CA2427779A1 - Imidazo-triazine derivatives as ligands for gaba receptors - Google Patents

Info

Publication number

CA2427779A1

CA2427779A1 CA002427779A CA2427779A CA2427779A1 CA 2427779 A1 CA2427779 A1 CA 2427779A1 CA 002427779 A CA002427779 A CA 002427779A CA 2427779 A CA2427779 A CA 2427779A CA 2427779 A1 CA2427779 A1 CA 2427779A1

Authority

CA

Canada

Prior art keywords

fluoro

trifluoromethylimidazo

phenyl

triazine

triazin

Prior art date

2000-11-10

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

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000003446 ligand Substances 0.000 title abstract description 8
• XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 title description 3
• 102000005915 GABA Receptors Human genes 0.000 title 1
• 108010005551 GABA Receptors Proteins 0.000 title 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 16
• 230000002265 prevention Effects 0.000 claims abstract description 9
• 208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
• 230000036506 anxiety Effects 0.000 claims abstract description 5
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 3
• 230000002411 adverse Effects 0.000 claims abstract 3
• 150000001875 compounds Chemical class 0.000 claims description 250
• -1 2-hydroxyprop-2-yl Chemical group 0.000 claims description 167
• 238000000034 method Methods 0.000 claims description 108
• 239000001257 hydrogen Substances 0.000 claims description 60
• 229910052739 hydrogen Inorganic materials 0.000 claims description 60
• 150000003839 salts Chemical class 0.000 claims description 42
• 125000001153 fluoro group Chemical group F* 0.000 claims description 26
• 239000000651 prodrug Substances 0.000 claims description 26
• 229940002612 prodrug Drugs 0.000 claims description 26
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
• 239000003054 catalyst Substances 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 229910052736 halogen Chemical group 0.000 claims description 17
• 150000002367 halogens Chemical group 0.000 claims description 17
• WLPATYNQCGVFFH-UHFFFAOYSA-N 2-phenylbenzonitrile Chemical compound N#CC1=CC=CC=C1C1=CC=CC=C1 WLPATYNQCGVFFH-UHFFFAOYSA-N 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 14
• 229910052723 transition metal Inorganic materials 0.000 claims description 14
• 150000003624 transition metals Chemical class 0.000 claims description 14
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 150000002430 hydrocarbons Chemical group 0.000 claims description 8
• 239000004215 Carbon black (E152) Chemical group 0.000 claims description 7
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
• 229930195733 hydrocarbon Chemical group 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 claims description 3
• QDTNHUUKXGWKMO-UHFFFAOYSA-N 4-fluoro-2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound FC1=CC=C(C#N)C(C=2C(=CC=C(C=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)F)=C1 QDTNHUUKXGWKMO-UHFFFAOYSA-N 0.000 claims description 3
• 125000005620 boronic acid group Chemical group 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 238000010561 standard procedure Methods 0.000 claims description 3
• JAVOTZBYCURNSM-UHFFFAOYSA-N 1-[3-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C=2C(=CC=C(C=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)F)=C1 JAVOTZBYCURNSM-UHFFFAOYSA-N 0.000 claims description 2
• SJLQLNPRIHCHDY-UHFFFAOYSA-N 1-[3-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 SJLQLNPRIHCHDY-UHFFFAOYSA-N 0.000 claims description 2
• FMXZGRYCDIPZFC-UHFFFAOYSA-N 1-[4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 FMXZGRYCDIPZFC-UHFFFAOYSA-N 0.000 claims description 2
• PYMNCEZJPMDEPA-UHFFFAOYSA-N 2-[2-fluoro-3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound FC1=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=CC=C1C1=CC=CC=C1C#N PYMNCEZJPMDEPA-UHFFFAOYSA-N 0.000 claims description 2
• YQXPOJCRAKGRMA-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,3-oxazole Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=NC=CO1 YQXPOJCRAKGRMA-UHFFFAOYSA-N 0.000 claims description 2
• FNQVSSGSIGHASS-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,3-thiazole Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=NC=CS1 FNQVSSGSIGHASS-UHFFFAOYSA-N 0.000 claims description 2
• XAKLFBPRRVVCLE-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-5-nitro-1,3-thiazole Chemical compound S1C([N+](=O)[O-])=CN=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F XAKLFBPRRVVCLE-UHFFFAOYSA-N 0.000 claims description 2
• IYZAJLUGZRMKRF-UHFFFAOYSA-N 2-[3-(2-methylimidazo[1,2-b][1,2,4]triazin-7-yl)phenyl]benzonitrile Chemical compound N12N=C(C)C=NC2=NC=C1C(C=1)=CC=CC=1C1=CC=CC=C1C#N IYZAJLUGZRMKRF-UHFFFAOYSA-N 0.000 claims description 2
• BNQJKHFCSDKTCD-UHFFFAOYSA-N 2-[3-(3-methylimidazo[1,2-b][1,2,4]triazin-7-yl)phenyl]benzonitrile Chemical compound C=1N=C2N=C(C)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CC=C1C#N BNQJKHFCSDKTCD-UHFFFAOYSA-N 0.000 claims description 2
• LQJOSYXKEYEUAG-UHFFFAOYSA-N 2-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzaldehyde Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CC=C1C=O LQJOSYXKEYEUAG-UHFFFAOYSA-N 0.000 claims description 2
• CVPFASNYTKLDJC-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyridazin-3-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CN=N1 CVPFASNYTKLDJC-UHFFFAOYSA-N 0.000 claims description 2
• JFYJHRVIQOEMFA-UHFFFAOYSA-N 2-[7-[3-(3,5-difluoropyridin-2-yl)phenyl]imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=CC=1C1=NC=C(F)C=C1F JFYJHRVIQOEMFA-UHFFFAOYSA-N 0.000 claims description 2
• WIACWFSVQJVNGF-UHFFFAOYSA-N 2-[7-[4-fluoro-3-(3-fluoropyridin-2-yl)phenyl]imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=CC=C1F WIACWFSVQJVNGF-UHFFFAOYSA-N 0.000 claims description 2
• QSEBFHRZNPGODU-UHFFFAOYSA-N 2-[7-[4-fluoro-3-(5-fluoropyridin-2-yl)phenyl]imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=C(F)C=N1 QSEBFHRZNPGODU-UHFFFAOYSA-N 0.000 claims description 2
• HUPIGXXHGJDXHG-UHFFFAOYSA-N 3-(1,1-difluoroethyl)-7-(4-fluoro-3-pyridin-3-ylphenyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CN=C1 HUPIGXXHGJDXHG-UHFFFAOYSA-N 0.000 claims description 2
• YYIDJVSSJATAQW-UHFFFAOYSA-N 3-(2-fluoropropan-2-yl)-7-(4-fluoro-3-pyridin-3-ylphenyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(C)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CN=C1 YYIDJVSSJATAQW-UHFFFAOYSA-N 0.000 claims description 2
• PNRQFASVYBOWJQ-UHFFFAOYSA-N 3-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]aniline Chemical compound NC1=CC=CC(C=2C(=CC=C(C=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)F)=C1 PNRQFASVYBOWJQ-UHFFFAOYSA-N 0.000 claims description 2
• BWFZJAHQMPIHMS-UHFFFAOYSA-N 3-[3-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]prop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=CC(C=2C(=CC=C(C=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)F)=C1 BWFZJAHQMPIHMS-UHFFFAOYSA-N 0.000 claims description 2
• YIPZYLYYEIVKEQ-UHFFFAOYSA-N 3-tert-butyl-7-(4-fluoro-3-pyridin-2-ylphenyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(C)(C)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CC=N1 YIPZYLYYEIVKEQ-UHFFFAOYSA-N 0.000 claims description 2
• VSZZYAJBIGSJJF-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyrimidine-5-carbonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=NC=C1C#N VSZZYAJBIGSJJF-UHFFFAOYSA-N 0.000 claims description 2
• CSCIMRWVMYPARG-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,3-thiazole Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CSC=N1 CSCIMRWVMYPARG-UHFFFAOYSA-N 0.000 claims description 2
• BWKUJRRTHFXVQJ-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzaldehyde Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=C(C=O)C=C1 BWKUJRRTHFXVQJ-UHFFFAOYSA-N 0.000 claims description 2
• UKMPTAZPLVNBGN-UHFFFAOYSA-N 4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,3-thiazole Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CSC=N1 UKMPTAZPLVNBGN-UHFFFAOYSA-N 0.000 claims description 2
• BJHWIIMZXLYGMX-UHFFFAOYSA-N 4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzaldehyde Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=C(C=O)C=C1 BJHWIIMZXLYGMX-UHFFFAOYSA-N 0.000 claims description 2
• CKGQTLXSYOGMAD-UHFFFAOYSA-N 4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=C(C#N)C=C1 CKGQTLXSYOGMAD-UHFFFAOYSA-N 0.000 claims description 2
• LGGFECKRTVHJEC-UHFFFAOYSA-N 5-fluoro-2-[2-fluoro-5-[3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=C(F)C=C1C#N LGGFECKRTVHJEC-UHFFFAOYSA-N 0.000 claims description 2
