa Inorganic materials 0.000 description 2
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-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 compound 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
• QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-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
• 241000700157 Rattus norvegicus Species 0.000 description 2
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DJKKTRTXRZJYHE-LURJTMIESA-N [(1s)-1-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethyl] acetate Chemical compound O1C([C@@H](OC(C)=O)C)=NC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 DJKKTRTXRZJYHE-LURJTMIESA-N 0.000 description 2
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 2
• YKNZTUQUXUXTLE-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=CC(C(F)(F)F)=C1 YKNZTUQUXUXTLE-UHFFFAOYSA-N 0.000 description 2
• NKVPHNQRMOEKOW-UHFFFAOYSA-N [5-[3-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methanol Chemical compound O1N=C(CO)C=C1C1=CC=CC(C(F)(F)F)=C1 NKVPHNQRMOEKOW-UHFFFAOYSA-N 0.000 description 2
• QHQYPCJDXVXVLU-LURJTMIESA-N [[amino-[3-fluoro-5-(trifluoromethyl)phenyl]methylidene]amino] (2s)-2-acetyloxypropanoate Chemical compound CC(=O)O[C@@H](C)C(=O)ON=C(N)C1=CC(F)=CC(C(F)(F)F)=C1 QHQYPCJDXVXVLU-LURJTMIESA-N 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
• 201000007930 alcohol dependence Diseases 0.000 description 2
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000000844 anti-bacterial effect Effects 0.000 description 2
• 239000000935 antidepressant agent Substances 0.000 description 2
• 229940005513 antidepressants Drugs 0.000 description 2
• 239000003429 antifungal agent Substances 0.000 description 2
• 229940121375 antifungal agent Drugs 0.000 description 2
• 239000002220 antihypertensive agent Substances 0.000 description 2
• 229940127088 antihypertensive drug Drugs 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000000732 arylene group Chemical group 0.000 description 2
• 230000002238 attenuated effect Effects 0.000 description 2
• 238000013542 behavioral therapy Methods 0.000 description 2
• 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 2
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
• 230000023555 blood coagulation Effects 0.000 description 2
• 229940028978 brevital Drugs 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 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
• 229910052799 carbon Inorganic materials 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 235000019788 craving Nutrition 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 229960002069 diamorphine Drugs 0.000 description 2
• JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 2
• 125000004212 difluorophenyl group Chemical group 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000002612 dispersion medium Substances 0.000 description 2
• 229960002563 disulfiram Drugs 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• UXOLDCOJRAMLTQ-UTCJRWHESA-N ethyl (2z)-2-chloro-2-hydroxyiminoacetate Chemical compound CCOC(=O)C(\Cl)=N\O UXOLDCOJRAMLTQ-UTCJRWHESA-N 0.000 description 2
• AUJZBVANIBYYEO-UHFFFAOYSA-N ethyl 2-[4-[7-(2-ethoxy-2-oxoethoxy)-4-oxochromen-3-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1C1=COC2=CC(OCC(=O)OCC)=CC=C2C1=O AUJZBVANIBYYEO-UHFFFAOYSA-N 0.000 description 2
• BTXVLNBPXHOOHF-UHFFFAOYSA-N ethyl 3-[7-[2-[3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]ethoxy]-4-oxochromen-3-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2C(C3=CC=C(OCCC=4ON=C(N=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)=C1 BTXVLNBPXHOOHF-UHFFFAOYSA-N 0.000 description 2
• DUCFOVKQSYCHJF-UHFFFAOYSA-N ethyl 3-[7-[[5-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]-4-oxochromen-3-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2C(C3=CC=C(OCC=4N=C(ON=4)C=4C=C(C=C(F)C=4)C(F)(F)F)C=C3OC=2)=O)=C1 DUCFOVKQSYCHJF-UHFFFAOYSA-N 0.000 description 2
• HWZHNWHEZHACDC-UHFFFAOYSA-N ethyl 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 HWZHNWHEZHACDC-UHFFFAOYSA-N 0.000 description 2
• XKCHYHLRNPHDPD-UHFFFAOYSA-N ethyl 5-[3-(trifluoromethyl)phenyl]-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC=CC(C(F)(F)F)=C1 XKCHYHLRNPHDPD-UHFFFAOYSA-N 0.000 description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 235000012631 food intake Nutrition 0.000 description 2