• FNSOTIBCHRCQOM-UHFFFAOYSA-N 5-methyl-2-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-3h-1,2,4-oxadiazole Chemical compound O1C(C)=NCN1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 FNSOTIBCHRCQOM-UHFFFAOYSA-N 0.000 claims description 2
• NYNXZPNTZUUTII-UHFFFAOYSA-N 7-(3-pyridin-2-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CC=N1 NYNXZPNTZUUTII-UHFFFAOYSA-N 0.000 claims description 2
• MXHKCAVBILRRFE-UHFFFAOYSA-N 7-(3-pyridin-4-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=NC=C1 MXHKCAVBILRRFE-UHFFFAOYSA-N 0.000 claims description 2
• KEGCQENQLINORT-UHFFFAOYSA-N 7-(3-pyrrol-1-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1N1C=CC=C1 KEGCQENQLINORT-UHFFFAOYSA-N 0.000 claims description 2
• CAMGAXYEZCKUEL-UHFFFAOYSA-N 7-(3-thiophen-2-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CS1 CAMGAXYEZCKUEL-UHFFFAOYSA-N 0.000 claims description 2
• KPPJEGSZVMTVRB-UHFFFAOYSA-N 7-(3-thiophen-3-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C=1C=CSC=1 KPPJEGSZVMTVRB-UHFFFAOYSA-N 0.000 claims description 2
• LSXPZNREAAPJKF-UHFFFAOYSA-N 7-(4-fluoro-3-imidazol-1-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1N1C=CN=C1 LSXPZNREAAPJKF-UHFFFAOYSA-N 0.000 claims description 2
• YNUCMMQAYPZJBU-UHFFFAOYSA-N 7-(4-fluoro-3-pyrazol-1-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1N1C=CC=N1 YNUCMMQAYPZJBU-UHFFFAOYSA-N 0.000 claims description 2
• WDOHOIKMRMPGRB-UHFFFAOYSA-N 7-(4-fluoro-3-pyridin-3-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=CN=C1 WDOHOIKMRMPGRB-UHFFFAOYSA-N 0.000 claims description 2
• XRHDPYOWXFHGGC-UHFFFAOYSA-N 7-(4-fluoro-3-pyridin-4-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=NC=C1 XRHDPYOWXFHGGC-UHFFFAOYSA-N 0.000 claims description 2
• ZZCDKXJZGLAQMN-UHFFFAOYSA-N 7-[3-(1,2,4-triazol-1-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1N1C=NC=N1 ZZCDKXJZGLAQMN-UHFFFAOYSA-N 0.000 claims description 2
• UUZPXUGZZUUMCF-UHFFFAOYSA-N 7-[3-(1-methyl-1,2,4-triazol-3-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CN1C=NC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 UUZPXUGZZUUMCF-UHFFFAOYSA-N 0.000 claims description 2
• YZKQQDDYAPFXKL-UHFFFAOYSA-N 7-[3-(1-methylpyrazol-3-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CN1C=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 YZKQQDDYAPFXKL-UHFFFAOYSA-N 0.000 claims description 2
• DMBVOOINJRHNLD-UHFFFAOYSA-N 7-[3-(2-methoxyphenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound COC1=CC=CC=C1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 DMBVOOINJRHNLD-UHFFFAOYSA-N 0.000 claims description 2
• KCSSZQYRTOUTCH-UHFFFAOYSA-N 7-[3-(2-methyltetrazol-5-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CN1N=NC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 KCSSZQYRTOUTCH-UHFFFAOYSA-N 0.000 claims description 2
• DZJITHDTCFWHSD-UHFFFAOYSA-N 7-[3-(2-methyltriazol-4-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CN1N=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 DZJITHDTCFWHSD-UHFFFAOYSA-N 0.000 claims description 2
• LQWDTLCEHXOMAL-UHFFFAOYSA-N 7-[3-(3,4-dimethoxyphenyl)-4-fluorophenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F LQWDTLCEHXOMAL-UHFFFAOYSA-N 0.000 claims description 2
• IVSKTKMJNWWHAR-UHFFFAOYSA-N 7-[3-(3,5-difluoropyridin-2-yl)-4-fluorophenyl]-3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(C)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=C(F)C=C1F IVSKTKMJNWWHAR-UHFFFAOYSA-N 0.000 claims description 2
• UJNMXTRHIFJXRY-UHFFFAOYSA-N 7-[3-(3,5-difluoropyridin-2-yl)-4-fluorophenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC(F)=CN=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F UJNMXTRHIFJXRY-UHFFFAOYSA-N 0.000 claims description 2
• JRLZVTMBPVCSGQ-UHFFFAOYSA-N 7-[3-(3-nitrophenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 JRLZVTMBPVCSGQ-UHFFFAOYSA-N 0.000 claims description 2
• WYSSXCWGFXLFKU-UHFFFAOYSA-N 7-[3-(4-methylpyridin-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CC1=CC=NC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 WYSSXCWGFXLFKU-UHFFFAOYSA-N 0.000 claims description 2
• BRXQXPYJZTUBPG-UHFFFAOYSA-N 7-[3-(5-fluoropyridin-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=CC(F)=CC=C1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 BRXQXPYJZTUBPG-UHFFFAOYSA-N 0.000 claims description 2
• JKDMQLNJUOITRZ-UHFFFAOYSA-N 7-[3-(6-methoxypyridazin-4-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=NC(OC)=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 JKDMQLNJUOITRZ-UHFFFAOYSA-N 0.000 claims description 2
• SKAHGWCPSRXZOH-UHFFFAOYSA-N 7-[3-(furan-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CO1 SKAHGWCPSRXZOH-UHFFFAOYSA-N 0.000 claims description 2
• RRGSMHWXXGVRPQ-UHFFFAOYSA-N 7-[3-(furan-3-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C=1C=COC=1 RRGSMHWXXGVRPQ-UHFFFAOYSA-N 0.000 claims description 2
• KWZIJLQUJGIGJH-UHFFFAOYSA-N 7-[4-fluoro-3-(1,2,4-triazol-1-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1N1C=NC=N1 KWZIJLQUJGIGJH-UHFFFAOYSA-N 0.000 claims description 2
• DIHGZZHFINLASN-UHFFFAOYSA-N 7-[4-fluoro-3-(1-methylpyrazol-4-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=NN(C)C=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F DIHGZZHFINLASN-UHFFFAOYSA-N 0.000 claims description 2
• PXQHDLWGOAISIM-UHFFFAOYSA-N 7-[4-fluoro-3-(2-methoxyphenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound COC1=CC=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F PXQHDLWGOAISIM-UHFFFAOYSA-N 0.000 claims description 2
• RMBZRSWXPSLETL-UHFFFAOYSA-N 7-[4-fluoro-3-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F RMBZRSWXPSLETL-UHFFFAOYSA-N 0.000 claims description 2
• ZQVZEAQJXXDHIY-UHFFFAOYSA-N 7-[4-fluoro-3-(2-methyltetrazol-5-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CN1N=NC(C=2C(=CC=C(C=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)F)=N1 ZQVZEAQJXXDHIY-UHFFFAOYSA-N 0.000 claims description 2
• LVIZGUWETGQRJR-UHFFFAOYSA-N 7-[4-fluoro-3-(4-fluoropyridin-3-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=NC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F LVIZGUWETGQRJR-UHFFFAOYSA-N 0.000 claims description 2
• VUPNXVABOXDOJC-UHFFFAOYSA-N 7-[4-fluoro-3-(4-methoxyphenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=CC(OC)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F VUPNXVABOXDOJC-UHFFFAOYSA-N 0.000 claims description 2
• AFHKBGYETHVEEX-UHFFFAOYSA-N 7-[4-fluoro-3-(4-methylsulfanylphenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=CC(SC)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F AFHKBGYETHVEEX-UHFFFAOYSA-N 0.000 claims description 2
• GZMDZIBAQQBRAC-UHFFFAOYSA-N 7-[4-fluoro-3-(5-fluoropyridin-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=CC(F)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F GZMDZIBAQQBRAC-UHFFFAOYSA-N 0.000 claims description 2
• FKDJTACGRRGINF-UHFFFAOYSA-N 7-[4-fluoro-3-(furan-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=CO1 FKDJTACGRRGINF-UHFFFAOYSA-N 0.000 claims description 2
• 150000002009 diols Chemical class 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
• PCZLQMGFNUNVOM-UHFFFAOYSA-N 3-fluoro-2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=C(F)C=CC=C1C#N PCZLQMGFNUNVOM-UHFFFAOYSA-N 0.000 claims 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 230000000926 neurological effect Effects 0.000 claims 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
• RXSVZLWLJFRDMA-UHFFFAOYSA-N 1-[5-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]thiophen-2-yl]ethanone Chemical compound S1C(C(=O)C)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F RXSVZLWLJFRDMA-UHFFFAOYSA-N 0.000 claims 1
• JEGFGPZYKCBKBU-UHFFFAOYSA-N 2-(2-fluoro-5-imidazo[1,2-b][1,2,4]triazin-7-ylphenyl)benzonitrile Chemical compound FC1=CC=C(C=2N3N=CC=NC3=NC=2)C=C1C1=CC=CC=C1C#N JEGFGPZYKCBKBU-UHFFFAOYSA-N 0.000 claims 1
• VDUAIIDPYNJYMB-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CC=C1C#N VDUAIIDPYNJYMB-UHFFFAOYSA-N 0.000 claims 1
• VBXZLYYHFDVNEN-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyridine-3-carbonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=CC=C1C#N VBXZLYYHFDVNEN-UHFFFAOYSA-N 0.000 claims 1
• HBLJPARREFIRGR-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-n,n-dimethyl-1,3-thiazole-5-carboxamide Chemical compound S1C(C(=O)N(C)C)=CN=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F HBLJPARREFIRGR-UHFFFAOYSA-N 0.000 claims 1
• HCKOUSVQWKTONU-UHFFFAOYSA-N 2-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=CC=C1C#N HCKOUSVQWKTONU-UHFFFAOYSA-N 0.000 claims 1
• LKODPGNJHMBDDK-UHFFFAOYSA-N 2-[3-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CC=C1C#N LKODPGNJHMBDDK-UHFFFAOYSA-N 0.000 claims 1
• QBVJKQBZLPVJDV-UHFFFAOYSA-N 2-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,3-thiazole Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=NC=CS1 QBVJKQBZLPVJDV-UHFFFAOYSA-N 0.000 claims 1
• WCXZBXSJLJZSSH-UHFFFAOYSA-N 2-[7-(2-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1F)=CC=CC=1C1=CC=NC=C1 WCXZBXSJLJZSSH-UHFFFAOYSA-N 0.000 claims 1
• DZQUECBNJGMGAE-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyridin-2-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CC=N1 DZQUECBNJGMGAE-UHFFFAOYSA-N 0.000 claims 1
• LLHQBHOWDZNCNK-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyridin-3-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CN=C1 LLHQBHOWDZNCNK-UHFFFAOYSA-N 0.000 claims 1
• BPTASZCHRIMWEF-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyridin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=NC=C1 BPTASZCHRIMWEF-UHFFFAOYSA-N 0.000 claims 1
• YSCQXQSSTHEHJZ-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyrimidin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=NC=N1 YSCQXQSSTHEHJZ-UHFFFAOYSA-N 0.000 claims 1
• PFJHXYJLEIZLGQ-UHFFFAOYSA-N 2-[7-[3-(3,5-difluoropyridin-2-yl)-4-fluorophenyl]imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=C(F)C=C1F PFJHXYJLEIZLGQ-UHFFFAOYSA-N 0.000 claims 1
• ZYODOZATSVMRJQ-UHFFFAOYSA-N 3,5-difluoro-2-[2-fluoro-5-[3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=C(F)C=C(F)C=C1C#N ZYODOZATSVMRJQ-UHFFFAOYSA-N 0.000 claims 1
• LFWROMCSALLJEF-UHFFFAOYSA-N 3-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]thiophene-2-carbaldehyde Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C=1C=CSC=1C=O LFWROMCSALLJEF-UHFFFAOYSA-N 0.000 claims 1
• SMXUZEFGNVLKGG-UHFFFAOYSA-N 3-fluoro-2-[2-fluoro-5-[3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(F)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=C(F)C=CC=C1C#N SMXUZEFGNVLKGG-UHFFFAOYSA-N 0.000 claims 1
• FMUXIJDACFSDHS-UHFFFAOYSA-N 3-tert-butyl-7-(4-fluoro-3-pyridin-3-ylphenyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(C)(C)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=CN=C1 FMUXIJDACFSDHS-UHFFFAOYSA-N 0.000 claims 1
• YLDRVNNGBACDSD-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyridine-3-carbonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=NC=C1C#N YLDRVNNGBACDSD-UHFFFAOYSA-N 0.000 claims 1
• SQZQKZGAXIGWFH-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-3,5-dimethyl-1,2-oxazole Chemical compound CC1=NOC(C)=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F SQZQKZGAXIGWFH-UHFFFAOYSA-N 0.000 claims 1
• CGLOVIUBADXELF-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenol Chemical compound C1=CC(O)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F CGLOVIUBADXELF-UHFFFAOYSA-N 0.000 claims 1
• VDKKQZSNIBJNSR-UHFFFAOYSA-N 5-fluoro-2-[3-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=CC=1C1=CC=C(F)C=C1C#N VDKKQZSNIBJNSR-UHFFFAOYSA-N 0.000 claims 1
• HHSYSDDEPRWLSN-UHFFFAOYSA-N 7-(3-pyridin-3-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CC=CN=C1 HHSYSDDEPRWLSN-UHFFFAOYSA-N 0.000 claims 1
• ONEYJCPOQUKAIR-UHFFFAOYSA-N 7-(4-chloro-3-pyridin-3-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=C(Cl)C=1C1=CC=CN=C1 ONEYJCPOQUKAIR-UHFFFAOYSA-N 0.000 claims 1
• LPJNVDXBKUPNFK-UHFFFAOYSA-N 7-(4-fluoro-3-pyridin-2-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=C1C1=CC=CC=N1 LPJNVDXBKUPNFK-UHFFFAOYSA-N 0.000 claims 1
• VODSAYQEQFPKJA-UHFFFAOYSA-N 7-[3-(4-fluoropyridin-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=CC=NC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 VODSAYQEQFPKJA-UHFFFAOYSA-N 0.000 claims 1
• 229910005960 SO2 a Inorganic materials 0.000 claims 1
• KHUKUFKSRRGWCP-UHFFFAOYSA-N [4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 KHUKUFKSRRGWCP-UHFFFAOYSA-N 0.000 claims 1
• MQGVSNJQXHZFOG-UHFFFAOYSA-N n-[3-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 MQGVSNJQXHZFOG-UHFFFAOYSA-N 0.000 claims 1
• 108091008681 GABAA receptors Proteins 0.000 abstract description 36
• 102000027484 GABAA receptors Human genes 0.000 abstract description 34
• 206010010904 Convulsion Diseases 0.000 abstract description 4
• 230000008901 benefit Effects 0.000 abstract description 4
• 208000010877 cognitive disease Diseases 0.000 abstract description 3
• 230000036461 convulsion Effects 0.000 abstract description 3
• 210000003169 central nervous system Anatomy 0.000 abstract description 2
• SKQCVELLWZOJOG-UHFFFAOYSA-N 7-phenylimidazo[1,2-b][1,2,4]triazine Chemical class C=1N=C2N=CC=NN2C=1C1=CC=CC=C1 SKQCVELLWZOJOG-UHFFFAOYSA-N 0.000 abstract 1
• 239000000203 mixture Substances 0.000 description 239
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 208
• 239000007787 solid Substances 0.000 description 167
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 158
• 238000005160 1H NMR spectroscopy Methods 0.000 description 156
• 239000000243 solution Substances 0.000 description 151
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 140
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 126
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 112
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 112
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 111
• 239000000741 silica gel Substances 0.000 description 104
• 229910002027 silica gel Inorganic materials 0.000 description 104
• 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 84
• 238000006243 chemical reaction Methods 0.000 description 71
• 229910052757 nitrogen Inorganic materials 0.000 description 70
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
• 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 64
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 57
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 52
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 50
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 44
• 238000000746 purification Methods 0.000 description 44
• 238000004587 chromatography analysis Methods 0.000 description 43
• 239000002904 solvent Substances 0.000 description 43
• 238000003818 flash chromatography Methods 0.000 description 42
• 230000002829 reductive effect Effects 0.000 description 42
• 125000000217 alkyl group Chemical group 0.000 description 41
• 239000003921 oil Substances 0.000 description 40
• 235000019198 oils Nutrition 0.000 description 40
• 238000005481 NMR spectroscopy Methods 0.000 description 39
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
• 239000012267 brine Substances 0.000 description 34
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 239000000284 extract Substances 0.000 description 32
• 239000000706 filtrate Substances 0.000 description 32
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 28
• 238000003756 stirring Methods 0.000 description 28
• 238000001914 filtration Methods 0.000 description 26
• 235000011056 potassium acetate Nutrition 0.000 description 25
• 239000011541 reaction mixture Substances 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 23
• MDNDJMCSXOXBFZ-UHFFFAOYSA-N 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5,5-dimethyl-1,3,2-dioxaborinane Chemical compound O1CC(C)(C)COB1B1OCC(C)(C)CO1 MDNDJMCSXOXBFZ-UHFFFAOYSA-N 0.000 description 23
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
• 238000010992 reflux Methods 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• 239000000047 product Substances 0.000 description 21
• RXZLFBDCEQEETM-UHFFFAOYSA-N 7-bromo-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(F)(F)F)C=NN2C(Br)=CN=C21 RXZLFBDCEQEETM-UHFFFAOYSA-N 0.000 description 20
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 19
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 18
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 18
• BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 18
• 150000002431 hydrogen Chemical class 0.000 description 18
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 18
• 101150041968 CDC13 gene Proteins 0.000 description 17
• 230000027455 binding Effects 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• 239000000725 suspension Substances 0.000 description 17
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 238000001816 cooling Methods 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 239000012074 organic phase Substances 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 14
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 14
• 235000010288 sodium nitrite Nutrition 0.000 description 14
• 125000001424 substituent group Chemical group 0.000 description 14
• FXEVKZIXXGDLFW-UHFFFAOYSA-N 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC([N+]([O-])=O)=CC=C1F FXEVKZIXXGDLFW-UHFFFAOYSA-N 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 12
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 12
• NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 12