• 230000037406 food intake Effects 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 230000005802 health problem Effects 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• KDXZREBVGAGZHS-UHFFFAOYSA-M methohexital sodium Chemical compound [Na+].CCC#CC(C)C1(CC=C)C(=O)N=C([O-])N(C)C1=O KDXZREBVGAGZHS-UHFFFAOYSA-M 0.000 description 2
• UXSGCFFGBFFORL-UHFFFAOYSA-N methyl 2-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,3-oxazole-5-carboxylate Chemical compound O1C(C(=O)OC)=CN=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 UXSGCFFGBFFORL-UHFFFAOYSA-N 0.000 description 2
• LMOZMPGENBWCAB-UHFFFAOYSA-N methyl 3-[[3-(4-acetamidophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NC(C)=O)=CC=4)=CO3)=O)=CC=2)=C1 LMOZMPGENBWCAB-UHFFFAOYSA-N 0.000 description 2
• MUHKRTNJUKNLPC-UHFFFAOYSA-N methyl 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(N)=CC=4)=CO3)=O)=CC=2)=C1 MUHKRTNJUKNLPC-UHFFFAOYSA-N 0.000 description 2
• OMKBODRLWIFODE-UHFFFAOYSA-N methyl 3-[[3-(4-nitrophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(=CC=4)[N+]([O-])=O)=CO3)=O)=CC=2)=C1 OMKBODRLWIFODE-UHFFFAOYSA-N 0.000 description 2
• GSIQUMXPJGHBIC-UHFFFAOYSA-N methyl 3-[[3-(6-methoxypyridin-3-yl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound COC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=NC(OC)=CC=4)=CO3)=O)=CC=2)=C1 GSIQUMXPJGHBIC-UHFFFAOYSA-N 0.000 description 2
• LRKQQFFOJDWCTL-UHFFFAOYSA-N methyl 3-[[3-[4-[(z)-n'-methoxycarbamimidoyl]phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(C(/N)=N/OC)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)OC)=CC=C2C1=O LRKQQFFOJDWCTL-UHFFFAOYSA-N 0.000 description 2
• VCTHVPYOPIHBNP-UHFFFAOYSA-N methyl 4-[7-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]-4-oxochromen-3-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=COC2=CC(OCC3=C(N=C(S3)C=3C=CC(=CC=3)C(F)(F)F)C)=CC=C2C1=O VCTHVPYOPIHBNP-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• DABNYYYHTLVHIY-UHFFFAOYSA-N n-(3-fluorophenyl)-4-[2-[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]piperazine-1-carbothioamide Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCCN3CCN(CC3)C(=S)NC=3C=C(F)C=CC=3)=CC=C2C1=O DABNYYYHTLVHIY-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
• 230000000926 neurological effect Effects 0.000 description 2
• 238000002670 nicotine replacement therapy Methods 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000013641 positive control Substances 0.000 description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
• 239000004299 sodium benzoate Substances 0.000 description 2
• 235000010234 sodium benzoate Nutrition 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 239000008247 solid mixture Substances 0.000 description 2
• 239000008223 sterile water Substances 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 201000009032 substance abuse Diseases 0.000 description 2
• 125000005156 substituted alkylene group Chemical group 0.000 description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 description 2
• 150000003457 sulfones Chemical class 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 150000003462 sulfoxides Chemical class 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 229940027257 timentin Drugs 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 239000000230 xanthan gum Substances 0.000 description 2
• 235000010493 xanthan gum Nutrition 0.000 description 2
• 229920001285 xanthan gum Polymers 0.000 description 2
• 229940082509 xanthan gum Drugs 0.000 description 2
• SCMHTXQHAHWVSX-BNTLRKBRSA-L (1r,2r)-cyclohexane-1,2-diamine;[hydroxy(oxido)phosphoryl] hydrogen phosphate;platinum(2+) Chemical compound [Pt+2].N[C@@H]1CCCC[C@H]1N.OP([O-])(=O)OP(O)([O-])=O SCMHTXQHAHWVSX-BNTLRKBRSA-L 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• VJNGGOMRUHYAMC-UHFFFAOYSA-N (3,5-difluorophenyl)methanamine Chemical compound NCC1=CC(F)=CC(F)=C1 VJNGGOMRUHYAMC-UHFFFAOYSA-N 0.000 description 1
• CCIDRWOYZRKAPP-UHFFFAOYSA-N (5-pyridin-2-yl-1,2-oxazol-3-yl)methanol Chemical compound O1N=C(CO)C=C1C1=CC=CC=N1 CCIDRWOYZRKAPP-UHFFFAOYSA-N 0.000 description 1
• DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-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
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 1
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
• YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• 150000005072 1,3,4-oxadiazoles Chemical class 0.000 description 1
• MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound 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
• GQNHARINTUWVGG-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound [CH2]COCCOCCOCC GQNHARINTUWVGG-UHFFFAOYSA-N 0.000 description 1
• PAHXLHWOHJTWRU-UHFFFAOYSA-N 1-ethynyl-3-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=CC(C#C)=C1 PAHXLHWOHJTWRU-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
• IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 1
• JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-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
• JEQDSBVHLKBEIZ-UHFFFAOYSA-N 2-chloropropanoyl chloride Chemical compound CC(Cl)C(Cl)=O JEQDSBVHLKBEIZ-UHFFFAOYSA-N 0.000 description 1
• AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-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
• KOYURRCJKKYZAM-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[3-(5h-tetrazol-5-yl)phenyl]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C3N=NN=N3)=CC=C2C1=O KOYURRCJKKYZAM-UHFFFAOYSA-N 0.000 description 1
• OETXYXJPMCXLGD-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-7-[[[3-(trifluoromethyl)phenyl]methylamino]methoxy]chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCNCC=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O OETXYXJPMCXLGD-UHFFFAOYSA-N 0.000 description 1
• WWCAXINXYQUHRB-UHFFFAOYSA-N 3-(4-nitrophenyl)-7-[[5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]methoxy]chromen-4-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=COC2=CC(OCC=3N=C(ON=3)C=3C=C(C=CC=3)C(F)(F)F)=CC=C2C1=O WWCAXINXYQUHRB-UHFFFAOYSA-N 0.000 description 1
• LZUJIYKWHAFVOU-UHFFFAOYSA-N 3-(bromomethyl)-5-[3-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound FC(F)(F)C1=CC=CC(C=2ON=C(CBr)C=2)=C1 LZUJIYKWHAFVOU-UHFFFAOYSA-N 0.000 description 1
• AHEIVQPKJWJKHI-UHFFFAOYSA-N 3-(chloromethyl)-5-pyridin-2-yl-1,2-oxazole Chemical compound O1N=C(CCl)C=C1C1=CC=CC=N1 AHEIVQPKJWJKHI-UHFFFAOYSA-N 0.000 description 1
• RYKRFJNIOMBDME-UHFFFAOYSA-N 3-[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]propan-1-ol Chemical compound OCCCC1=COC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 RYKRFJNIOMBDME-UHFFFAOYSA-N 0.000 description 1
• XOLUYQBCMVOQKQ-UHFFFAOYSA-N 3-[[3-(4-nitrophenyl)-4-oxochromen-7-yl]oxymethyl]benzonitrile Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C#N)=CC=C2C1=O XOLUYQBCMVOQKQ-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• AYNUKEDZAYOEGG-UHFFFAOYSA-N 3-fluoro-5-(trifluoromethyl)benzonitrile Chemical compound FC1=CC(C#N)=CC(C(F)(F)F)=C1 AYNUKEDZAYOEGG-UHFFFAOYSA-N 0.000 description 1
• XKPXZZKHNBQQDD-UHFFFAOYSA-N 3-iodo-7-methoxychromen-2-one Chemical compound C1=C(I)C(=O)OC2=CC(OC)=CC=C21 XKPXZZKHNBQQDD-UHFFFAOYSA-N 0.000 description 1
• JJBDWBUEPCGFMN-UHFFFAOYSA-N 3-phenyl-1,2,4-oxadiazole Chemical compound O1C=NC(C=2C=CC=CC=2)=N1 JJBDWBUEPCGFMN-UHFFFAOYSA-N 0.000 description 1
• NJACFYHMOFEZDU-UHFFFAOYSA-N 3-prop-2-enylbenzoic acid Chemical compound OC(=O)C1=CC=CC(CC=C)=C1 NJACFYHMOFEZDU-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• QKTDAHTUDNNSPD-UHFFFAOYSA-N 4-(chloromethyl)-2-(3,4,5-trifluorophenyl)-1,3-oxazole Chemical compound FC1=C(F)C(F)=CC(C=2OC=C(CCl)N=2)=C1 QKTDAHTUDNNSPD-UHFFFAOYSA-N 0.000 description 1
• RHRWTBORHGIPTG-UHFFFAOYSA-N 4-(chloromethyl)-2-(3,4-difluorophenyl)-1,3-oxazole Chemical compound C1=C(F)C(F)=CC=C1C1=NC(CCl)=CO1 RHRWTBORHGIPTG-UHFFFAOYSA-N 0.000 description 1
• SZWXXPNCHFFMNS-UHFFFAOYSA-N 4-(chloromethyl)-2-(3,5-difluorophenyl)-1,3-oxazole Chemical compound FC1=CC(F)=CC(C=2OC=C(CCl)N=2)=C1 SZWXXPNCHFFMNS-UHFFFAOYSA-N 0.000 description 1
• BGGPUCCJQGIJRL-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-chlorophenyl)-1,3-oxazole Chemical compound ClCC1=COC(C=2C=CC(Cl)=CC=2)=N1 BGGPUCCJQGIJRL-UHFFFAOYSA-N 0.000 description 1
• GVPZSTFLDSJXRT-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-fluorophenyl)-1,3-oxazole Chemical compound C1=CC(F)=CC=C1C1=NC(CCl)=CO1 GVPZSTFLDSJXRT-UHFFFAOYSA-N 0.000 description 1
• FERDGQKDQQQEEI-UHFFFAOYSA-N 4-(chloromethyl)-2-[3-(trifluoromethyl)phenyl]-1,3-oxazole Chemical compound FC(F)(F)C1=CC=CC(C=2OC=C(CCl)N=2)=C1 FERDGQKDQQQEEI-UHFFFAOYSA-N 0.000 description 1
• ANSKJZIDWXDAJW-UHFFFAOYSA-N 4-(chloromethyl)-2-phenyl-1,3-oxazole Chemical compound ClCC1=COC(C=2C=CC=CC=2)=N1 ANSKJZIDWXDAJW-UHFFFAOYSA-N 0.000 description 1
• SNSKFUMCSUXJST-UHFFFAOYSA-N 4-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1COC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 SNSKFUMCSUXJST-UHFFFAOYSA-N 0.000 description 1
• UIVXXFYJRYVRKJ-UHFFFAOYSA-N 4-fluorobenzohydrazide Chemical compound NNC(=O)C1=CC=C(F)C=C1 UIVXXFYJRYVRKJ-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