• 238000010438 heat treatment Methods 0.000 description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• 239000002253 acid Substances 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000000377 silicon dioxide Substances 0.000 description 11
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 235000011114 ammonium hydroxide Nutrition 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 10
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
• 125000004076 pyridyl group Chemical group 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• 239000012258 stirred mixture Substances 0.000 description 10
• YKXKGLXAERYSJN-UHFFFAOYSA-N 3-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(F)C(C=2C=NC=CC=2)=C1 YKXKGLXAERYSJN-UHFFFAOYSA-N 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 9
• 238000004440 column chromatography Methods 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 125000002541 furyl group Chemical group 0.000 description 9
• 239000011698 potassium fluoride Substances 0.000 description 9
• 235000003270 potassium fluoride Nutrition 0.000 description 9
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 8
• FAWMTDSAMOCUAR-UHFFFAOYSA-N 2-bromo-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Br)=C1 FAWMTDSAMOCUAR-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 235000011054 acetic acid Nutrition 0.000 description 8
• 229940049706 benzodiazepine Drugs 0.000 description 8
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
• 229910000160 potassium phosphate Inorganic materials 0.000 description 8
• 235000011009 potassium phosphates Nutrition 0.000 description 8
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
• 125000003545 alkoxy group Chemical group 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• 125000003963 dichloro group Chemical group Cl* 0.000 description 7
• 239000003365 glass fiber Substances 0.000 description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 125000000335 thiazolyl group Chemical group 0.000 description 7
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 6
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• 206010012289 Dementia Diseases 0.000 description 6
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 6
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
• 239000000556 agonist Substances 0.000 description 6
• 230000000949 anxiolytic effect Effects 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 239000012131 assay buffer Substances 0.000 description 6
• 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 6
• QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
• 125000004802 cyanophenyl group Chemical group 0.000 description 6
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 6
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 238000001953 recrystallisation Methods 0.000 description 6
• 235000017281 sodium acetate Nutrition 0.000 description 6
• BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 5
• LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 5
• RTBGBGREMLPTRD-UHFFFAOYSA-N 4-fluoro-3-pyridin-3-ylaniline Chemical compound NC1=CC=C(F)C(C=2C=NC=CC=2)=C1 RTBGBGREMLPTRD-UHFFFAOYSA-N 0.000 description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 5
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 5
• 230000000712 assembly Effects 0.000 description 5
• 238000000429 assembly Methods 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 230000005587 bubbling Effects 0.000 description 5
• 125000000753 cycloalkyl group Chemical group 0.000 description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 5
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 239000002002 slurry Substances 0.000 description 5
• 235000011150 stannous chloride Nutrition 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 125000001544 thienyl group Chemical group 0.000 description 5
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 5
• MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 description 4
• RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 4
• NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 4
• PELFSPIQQQEARZ-UHFFFAOYSA-N 2-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(F)C(C=2C(=CC=CC=2)C#N)=C1 PELFSPIQQQEARZ-UHFFFAOYSA-N 0.000 description 4
• HEPPAPZASXFWTB-UHFFFAOYSA-N 3,3-dibromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)C(Br)Br HEPPAPZASXFWTB-UHFFFAOYSA-N 0.000 description 4
• QGACODVONZZZNW-UHFFFAOYSA-N 3-(5-bromo-2-fluorophenyl)pyridine Chemical compound FC1=CC=C(Br)C=C1C1=CC=CN=C1 QGACODVONZZZNW-UHFFFAOYSA-N 0.000 description 4
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• 235000019502 Orange oil Nutrition 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
• 239000002249 anxiolytic agent Substances 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 125000001246 bromo group Chemical group Br* 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 125000006001 difluoroethyl group Chemical group 0.000 description 4
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 239000012065 filter cake Substances 0.000 description 4
• 229960004381 flumazenil Drugs 0.000 description 4
• 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 4
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 4
• SYLTXFOKMOCILU-UHFFFAOYSA-N imidazo[1,2-b][1,2,4]triazine Chemical class N1=CC=NC2=NC=CN21 SYLTXFOKMOCILU-UHFFFAOYSA-N 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• 238000011068 loading method Methods 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 125000006501 nitrophenyl group Chemical group 0.000 description 4
• 239000010502 orange oil Substances 0.000 description 4
• 125000002971 oxazolyl group Chemical group 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 125000003373 pyrazinyl group Chemical group 0.000 description 4
• 125000003226 pyrazolyl group Chemical group 0.000 description 4
• 125000002098 pyridazinyl group Chemical group 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 125000000168 pyrrolyl group Chemical group 0.000 description 4
• 239000001632 sodium acetate Substances 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 125000001113 thiadiazolyl group Chemical group 0.000 description 4
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 4
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 4
• 125000001425 triazolyl group Chemical group 0.000 description 4
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
• DWWBIBIBBJFVDH-UHFFFAOYSA-N (4-fluoro-3-pyridin-2-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2N=CC=CC=2)=C1 DWWBIBIBBJFVDH-UHFFFAOYSA-N 0.000 description 3
• OTXHZHQQWQTQMW-UHFFFAOYSA-N (diaminomethylideneamino)azanium;hydrogen carbonate Chemical compound OC([O-])=O.N[NH2+]C(N)=N OTXHZHQQWQTQMW-UHFFFAOYSA-N 0.000 description 3
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
• RPKSFTNSDNIOLV-UHFFFAOYSA-N 2-(2-fluoro-5-nitrophenyl)pyridine-3-carbonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC=CN=2)C#N)=C1 RPKSFTNSDNIOLV-UHFFFAOYSA-N 0.000 description 3
• HFCLWYJKVXCCGQ-UHFFFAOYSA-N 2-(5-amino-2-fluorophenyl)-5-fluorobenzonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CC(F)=CC=2)C#N)=C1 HFCLWYJKVXCCGQ-UHFFFAOYSA-N 0.000 description 3
• MMMLSQHYLHCHIY-UHFFFAOYSA-N 2-(5-amino-2-fluorophenyl)pyridine-3-carbonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CC=CN=2)C#N)=C1 MMMLSQHYLHCHIY-UHFFFAOYSA-N 0.000 description 3
• WLPBLIAXAWKMEB-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-5-fluorobenzonitrile Chemical compound N#CC1=CC(F)=CC=C1C1=CC(Br)=CC=C1F WLPBLIAXAWKMEB-UHFFFAOYSA-N 0.000 description 3
• HZWDVQBQUFRXTO-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)pyridine-3-carbonitrile Chemical compound FC1=CC=C(Br)C=C1C1=NC=CC=C1C#N HZWDVQBQUFRXTO-UHFFFAOYSA-N 0.000 description 3
• IIPUMDWNVSSYJT-UHFFFAOYSA-N 2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(C=2C(=CC=CC=2)C#N)=C1 IIPUMDWNVSSYJT-UHFFFAOYSA-N 0.000 description 3
• DKKKPQOSPBCTLK-UHFFFAOYSA-N 2-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]-5-fluorobenzonitrile Chemical compound O1CC(C)(C)COB1C1=CC=C(F)C(C=2C(=CC(F)=CC=2)C#N)=C1 DKKKPQOSPBCTLK-UHFFFAOYSA-N 0.000 description 3
• AFMPMSCZPVNPEM-UHFFFAOYSA-N 2-bromobenzonitrile Chemical compound BrC1=CC=CC=C1C#N AFMPMSCZPVNPEM-UHFFFAOYSA-N 0.000 description 3
• JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
• KBEDYRBETKKHHO-UHFFFAOYSA-N 3-(3-bromophenyl)-1-methyl-1,2,4-triazole Chemical compound CN1C=NC(C=2C=C(Br)C=CC=2)=N1 KBEDYRBETKKHHO-UHFFFAOYSA-N 0.000 description 3
• KOWPUNQBGWIERF-UHFFFAOYSA-N 3-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Br)=C1 KOWPUNQBGWIERF-UHFFFAOYSA-N 0.000 description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