• ZSGZJJKFLHWSHF-UHFFFAOYSA-N 5-(2-chloroethyl)-3-[3-fluoro-5-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC(F)=CC(C=2N=C(CCCl)ON=2)=C1 ZSGZJJKFLHWSHF-UHFFFAOYSA-N 0.000 description 1
• LMZZSCWNPOUYES-UHFFFAOYSA-N 5-(chloromethyl)-3-(4-fluorophenyl)-1,2,4-oxadiazole Chemical compound C1=CC(F)=CC=C1C1=NOC(CCl)=N1 LMZZSCWNPOUYES-UHFFFAOYSA-N 0.000 description 1
• JQVJAQPUFIIRJP-UHFFFAOYSA-N 5-(chloromethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole Chemical compound S1C(CCl)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 JQVJAQPUFIIRJP-UHFFFAOYSA-N 0.000 description 1
• FJMPRNQJJJGMJW-UHFFFAOYSA-N 7-(1,3-benzothiazol-2-ylmethoxy)-3-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(OCC=3SC4=CC=CC=C4N=3)=CC=C2C1=O FJMPRNQJJJGMJW-UHFFFAOYSA-N 0.000 description 1
• ZXAYMSZHBBVHFG-UHFFFAOYSA-N 7-(2-hydroxy-3-phenylpropoxy)-3-(4-methoxyphenyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(OCC(O)CC=3C=CC=CC=3)=CC=C2C1=O ZXAYMSZHBBVHFG-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 235000006491 Acacia senegal Nutrition 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 206010001605 Alcohol poisoning Diseases 0.000 description 1
• LYJHVEDILOKZCG-UHFFFAOYSA-N Allyl benzoate Chemical compound C=CCOC(=O)C1=CC=CC=C1 LYJHVEDILOKZCG-UHFFFAOYSA-N 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• 206010008479 Chest Pain Diseases 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease 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
• 229940126062 Compound A Drugs 0.000 description 1
• 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 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-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
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 101710088194 Dehydrogenase Proteins 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
• 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
• 206010052804 Drug tolerance Diseases 0.000 description 1
• 206010014561 Emphysema Diseases 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 229920003148 Eudragit® E polymer Polymers 0.000 description 1
• 206010016845 Foetal alcohol syndrome Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 206010019070 Hallucination, auditory Diseases 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000003698 Heroin Dependence Diseases 0.000 description 1
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• 206010022998 Irritability 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
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 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
• 241000699673 Mesocricetus auratus Species 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 102000009645 Mitochondrial Aldehyde Dehydrogenase Human genes 0.000 description 1
• 108010009513 Mitochondrial Aldehyde Dehydrogenase Proteins 0.000 description 1
• SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
• 208000006550 Mydriasis Diseases 0.000 description 1
• 235000009421 Myristica fragrans Nutrition 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 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
• BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 208000016222 Pancreatic disease Diseases 0.000 description 1
• 206010033864 Paranoia Diseases 0.000 description 1
• 208000027099 Paranoid disease Diseases 0.000 description 1
• 206010034158 Pathological gambling Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 206010036105 Polyneuropathy Diseases 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000001431 Psychomotor Agitation Diseases 0.000 description 1
• 208000028017 Psychotic disease Diseases 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
• 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 206010039203 Road traffic accident Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 206010042434 Sudden death Diseases 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
• 229920001615 Tragacanth Polymers 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• ALHZEIINTQJLOT-VKHMYHEASA-N [(2s)-1-chloro-1-oxopropan-2-yl] acetate Chemical compound ClC(=O)[C@H](C)OC(C)=O ALHZEIINTQJLOT-VKHMYHEASA-N 0.000 description 1
• MQMRMAMNWAHZBU-UHFFFAOYSA-N [4-[7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-4-oxochromen-3-yl]phenoxy]methyl dihydrogen phosphate Chemical compound C1=CC(OCOP(O)(=O)O)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O MQMRMAMNWAHZBU-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 150000000475 acetylene derivatives Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 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