• KXLBUYFCVSFJBX-UHFFFAOYSA-N 4-(3-bromophenyl)-2-methyltriazole Chemical compound CN1N=CC(C=2C=C(Br)C=CC=2)=N1 KXLBUYFCVSFJBX-UHFFFAOYSA-N 0.000 description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
• RMMXULAVPASGOF-UHFFFAOYSA-N 5-(trifluoromethyl)-1,2,4-triazin-3-amine Chemical compound NC1=NN=CC(C(F)(F)F)=N1 RMMXULAVPASGOF-UHFFFAOYSA-N 0.000 description 3
• LYHLDFUYIGCHTO-UHFFFAOYSA-N 7-(3-bromophenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C1=CC=CC(Br)=C1 LYHLDFUYIGCHTO-UHFFFAOYSA-N 0.000 description 3
• 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 3
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
• 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
• 102000020897 Formins Human genes 0.000 description 3
• 108091022623 Formins Proteins 0.000 description 3
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
• 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 3
• 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 3
• 239000007832 Na2SO4 Substances 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 206010039897 Sedation Diseases 0.000 description 3
• 206010047700 Vomiting Diseases 0.000 description 3
• JVHNKZBMDNRVRP-UHFFFAOYSA-N [3-(3,5-difluoropyridin-2-yl)-4-fluorophenyl]boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2C(=CC(F)=CN=2)F)=C1 JVHNKZBMDNRVRP-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 125000004414 alkyl thio group Chemical group 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 230000019771 cognition Effects 0.000 description 3
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 230000009871 nonspecific binding Effects 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000002953 preparative HPLC Methods 0.000 description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
• JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 239000002287 radioligand Substances 0.000 description 3
• 239000000018 receptor agonist Substances 0.000 description 3
• 229940044601 receptor agonist Drugs 0.000 description 3
• 230000036280 sedation Effects 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
• YOZIWBXJOJWXAW-UHFFFAOYSA-N (2-fluoro-3-pyridin-4-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=2C=CN=CC=2)=C1F YOZIWBXJOJWXAW-UHFFFAOYSA-N 0.000 description 2
• QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 2
• SGACJBBAKYLFRV-UHFFFAOYSA-N (4-fluoro-3-pyridazin-3-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2N=NC=CC=2)=C1 SGACJBBAKYLFRV-UHFFFAOYSA-N 0.000 description 2
• OLPRXNATYALDJT-UHFFFAOYSA-N (4-fluoro-3-pyridazin-4-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2C=NN=CC=2)=C1 OLPRXNATYALDJT-UHFFFAOYSA-N 0.000 description 2
• OWNTXISUQWLBMC-UHFFFAOYSA-N (4-fluoro-3-pyridin-4-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2C=CN=CC=2)=C1 OWNTXISUQWLBMC-UHFFFAOYSA-N 0.000 description 2
• LHNJJBIAEQMRCI-UHFFFAOYSA-N (4-fluoro-3-pyrimidin-4-ylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2N=CN=CC=2)=C1 LHNJJBIAEQMRCI-UHFFFAOYSA-N 0.000 description 2
• HTJMXYRLEDBSLT-UHFFFAOYSA-N 1,2,4,5-tetrazine Chemical compound C1=NN=CN=N1 HTJMXYRLEDBSLT-UHFFFAOYSA-N 0.000 description 2
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 2
• JTOQNQIBUCTGFM-UHFFFAOYSA-N 1-(2-fluoro-4-nitrophenyl)-1,2,4-triazole Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1N=CN=C1 JTOQNQIBUCTGFM-UHFFFAOYSA-N 0.000 description 2
• YNYHDGYGCYUVOE-UHFFFAOYSA-N 1-(2-fluoro-4-nitrophenyl)pyrazole Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1N=CC=C1 YNYHDGYGCYUVOE-UHFFFAOYSA-N 0.000 description 2
• YJQBLWWHFYAXRA-UHFFFAOYSA-N 1-(3-bromophenyl)-1,2,4-triazole Chemical compound BrC1=CC=CC(N2N=CN=C2)=C1 YJQBLWWHFYAXRA-UHFFFAOYSA-N 0.000 description 2
• MPLAQLUPIZUNTG-UHFFFAOYSA-N 1-(5-bromo-2-fluorophenyl)-1,2,4-triazole Chemical compound FC1=CC=C(Br)C=C1N1N=CN=C1 MPLAQLUPIZUNTG-UHFFFAOYSA-N 0.000 description 2
• REWIWNMCZSYGHF-UHFFFAOYSA-N 1-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]pyrazole Chemical compound O1CC(C)(C)COB1C1=CC=C(F)C(N2N=CC=C2)=C1 REWIWNMCZSYGHF-UHFFFAOYSA-N 0.000 description 2
• CTPUUDQIXKUAMO-UHFFFAOYSA-N 1-bromo-3-iodobenzene Chemical compound BrC1=CC=CC(I)=C1 CTPUUDQIXKUAMO-UHFFFAOYSA-N 0.000 description 2
• WPIUPNQGNRBDPK-UHFFFAOYSA-N 1-fluoro-2-(2-methylsulfanylphenyl)-4-nitrobenzene Chemical group CSC1=CC=CC=C1C1=CC([N+]([O-])=O)=CC=C1F WPIUPNQGNRBDPK-UHFFFAOYSA-N 0.000 description 2
• GKWOSYZICRXPCI-UHFFFAOYSA-N 2,4,6-tribromo-3,5-difluoropyridine Chemical compound FC1=C(Br)N=C(Br)C(F)=C1Br GKWOSYZICRXPCI-UHFFFAOYSA-N 0.000 description 2
• GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 2
• DSRKHXWSCLXCCF-UHFFFAOYSA-N 2,4-dibromo-3,5-difluoro-6-(2-fluoro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=C(Br)C(F)=C(Br)N=2)F)=C1 DSRKHXWSCLXCCF-UHFFFAOYSA-N 0.000 description 2
• IMZUBYQNCNXLRQ-UHFFFAOYSA-N 2,4-dibromo-3,5-difluoro-6-(3-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=CC(C=2C(=C(Br)C(F)=C(Br)N=2)F)=C1 IMZUBYQNCNXLRQ-UHFFFAOYSA-N 0.000 description 2
• AEDYWHYTTIQBCN-UHFFFAOYSA-N 2-(2-fluoro-5-nitrophenyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC=CC=2)C#N)=C1 AEDYWHYTTIQBCN-UHFFFAOYSA-N 0.000 description 2
• SMRCYJAYINPOKU-UHFFFAOYSA-N 2-(2-fluoro-5-nitrophenyl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CC([N+]([O-])=O)=CC=C1F SMRCYJAYINPOKU-UHFFFAOYSA-N 0.000 description 2
• NOKSMMMLCXGSSA-UHFFFAOYSA-N 2-(2-fluoro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2N=CC=CC=2)=C1 NOKSMMMLCXGSSA-UHFFFAOYSA-N 0.000 description 2
• GGJLSLOHVMYBDP-UHFFFAOYSA-N 2-(3-aminophenyl)benzonitrile Chemical compound NC1=CC=CC(C=2C(=CC=CC=2)C#N)=C1 GGJLSLOHVMYBDP-UHFFFAOYSA-N 0.000 description 2
• HYGFXMKWWQYTEU-UHFFFAOYSA-N 2-(3-bromophenyl)-3,5-difluoropyridine Chemical compound FC1=CC(F)=CN=C1C1=CC=CC(Br)=C1 HYGFXMKWWQYTEU-UHFFFAOYSA-N 0.000 description 2
• MKMRRLTXILDINF-UHFFFAOYSA-N 2-(3-bromophenyl)-5-fluorobenzonitrile Chemical compound N#CC1=CC(F)=CC=C1C1=CC=CC(Br)=C1 MKMRRLTXILDINF-UHFFFAOYSA-N 0.000 description 2
• BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 2
• YZCNLVQPXKPVCA-UHFFFAOYSA-N 2-(3-hydroxyphenyl)benzonitrile Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)C#N)=C1 YZCNLVQPXKPVCA-UHFFFAOYSA-N 0.000 description 2
• BVDNSIZEMMFBQM-UHFFFAOYSA-N 2-(5-amino-2-fluorophenyl)-3-fluorobenzonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CC=CC=2F)C#N)=C1 BVDNSIZEMMFBQM-UHFFFAOYSA-N 0.000 description 2
• LWWQJVQGRUXCRN-UHFFFAOYSA-N 2-(5-amino-2-fluorophenyl)benzonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CC=CC=2)C#N)=C1 LWWQJVQGRUXCRN-UHFFFAOYSA-N 0.000 description 2
• HGYWGASLLUTRBX-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3,5-difluorobenzonitrile Chemical compound N#CC1=CC(F)=CC(F)=C1C1=CC(Br)=CC=C1F HGYWGASLLUTRBX-UHFFFAOYSA-N 0.000 description 2
• KLIGSLVQWXYJLF-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3,5-difluoropyridine Chemical compound FC1=CC(F)=CN=C1C1=CC(Br)=CC=C1F KLIGSLVQWXYJLF-UHFFFAOYSA-N 0.000 description 2
• MMTSYLQBJKCUQH-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluorobenzonitrile Chemical compound FC1=CC=C(Br)C=C1C1=C(F)C=CC=C1C#N MMTSYLQBJKCUQH-UHFFFAOYSA-N 0.000 description 2
• NQIBQILAMKZKFE-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluoropyridine Chemical compound FC1=CC=C(Br)C=C1C1=NC=CC=C1F NQIBQILAMKZKFE-UHFFFAOYSA-N 0.000 description 2
• RSJWQZOWJGHHJB-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-5-fluoropyridine Chemical compound N1=CC(F)=CC=C1C1=CC(Br)=CC=C1F RSJWQZOWJGHHJB-UHFFFAOYSA-N 0.000 description 2
• ZCQCLNWOJGCXRR-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)pyridine Chemical compound FC1=CC=C(Br)C=C1C1=CC=CC=N1 ZCQCLNWOJGCXRR-UHFFFAOYSA-N 0.000 description 2
• WJUZVFUTJQOBMK-UHFFFAOYSA-N 2-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]-4-fluorobenzonitrile Chemical compound O1CC(C)(C)COB1C1=CC=C(F)C(C=2C(=CC=C(F)C=2)C#N)=C1 WJUZVFUTJQOBMK-UHFFFAOYSA-N 0.000 description 2
• CNKCTXYYABVMLS-UHFFFAOYSA-N 2-amino-3,5-difluorobenzonitrile Chemical compound NC1=C(F)C=C(F)C=C1C#N CNKCTXYYABVMLS-UHFFFAOYSA-N 0.000 description 2
• UNISSOLHERSZOW-UHFFFAOYSA-N 2-amino-3-fluorobenzonitrile Chemical compound NC1=C(F)C=CC=C1C#N UNISSOLHERSZOW-UHFFFAOYSA-N 0.000 description 2
• KDDKQAPQOJGHIK-UHFFFAOYSA-N 2-bromo-3,5-difluorobenzonitrile Chemical compound FC1=CC(F)=C(Br)C(C#N)=C1 KDDKQAPQOJGHIK-UHFFFAOYSA-N 0.000 description 2
• DBECKESJFGWYFN-UHFFFAOYSA-N 2-bromo-3-fluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1Br DBECKESJFGWYFN-UHFFFAOYSA-N 0.000 description 2
• IFGLECYAEGYLSJ-UHFFFAOYSA-N 2-bromo-3-fluoropyridine Chemical compound FC1=CC=CN=C1Br IFGLECYAEGYLSJ-UHFFFAOYSA-N 0.000 description 2
• VMGGIJGQXQEFOC-UHFFFAOYSA-N 2-bromo-5-fluoro-4-(1,2,4-triazol-1-yl)aniline Chemical compound C1=C(Br)C(N)=CC(F)=C1N1N=CN=C1 VMGGIJGQXQEFOC-UHFFFAOYSA-N 0.000 description 2
• HIEJDDTYFMCFKP-UHFFFAOYSA-N 2-bromo-5-fluoro-4-pyrazol-1-ylaniline Chemical compound C1=C(Br)C(N)=CC(F)=C1N1N=CC=C1 HIEJDDTYFMCFKP-UHFFFAOYSA-N 0.000 description 2
• UODINHBLNPPDPD-UHFFFAOYSA-N 2-bromo-5-fluoropyridine Chemical group FC1=CC=C(Br)N=C1 UODINHBLNPPDPD-UHFFFAOYSA-N 0.000 description 2
• LVMOLTGWLVOSSN-UHFFFAOYSA-N 2-chloro-4-(2-fluoro-5-nitrophenyl)pyrimidine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2N=C(Cl)N=CC=2)=C1 LVMOLTGWLVOSSN-UHFFFAOYSA-N 0.000 description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• VDKAKZCOABSWHC-UHFFFAOYSA-N 3,5-difluoro-2-(2-fluoro-5-nitrophenyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC(F)=CC=2F)C#N)=C1 VDKAKZCOABSWHC-UHFFFAOYSA-N 0.000 description 2
• ZUUZNOFTKGDLLN-UHFFFAOYSA-N 3-(1,3,2-dioxaborinan-2-yl)pyridine Chemical compound O1CCCOB1C1=CC=CN=C1 ZUUZNOFTKGDLLN-UHFFFAOYSA-N 0.000 description 2
• FAAZXYYERZEIRZ-UHFFFAOYSA-N 3-(2-chloropyrimidin-4-yl)-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C=2N=C(Cl)N=CC=2)=C1 FAAZXYYERZEIRZ-UHFFFAOYSA-N 0.000 description 2
• HXRXENMBWVGTKY-UHFFFAOYSA-N 3-(2-fluoro-5-nitrophenyl)pyridazine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2N=NC=CC=2)=C1 HXRXENMBWVGTKY-UHFFFAOYSA-N 0.000 description 2
• IJAVHRAPYFEFFS-UHFFFAOYSA-N 3-(3,5-difluoropyridin-2-yl)-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C=2C(=CC(F)=CN=2)F)=C1 IJAVHRAPYFEFFS-UHFFFAOYSA-N 0.000 description 2
• BICKNWBWZQESBL-UHFFFAOYSA-N 3-(3,5-difluoropyridin-2-yl)aniline Chemical compound NC1=CC=CC(C=2C(=CC(F)=CN=2)F)=C1 BICKNWBWZQESBL-UHFFFAOYSA-N 0.000 description 2
• PNVHBUUFMMMKBR-UHFFFAOYSA-N 3-(3-bromophenyl)-1-methylpyrazole Chemical compound CN1C=CC(C=2C=C(Br)C=CC=2)=N1 PNVHBUUFMMMKBR-UHFFFAOYSA-N 0.000 description 2
• JHUIVUBQMBPYJE-UHFFFAOYSA-N 3-(3-bromophenyl)pyridine Chemical compound BrC1=CC=CC(C=2C=NC=CC=2)=C1 JHUIVUBQMBPYJE-UHFFFAOYSA-N 0.000 description 2
• SPSMWBBZLIZCGP-UHFFFAOYSA-N 3-(5-bromo-2-fluorophenyl)pyridazine Chemical compound FC1=CC=C(Br)C=C1C1=CC=CN=N1 SPSMWBBZLIZCGP-UHFFFAOYSA-N 0.000 description 2
• JHYXTDFPLCVQGD-UHFFFAOYSA-N 3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(F)(F)F)C=NN2C=CN=C21 JHYXTDFPLCVQGD-UHFFFAOYSA-N 0.000 description 2
• BNDRWEVUODOUDW-UHFFFAOYSA-N 3-Hydroxy-3-methylbutan-2-one Chemical compound CC(=O)C(C)(C)O BNDRWEVUODOUDW-UHFFFAOYSA-N 0.000 description 2
• DZVQLQJBDDROAN-UHFFFAOYSA-N 3-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-1-methylpyrazole Chemical compound CN1C=CC(C=2C=C(C=CC=2)B2OCC(C)(C)CO2)=N1 DZVQLQJBDDROAN-UHFFFAOYSA-N 0.000 description 2
• OSIWIPBBCIIPCH-UHFFFAOYSA-N 3-fluoro-2-(2-fluoro-5-nitrophenyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC=CC=2F)C#N)=C1 OSIWIPBBCIIPCH-UHFFFAOYSA-N 0.000 description 2
• BWOHRQOZGRVCIP-UHFFFAOYSA-N 3-fluoro-2-(2-fluoro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC=CN=2)F)=C1 BWOHRQOZGRVCIP-UHFFFAOYSA-N 0.000 description 2
• JGEHOZIBWQGIAS-UHFFFAOYSA-N 3-fluoro-2-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(F)C(C=2C(=CC=CC=2F)C#N)=C1 JGEHOZIBWQGIAS-UHFFFAOYSA-N 0.000 description 2
• RYPJPIBQBIHZJB-UHFFFAOYSA-N 3-fluoro-3-methylbutan-2-one Chemical compound CC(=O)C(C)(C)F RYPJPIBQBIHZJB-UHFFFAOYSA-N 0.000 description 2
• VZQVLZBWWQBKFP-UHFFFAOYSA-N 3-fluoro-4-(1,2,4-triazol-1-yl)aniline Chemical compound FC1=CC(N)=CC=C1N1N=CN=C1 VZQVLZBWWQBKFP-UHFFFAOYSA-N 0.000 description 2
• KKRXVEUMRXSOJV-UHFFFAOYSA-N 3-fluoro-4-pyrazol-1-ylaniline Chemical compound FC1=CC(N)=CC=C1N1N=CC=C1 KKRXVEUMRXSOJV-UHFFFAOYSA-N 0.000 description 2
• HUVJUPLHQFUIAY-UHFFFAOYSA-N 3-methylimidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C)C=NN2C=CN=C21 HUVJUPLHQFUIAY-UHFFFAOYSA-N 0.000 description 2
• ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 2
• SLFAHJOSZXTNBQ-UHFFFAOYSA-N 4-(2-fluoro-5-nitrophenyl)pyridazine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C=NN=CC=2)=C1 SLFAHJOSZXTNBQ-UHFFFAOYSA-N 0.000 description 2
• GWEIYNDNRPJYRX-UHFFFAOYSA-N 4-(2-fluoro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C=CN=CC=2)=C1 GWEIYNDNRPJYRX-UHFFFAOYSA-N 0.000 description 2
• KPTUXFWYSABSFG-UHFFFAOYSA-N 4-(2-fluoro-5-nitrophenyl)pyridine-3-carbonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CN=CC=2)C#N)=C1 KPTUXFWYSABSFG-UHFFFAOYSA-N 0.000 description 2
• DWQBEXIVYXPAIE-UHFFFAOYSA-N 4-(2-fluoro-5-nitrophenyl)pyrimidine-5-carbonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CN=CN=2)C#N)=C1 DWQBEXIVYXPAIE-UHFFFAOYSA-N 0.000 description 2
• SVKRUYRFORNEGX-UHFFFAOYSA-N 4-(2-fluorophenyl)pyridine Chemical compound FC1=CC=CC=C1C1=CC=NC=C1 SVKRUYRFORNEGX-UHFFFAOYSA-N 0.000 description 2
• ZHHMJHFENGPAPE-UHFFFAOYSA-N 4-(3-bromophenyl)-1-methyltriazole Chemical compound N1=NN(C)C=C1C1=CC=CC(Br)=C1 ZHHMJHFENGPAPE-UHFFFAOYSA-N 0.000 description 2
• SHRPWJQKIWGZSR-UHFFFAOYSA-N 4-(5-amino-2-fluorophenyl)pyrimidine-5-carbonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CN=CN=2)C#N)=C1 SHRPWJQKIWGZSR-UHFFFAOYSA-N 0.000 description 2
• WHLPEYJBMDVWOJ-UHFFFAOYSA-N 4-(5-bromo-2-fluorophenyl)pyridazine Chemical compound FC1=CC=C(Br)C=C1C1=CC=NN=C1 WHLPEYJBMDVWOJ-UHFFFAOYSA-N 0.000 description 2
• SUYFLHOJQQTXAO-UHFFFAOYSA-N 4-(5-bromo-2-fluorophenyl)pyridine Chemical compound FC1=CC=C(Br)C=C1C1=CC=NC=C1 SUYFLHOJQQTXAO-UHFFFAOYSA-N 0.000 description 2
• UFJQVVMLHWZXGK-UHFFFAOYSA-N 4-(5-bromo-2-fluorophenyl)pyridine-3-carbonitrile Chemical compound FC1=CC=C(Br)C=C1C1=CC=NC=C1C#N UFJQVVMLHWZXGK-UHFFFAOYSA-N 0.000 description 2
• RUOQKIAQVJYBTN-UHFFFAOYSA-N 4-(5-bromo-2-fluorophenyl)pyrimidine Chemical compound FC1=CC=C(Br)C=C1C1=CC=NC=N1 RUOQKIAQVJYBTN-UHFFFAOYSA-N 0.000 description 2
• HENGIOQBVQBVJZ-UHFFFAOYSA-N 4-(5-bromo-2-fluorophenyl)pyrimidine-5-carbonitrile Chemical compound FC1=CC=C(Br)C=C1C1=NC=NC=C1C#N HENGIOQBVQBVJZ-UHFFFAOYSA-N 0.000 description 2
• YNNRYPNJCONEGQ-UHFFFAOYSA-N 4-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]pyrimidine-5-carboxamide Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=NC=NC=C1C(N)=O YNNRYPNJCONEGQ-UHFFFAOYSA-N 0.000 description 2
• TUWIDKLZDCNLFH-UHFFFAOYSA-N 4-bromo-1-fluoro-2-(2-methylsulfonylphenyl)benzene Chemical group CS(=O)(=O)C1=CC=CC=C1C1=CC(Br)=CC=C1F TUWIDKLZDCNLFH-UHFFFAOYSA-N 0.000 description 2
• WKYVGBPCXOPWEA-UHFFFAOYSA-N 4-bromopyridine-3-carbaldehyde Chemical compound BrC1=CC=NC=C1C=O WKYVGBPCXOPWEA-UHFFFAOYSA-N 0.000 description 2
• DMQBJRMKGVMOHX-UHFFFAOYSA-N 4-bromopyridine-3-carbonitrile Chemical compound BrC1=CC=NC=C1C#N DMQBJRMKGVMOHX-UHFFFAOYSA-N 0.000 description 2
• GIDRQXIETGYXLF-UHFFFAOYSA-N 4-fluoro-3-(3-fluoropyridin-2-yl)aniline Chemical compound NC1=CC=C(F)C(C=2C(=CC=CN=2)F)=C1 GIDRQXIETGYXLF-UHFFFAOYSA-N 0.000 description 2
• DWRSJDMYSRHFPN-UHFFFAOYSA-N 4-fluoro-3-(5-fluoropyridin-2-yl)aniline Chemical compound NC1=CC=C(F)C(C=2N=CC(F)=CC=2)=C1 DWRSJDMYSRHFPN-UHFFFAOYSA-N 0.000 description 2
• NFDGPWIQYGUYLS-UHFFFAOYSA-N 4-fluoro-3-pyridazin-3-ylaniline Chemical compound NC1=CC=C(F)C(C=2N=NC=CC=2)=C1 NFDGPWIQYGUYLS-UHFFFAOYSA-N 0.000 description 2
• FHGCTGAFBLHETD-UHFFFAOYSA-N 4-fluoro-3-pyridazin-4-ylaniline Chemical compound NC1=CC=C(F)C(C=2C=NN=CC=2)=C1 FHGCTGAFBLHETD-UHFFFAOYSA-N 0.000 description 2
• ZMTHKQVZVGZICL-UHFFFAOYSA-N 4-fluoro-3-pyridin-2-ylaniline Chemical compound NC1=CC=C(F)C(C=2N=CC=CC=2)=C1 ZMTHKQVZVGZICL-UHFFFAOYSA-N 0.000 description 2
• RGFAOBXVEJMYRE-UHFFFAOYSA-N 4-fluoro-3-pyridin-4-ylaniline Chemical compound NC1=CC=C(F)C(C=2C=CN=CC=2)=C1 RGFAOBXVEJMYRE-UHFFFAOYSA-N 0.000 description 2
• PFJASDQGDUHSNJ-UHFFFAOYSA-N 4-fluoro-3-pyrimidin-4-ylaniline Chemical compound NC1=CC=C(F)C(C=2N=CN=CC=2)=C1 PFJASDQGDUHSNJ-UHFFFAOYSA-N 0.000 description 2
• RQUTXSABMPDXJA-UHFFFAOYSA-N 5-(2-fluoropropan-2-yl)-1,2,4-triazin-3-amine Chemical compound CC(C)(F)C1=CN=NC(N)=N1 RQUTXSABMPDXJA-UHFFFAOYSA-N 0.000 description 2
• YZRJEJLXEXGHOQ-UHFFFAOYSA-N 5-(3-bromophenyl)-1-methyl-1,2,4-triazole Chemical compound CN1N=CN=C1C1=CC=CC(Br)=C1 YZRJEJLXEXGHOQ-UHFFFAOYSA-N 0.000 description 2
• CCOOLPDVTMMYJW-UHFFFAOYSA-N 5-(3-bromophenyl)-1-methyltriazole Chemical compound CN1N=NC=C1C1=CC=CC(Br)=C1 CCOOLPDVTMMYJW-UHFFFAOYSA-N 0.000 description 2
• MVQPQHSCRMQGDV-UHFFFAOYSA-N 5-fluoro-2-(2-fluoro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2N=CC(F)=CC=2)=C1 MVQPQHSCRMQGDV-UHFFFAOYSA-N 0.000 description 2
• VWQLSVVMTODAAH-UHFFFAOYSA-N 5-fluoro-2-(3-nitrophenyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC=CC(C=2C(=CC(F)=CC=2)C#N)=C1 VWQLSVVMTODAAH-UHFFFAOYSA-N 0.000 description 2