• 229940025084 amphetamine Drugs 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000003444 anaesthetic effect Effects 0.000 description 1
• 238000000540 analysis of variance Methods 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
• 230000036506 anxiety Effects 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 239000007900 aqueous suspension 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
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 150000003936 benzamides Chemical class 0.000 description 1
• JFDZBHWFFUWGJE-KWCOIAHCSA-N benzonitrile Chemical group N#[11C]C1=CC=CC=C1 JFDZBHWFFUWGJE-KWCOIAHCSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 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
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 206010006451 bronchitis Diseases 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
• KCFKHWSNVPJBEP-UHFFFAOYSA-N butylazanium;sulfate Chemical compound CCCCN.CCCCN.OS(O)(=O)=O KCFKHWSNVPJBEP-UHFFFAOYSA-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
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 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
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 230000007681 cardiovascular toxicity Effects 0.000 description 1
• 231100000060 cardiovascular toxicity Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 230000001055 chewing effect Effects 0.000 description 1
• PJBIHXWYDMFGCV-UHFFFAOYSA-N chloro(chlorosulfonyloxy)methane Chemical compound ClCOS(Cl)(=O)=O PJBIHXWYDMFGCV-UHFFFAOYSA-N 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 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
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 201000001272 cocaine abuse Diseases 0.000 description 1
• 201000006145 cocaine dependence Diseases 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 231100000867 compulsive behavior Toxicity 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 230000001186 cumulative effect Effects 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
• 238000007405 data analysis Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 239000003479 dental cement Substances 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 125000005265 dialkylamine group Chemical group 0.000 description 1
• 125000005266 diarylamine group Chemical group 0.000 description 1
• VJBJIONRNUOWJD-UHFFFAOYSA-N diethyl 2-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CC1=COC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 VJBJIONRNUOWJD-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• YEBWYRCFFKIQNP-UHFFFAOYSA-N ditert-butyl [4-[7-[[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]methoxy]-4-oxochromen-3-yl]phenyl] phosphate Chemical compound C1=CC(OP(=O)(OC(C)(C)C)OC(C)(C)C)=CC=C1C1=COC2=CC(OCC=3N=C(OC=3)C=3C=C(C=C(F)C=3)C(F)(F)F)=CC=C2C1=O YEBWYRCFFKIQNP-UHFFFAOYSA-N 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 230000009483 enzymatic pathway Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 230000004149 ethanol metabolism Effects 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 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
• GLFJQXMGTAJTGY-AVBZIYQWSA-N ethyl (2s,5s)-5-[[(2s)-2-amino-3-(4-fluorophenyl)propanoyl]amino]-6-[3-[bis(2-chloroethyl)amino]phenyl]-2-(2-methylsulfanylethyl)-4-oxohexanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)C[C@@H](CCSC)C(=O)OCC)NC(=O)[C@@H](N)CC=1C=CC(F)=CC=1)C1=CC=CC(N(CCCl)CCCl)=C1 GLFJQXMGTAJTGY-AVBZIYQWSA-N 0.000 description 1
• IWCXWBNYKZAHKS-UHFFFAOYSA-N ethyl 3-[2-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]propanoate Chemical compound CCOC(=O)CCC1=COC(C=2C=C(C=C(F)C=2)C(F)(F)F)=N1 IWCXWBNYKZAHKS-UHFFFAOYSA-N 0.000 description 1
• MKGNEKMFBYWYEH-UHFFFAOYSA-N ethyl 5-pyridin-2-yl-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1=CC=CC=N1 MKGNEKMFBYWYEH-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 208000026934 fetal alcohol spectrum disease Diseases 0.000 description 1
• 201000007794 fetal alcohol syndrome Diseases 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019138 food restriction Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• HKQYGTCOTHHOMP-UHFFFAOYSA-N formononetin Chemical compound C1=CC(OC)=CC=C1C1=COC2=CC(O)=CC=C2C1=O HKQYGTCOTHHOMP-UHFFFAOYSA-N 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
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 229940014259 gelatin Drugs 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 230000026781 habituation Effects 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 125000005241 heteroarylamino group Chemical group 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
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 238000005286 illumination Methods 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• GPSDUZXPYCFOSQ-UHFFFAOYSA-M m-toluate Chemical compound CC1=CC=CC(C([O-])=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-M 0.000 description 1
• 239000001115 mace Substances 0.000 description 1
• OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical class [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
• 159000000003 magnesium salts Chemical class 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
• 239000011159 matrix material Substances 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
• 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
• VMWJNBBCTICBQB-UHFFFAOYSA-N methyl 3-[[3-[4-(methylcarbamoylamino)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)OC)=CC=C2C1=O VMWJNBBCTICBQB-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 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
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000002438 mitochondrial effect Effects 0.000 description 1
• 210000001700 mitochondrial membrane Anatomy 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 210000003205 muscle Anatomy 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
• KUKSUQKELVOKBH-UHFFFAOYSA-N n-[bis[(2-methylpropan-2-yl)oxy]phosphanyl]-n-ethylethanamine Chemical compound CCN(CC)P(OC(C)(C)C)OC(C)(C)C KUKSUQKELVOKBH-UHFFFAOYSA-N 0.000 description 1
• HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
• JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
• 208000015380 nutritional deficiency disease Diseases 0.000 description 1
• 235000003715 nutritional status Nutrition 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 235000020830 overeating Nutrition 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 150000002924 oxiranes Chemical class 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 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
• ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 230000007824 polyneuropathy Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• ZSWXMOQFFWMZQH-UHFFFAOYSA-M potassium;ditert-butyl phosphate Chemical compound [K+].CC(C)(C)OP([O-])(=O)OC(C)(C)C ZSWXMOQFFWMZQH-UHFFFAOYSA-M 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 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
• JHCGGPAVJCDDST-UHFFFAOYSA-N prop-2-enyl 3-[[3-(4-aminophenyl)-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(N)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)OCC=C)=CC=C2C1=O JHCGGPAVJCDDST-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• 150000003212 purines Chemical class 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
• 229940107700 pyruvic acid Drugs 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 group 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 201000004193 respiratory failure Diseases 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class 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
• 201000000980 schizophrenia Diseases 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 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
• 229920000260 silastic Polymers 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 239000012064 sodium phosphate buffer Substances 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 238000000935 solvent evaporation Methods 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 231100000736 substance abuse Toxicity 0.000 description 1
• 230000000153 supplemental effect Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
• 238000012385 systemic delivery Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 238000012353 t test Methods 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 235000019505 tobacco product Nutrition 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 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
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• XZZNDPSIHUTMOC-UHFFFAOYSA-N triphenyl phosphate Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)(=O)OC1=CC=CC=C1 XZZNDPSIHUTMOC-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
• 238000001291 vacuum drying Methods 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1