• WLRMLHUPLFXRAY-UHFFFAOYSA-N 5-fluoro-2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(C=2C(=CC(F)=CC=2)C#N)=C1 WLRMLHUPLFXRAY-UHFFFAOYSA-N 0.000 description 2
• RMISJEHRCNTDKY-UHFFFAOYSA-N 7-bromo-3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(C)(F)C)C=NN2C(Br)=CN=C21 RMISJEHRCNTDKY-UHFFFAOYSA-N 0.000 description 2
• PZCKDEHMWFMSLF-UHFFFAOYSA-N 7-bromo-3-tert-butylimidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(C)(C)C)C=NN2C(Br)=CN=C21 PZCKDEHMWFMSLF-UHFFFAOYSA-N 0.000 description 2
• 208000008811 Agoraphobia Diseases 0.000 description 2
• 208000020925 Bipolar disease Diseases 0.000 description 2
• 108020004635 Complementary DNA Proteins 0.000 description 2
• 206010012218 Delirium Diseases 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
• 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 2
• AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
• 229920001410 Microfiber Polymers 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
• PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 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
• PODKTOWRSBFDPR-UHFFFAOYSA-N [3-(2-cyanophenyl)-2-fluorophenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C=2C(=CC=CC=2)C#N)=C1F PODKTOWRSBFDPR-UHFFFAOYSA-N 0.000 description 2
• BJGLVVHRQKYHQY-UHFFFAOYSA-N [3-(2-cyanophenyl)phenyl] trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC(C=2C(=CC=CC=2)C#N)=C1 BJGLVVHRQKYHQY-UHFFFAOYSA-N 0.000 description 2
• DRFOEFJNMLJZMB-UHFFFAOYSA-N [3-(3,5-difluoropyridin-2-yl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C=2C(=CC(F)=CN=2)F)=C1 DRFOEFJNMLJZMB-UHFFFAOYSA-N 0.000 description 2
• UHPNWGKYLBZTKQ-UHFFFAOYSA-N [4-fluoro-3-(1,2,4-triazol-1-yl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(F)C(N2N=CN=C2)=C1 UHPNWGKYLBZTKQ-UHFFFAOYSA-N 0.000 description 2
• MUBVHFXIZHDEGM-UHFFFAOYSA-N [4-fluoro-3-(3-fluoropyridin-2-yl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2C(=CC=CN=2)F)=C1 MUBVHFXIZHDEGM-UHFFFAOYSA-N 0.000 description 2
• MQLCTVVZKOTTNU-UHFFFAOYSA-N [4-fluoro-3-(5-fluoropyridin-2-yl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2N=CC(F)=CC=2)=C1 MQLCTVVZKOTTNU-UHFFFAOYSA-N 0.000 description 2
• KGYOJJZYYNSMDH-UHFFFAOYSA-N [5-(2-fluoro-5-nitrophenyl)pyridazin-4-yl]-trimethylsilane Chemical compound C[Si](C)(C)C1=CN=NC=C1C1=CC([N+]([O-])=O)=CC=C1F KGYOJJZYYNSMDH-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 2
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 2
• OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 2
• 125000005805 dimethoxy phenyl group Chemical group 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 238000001839 endoscopy Methods 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• 229960002200 flunitrazepam Drugs 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 125000001207 fluorophenyl group Chemical group 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 150000002443 hydroxylamines Chemical class 0.000 description 2
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000005567 liquid scintillation counting Methods 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 239000003658 microfiber Substances 0.000 description 2
• SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 208000019906 panic disease Diseases 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
• IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 2
• 229910052705 radium Inorganic materials 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 229910052701 rubidium Inorganic materials 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 229940087562 sodium acetate trihydrate Drugs 0.000 description 2
• 229940079827 sodium hydrogen sulfite Drugs 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 238000000638 solvent extraction Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 201000009032 substance abuse Diseases 0.000 description 2
• 231100000736 substance abuse Toxicity 0.000 description 2
• 208000011117 substance-related disease Diseases 0.000 description 2
• 239000001117 sulphuric acid Substances 0.000 description 2
• 235000011149 sulphuric acid Nutrition 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 229960001367 tartaric acid Drugs 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
• 239000012414 tert-butyl nitrite Substances 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 238000001665 trituration Methods 0.000 description 2
• 238000000825 ultraviolet detection Methods 0.000 description 2
• 239000011592 zinc chloride Substances 0.000 description 2
• 235000005074 zinc chloride Nutrition 0.000 description 2
• YUHZIUAREWNXJT-UHFFFAOYSA-N (2-fluoropyridin-3-yl)boronic acid Chemical class OB(O)C1=CC=CN=C1F YUHZIUAREWNXJT-UHFFFAOYSA-N 0.000 description 1
• QXBWTYBCNFKURT-UHFFFAOYSA-N (2-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=CC=C1B(O)O QXBWTYBCNFKURT-UHFFFAOYSA-N 0.000 description 1
• CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
• XAEOVQODHLLNKX-UHFFFAOYSA-N (3-aminophenyl)boronic acid;hydrate Chemical compound O.NC1=CC=CC(B(O)O)=C1 XAEOVQODHLLNKX-UHFFFAOYSA-N 0.000 description 1
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
• KUUJEDBTCVDYGA-UHFFFAOYSA-N 1,1-dibromo-3,3-difluorobutan-2-one Chemical compound CC(F)(F)C(=O)C(Br)Br KUUJEDBTCVDYGA-UHFFFAOYSA-N 0.000 description 1
• WIPDATICDHNWKG-UHFFFAOYSA-N 1,1-dibromo-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)C(Br)Br WIPDATICDHNWKG-UHFFFAOYSA-N 0.000 description 1
• RJBREFRROKJBEP-UHFFFAOYSA-N 1,1-dibromo-3-fluoro-3-methylbutan-2-one Chemical compound CC(C)(F)C(=O)C(Br)Br RJBREFRROKJBEP-UHFFFAOYSA-N 0.000 description 1
• GKTJJLMMPHCKLM-UHFFFAOYSA-N 1,1-dibromo-3-hydroxy-3-methylbutan-2-one Chemical compound CC(C)(O)C(=O)C(Br)Br GKTJJLMMPHCKLM-UHFFFAOYSA-N 0.000 description 1
• 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 1
• MJIWQHRXSLOUJN-UHFFFAOYSA-N 1,2,4-triazin-3-amine Chemical compound NC1=NC=CN=N1 MJIWQHRXSLOUJN-UHFFFAOYSA-N 0.000 description 1
• JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 1
• IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
• UOFUBNTXICKJOP-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)imidazole Chemical compound [O-][N+](=O)C1=CC=C(F)C(N2C=NC=C2)=C1 UOFUBNTXICKJOP-UHFFFAOYSA-N 0.000 description 1
• BBTAHCQEABZCRU-UHFFFAOYSA-N 1-(5-bromo-2-fluorophenyl)imidazole Chemical compound FC1=CC=C(Br)C=C1N1C=NC=C1 BBTAHCQEABZCRU-UHFFFAOYSA-N 0.000 description 1
• LFARAYXKOYUULQ-UHFFFAOYSA-N 1-(5-bromo-2-fluorophenyl)pyrazole Chemical compound FC1=CC=C(Br)C=C1N1N=CC=C1 LFARAYXKOYUULQ-UHFFFAOYSA-N 0.000 description 1
• DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 description 1
• RTQGOPPPIVEJAH-UHFFFAOYSA-N 1-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-1,2,4-triazole Chemical compound O1CC(C)(C)COB1C1=CC=CC(N2N=CN=C2)=C1 RTQGOPPPIVEJAH-UHFFFAOYSA-N 0.000 description 1
• FVAPDXJYJZZGAD-UHFFFAOYSA-N 1-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]imidazole Chemical compound O1CC(C)(C)COB1C1=CC=C(F)C(N2C=NC=C2)=C1 FVAPDXJYJZZGAD-UHFFFAOYSA-N 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000004293 19F NMR spectroscopy Methods 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• MMPKVFQMDMBXSG-UHFFFAOYSA-N 2,3,5-trifluorobenzonitrile Chemical compound FC1=CC(F)=C(F)C(C#N)=C1 MMPKVFQMDMBXSG-UHFFFAOYSA-N 0.000 description 1
• GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 1
• BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 1
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
• ITDZQHLCVJLENK-UHFFFAOYSA-N 2-(3-aminophenyl)-5-fluorobenzonitrile Chemical compound NC1=CC=CC(C=2C(=CC(F)=CC=2)C#N)=C1 ITDZQHLCVJLENK-UHFFFAOYSA-N 0.000 description 1
• WAEWRICTVAIONI-UHFFFAOYSA-N 2-(4-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C1=C(F)C(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 WAEWRICTVAIONI-UHFFFAOYSA-N 0.000 description 1
• XYNNZCLMDQOUQD-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(C=2C(=CC=C(Br)C=2)F)=C1 XYNNZCLMDQOUQD-UHFFFAOYSA-N 0.000 description 1
• ACAUOIRLAOQTOD-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)benzonitrile Chemical compound FC1=CC=C(Br)C=C1C1=CC=CC=C1C#N ACAUOIRLAOQTOD-UHFFFAOYSA-N 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• BYQYZJZHTASOKS-UHFFFAOYSA-N 2-[5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-fluorophenyl]-3,5-difluorobenzonitrile Chemical compound O1CC(C)(C)COB1C1=CC=C(F)C(C=2C(=CC(F)=CC=2F)C#N)=C1 BYQYZJZHTASOKS-UHFFFAOYSA-N 0.000 description 1
• XXCGNJISZTZOJB-UHFFFAOYSA-N 2-[7-(4-fluoro-3-pyridazin-4-ylphenyl)imidazo[1,2-b][1,2,4]triazin-3-yl]propan-2-ol Chemical compound C=1N=C2N=C(C(C)(O)C)C=NN2C=1C(C=1)=CC=C(F)C=1C1=CC=NN=C1 XXCGNJISZTZOJB-UHFFFAOYSA-N 0.000 description 1
• QENVELOEJXDOGZ-UHFFFAOYSA-N 2-[[5-(3-bromophenyl)-1,2,4-triazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1N=CN=C1C1=CC=CC(Br)=C1 QENVELOEJXDOGZ-UHFFFAOYSA-N 0.000 description 1
• SDAANRAUZVUVCU-UHFFFAOYSA-N 2-[[5-(3-bromophenyl)triazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1N=NC=C1C1=CC=CC(Br)=C1 SDAANRAUZVUVCU-UHFFFAOYSA-N 0.000 description 1
• CGTVUAQWGSZCFH-UHFFFAOYSA-N 2-bromo-1-chloro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(Br)=C1 CGTVUAQWGSZCFH-UHFFFAOYSA-N 0.000 description 1
• MNNDREXLRLDWEY-UHFFFAOYSA-N 2-bromo-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(Br)=C1 MNNDREXLRLDWEY-UHFFFAOYSA-N 0.000 description 1
• MDHNVHCZDCSTMS-UHFFFAOYSA-N 2-bromo-5-fluorobenzonitrile Chemical compound FC1=CC=C(Br)C(C#N)=C1 MDHNVHCZDCSTMS-UHFFFAOYSA-N 0.000 description 1
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
• MLEQIXZRKQKXST-UHFFFAOYSA-N 2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenol Chemical compound C1=C(F)C(O)=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 MLEQIXZRKQKXST-UHFFFAOYSA-N 0.000 description 1
• KJVBJICWGQIMOZ-UHFFFAOYSA-N 2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1F KJVBJICWGQIMOZ-UHFFFAOYSA-N 0.000 description 1
• OOIAKFJDLQEPOF-UHFFFAOYSA-N 2-fluoro-6-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzonitrile Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(C=2C(=C(F)C=CC=2)C#N)=C1 OOIAKFJDLQEPOF-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
• DRSZTATWOSZRAK-UHFFFAOYSA-N 3,4-dibromobutan-2-one Chemical compound CC(=O)C(Br)CBr DRSZTATWOSZRAK-UHFFFAOYSA-N 0.000 description 1
• JWPMJAUVXVVXSZ-UHFFFAOYSA-N 3-(1,1-difluoroethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(F)(F)C)C=NN2C=CN=C21 JWPMJAUVXVVXSZ-UHFFFAOYSA-N 0.000 description 1
• RPYYBYCECVSTKP-UHFFFAOYSA-N 3-(2-chloro-5-nitrophenyl)pyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=2C=NC=CC=2)=C1 RPYYBYCECVSTKP-UHFFFAOYSA-N 0.000 description 1
• KLHKVGWYCUJXRS-UHFFFAOYSA-N 3-(2-fluoropropan-2-yl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(C)(F)C)C=NN2C=CN=C21 KLHKVGWYCUJXRS-UHFFFAOYSA-N 0.000 description 1
• AQSFZAKLNQTABN-UHFFFAOYSA-N 3-(5-bromo-2-chlorophenyl)pyridine Chemical compound ClC1=CC=C(Br)C=C1C1=CC=CN=C1 AQSFZAKLNQTABN-UHFFFAOYSA-N 0.000 description 1
• ZGHFDIIVVIFNPS-UHFFFAOYSA-N 3-Methyl-3-buten-2-one Chemical compound CC(=C)C(C)=O ZGHFDIIVVIFNPS-UHFFFAOYSA-N 0.000 description 1
• ZHBFFXCZBSWUST-UHFFFAOYSA-N 3-[2-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]pyridine Chemical compound O1CC(C)(C)COB1C1=CC=C(Cl)C(C=2C=NC=CC=2)=C1 ZHBFFXCZBSWUST-UHFFFAOYSA-N 0.000 description 1
• VRHDKPFAGWJQJW-UHFFFAOYSA-N 3-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-1-methyl-1,2,4-triazole Chemical compound CN1C=NC(C=2C=C(C=CC=2)B2OCC(C)(C)CO2)=N1 VRHDKPFAGWJQJW-UHFFFAOYSA-N 0.000 description 1
• LFHJGDVGEUUVDD-UHFFFAOYSA-N 3-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]pyridine Chemical compound O1CC(C)(C)COB1C1=CC=CC(C=2C=NC=CC=2)=C1 LFHJGDVGEUUVDD-UHFFFAOYSA-N 0.000 description 1
• TZFJJBXKRJVBPX-UHFFFAOYSA-N 3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]aniline Chemical compound NC1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 TZFJJBXKRJVBPX-UHFFFAOYSA-N 0.000 description 1
• XHCWDDGZFBAXRT-UHFFFAOYSA-N 3-bromo-3-methylbutan-2-one Chemical compound CC(=O)C(C)(C)Br XHCWDDGZFBAXRT-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• IBWYHNOFSKJKKY-UHFFFAOYSA-N 3-chloropyridazine Chemical compound ClC1=CC=CN=N1 IBWYHNOFSKJKKY-UHFFFAOYSA-N 0.000 description 1
• PWGQRWCRGIHOKN-UHFFFAOYSA-N 3-methyl-5-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]-1,2,4-oxadiazole Chemical compound CC1=NOC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 PWGQRWCRGIHOKN-UHFFFAOYSA-N 0.000 description 1
• MUNOBADFTHUUFG-UHFFFAOYSA-N 3-phenylaniline Chemical compound NC1=CC=CC(C=2C=CC=CC=2)=C1 MUNOBADFTHUUFG-UHFFFAOYSA-N 0.000 description 1
• BKJXSQXZIOTRTP-UHFFFAOYSA-N 4-(3-bromophenyl)-2h-triazole Chemical compound BrC1=CC=CC(C2=NNN=C2)=C1 BKJXSQXZIOTRTP-UHFFFAOYSA-N 0.000 description 1
• PCPGXOIRNPEXDW-UHFFFAOYSA-N 4-(5-amino-2-fluorophenyl)pyridine-3-carbonitrile Chemical compound NC1=CC=C(F)C(C=2C(=CN=CC=2)C#N)=C1 PCPGXOIRNPEXDW-UHFFFAOYSA-N 0.000 description 1
• RPVKFOWUQNUEHF-UHFFFAOYSA-N 4-[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(F)C(C=2C=CN=CC=2)=C1 RPVKFOWUQNUEHF-UHFFFAOYSA-N 0.000 description 1
• LUIHGLZZNUHXAF-UHFFFAOYSA-N 4-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-2-methyltriazole Chemical compound CN1N=CC(C=2C=C(C=CC=2)B2OCC(C)(C)CO2)=N1 LUIHGLZZNUHXAF-UHFFFAOYSA-N 0.000 description 1
• DQYAZOUZZJBDOL-UHFFFAOYSA-N 4-[3-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]thiadiazole Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CSN=N1 DQYAZOUZZJBDOL-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• OOYJCQNLFPKLBX-UHFFFAOYSA-N 4-bromo-1-fluoro-2-(2-methylsulfanylphenyl)benzene Chemical group CSC1=CC=CC=C1C1=CC(Br)=CC=C1F OOYJCQNLFPKLBX-UHFFFAOYSA-N 0.000 description 1
• SEVMQEIGENUPIE-UHFFFAOYSA-N 4-bromo-1-fluoro-2-methoxybenzene Chemical compound COC1=CC(Br)=CC=C1F SEVMQEIGENUPIE-UHFFFAOYSA-N 0.000 description 1
• MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 1
• ZECCDLLQKKWPCG-UHFFFAOYSA-N 4-chloro-3-pyridin-3-ylaniline Chemical compound NC1=CC=C(Cl)C(C=2C=NC=CC=2)=C1 ZECCDLLQKKWPCG-UHFFFAOYSA-N 0.000 description 1
• ZVJJQADVZUHQTR-UHFFFAOYSA-N 4-chloropyrimidine-5-carbonitrile Chemical compound ClC1=NC=NC=C1C#N ZVJJQADVZUHQTR-UHFFFAOYSA-N 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• LSGVEKDEHAZPAK-UHFFFAOYSA-N 5-(1,1-difluoroethyl)-1,2,4-triazin-3-amine Chemical compound CC(F)(F)C1=CN=NC(N)=N1 LSGVEKDEHAZPAK-UHFFFAOYSA-N 0.000 description 1
• RIYUQLBSAMXENJ-UHFFFAOYSA-N 5-(3-bromophenyl)-1-methylpyrazole Chemical compound CN1N=CC=C1C1=CC=CC(Br)=C1 RIYUQLBSAMXENJ-UHFFFAOYSA-N 0.000 description 1
• SSHMLGQRBZYTMM-UHFFFAOYSA-N 5-(3-bromophenyl)-1h-1,2,4-triazole Chemical compound BrC1=CC=CC(C2=NNC=N2)=C1 SSHMLGQRBZYTMM-UHFFFAOYSA-N 0.000 description 1
• NVRXIZHZQPRBKL-UHFFFAOYSA-N 5-(3-bromophenyl)-1h-pyrazole Chemical compound BrC1=CC=CC(C=2NN=CC=2)=C1 NVRXIZHZQPRBKL-UHFFFAOYSA-N 0.000 description 1
• ZXANZZMXMLJAGF-UHFFFAOYSA-N 5-fluoro-2-(2-fluoro-5-nitrophenyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=2C(=CC(F)=CC=2)C#N)=C1 ZXANZZMXMLJAGF-UHFFFAOYSA-N 0.000 description 1
• XJNSJYUPFYNAMU-UHFFFAOYSA-N 5-methyl-1,2,4-triazin-3-amine Chemical compound CC1=CN=NC(N)=N1 XJNSJYUPFYNAMU-UHFFFAOYSA-N 0.000 description 1
• DLIPZMXRDYIYHK-UHFFFAOYSA-N 6-methyl-1,2,4-triazin-3-amine Chemical compound CC1=CN=C(N)N=N1 DLIPZMXRDYIYHK-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• MHDMKOLJRLORCW-UHFFFAOYSA-N 7-(2-fluoro-3-pyridin-4-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound FC1=C(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)C=CC=C1C1=CC=NC=C1 MHDMKOLJRLORCW-UHFFFAOYSA-N 0.000 description 1
• BONFPQLOXKVPIA-UHFFFAOYSA-N 7-(3-pyrazin-2-ylphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C=1N=C2N=C(C(F)(F)F)C=NN2C=1C(C=1)=CC=CC=1C1=CN=CC=N1 BONFPQLOXKVPIA-UHFFFAOYSA-N 0.000 description 1
• SRICMDNLGWPNBJ-UHFFFAOYSA-N 7-(4-fluoro-3-methoxyphenyl)-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=C(F)C(OC)=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 SRICMDNLGWPNBJ-UHFFFAOYSA-N 0.000 description 1
• FYNZTDAJDIAOBJ-UHFFFAOYSA-N 7-[3-(1-ethylpyrazol-3-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound CCN1C=CC(C=2C=C(C=CC=2)C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=N1 FYNZTDAJDIAOBJ-UHFFFAOYSA-N 0.000 description 1
• SWBUEHULLUZEGU-UHFFFAOYSA-N 7-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-4-fluorophenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound O1CC(C)(C)COB1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F SWBUEHULLUZEGU-UHFFFAOYSA-N 0.000 description 1
• MGVMOQWJDROOOQ-UHFFFAOYSA-N 7-[3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound O1CC(C)(C)COB1C1=CC=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=C1 MGVMOQWJDROOOQ-UHFFFAOYSA-N 0.000 description 1
• VYNWMAODWXAKMQ-UHFFFAOYSA-N 7-[4-fluoro-3-(4-fluorophenyl)phenyl]-3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound C1=CC(F)=CC=C1C1=CC(C=2N3N=CC(=NC3=NC=2)C(F)(F)F)=CC=C1F VYNWMAODWXAKMQ-UHFFFAOYSA-N 0.000 description 1
• NNZBAOLLCAKLMZ-UHFFFAOYSA-N 7-bromo-2-methylimidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C)C=NC2=NC=C(Br)N21 NNZBAOLLCAKLMZ-UHFFFAOYSA-N 0.000 description 1
• NMKZRKGYKXUAIE-UHFFFAOYSA-N 7-bromo-3-(1,1-difluoroethyl)imidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C(F)(F)C)C=NN2C(Br)=CN=C21 NMKZRKGYKXUAIE-UHFFFAOYSA-N 0.000 description 1
• VVYDIUYRSRLWOA-UHFFFAOYSA-N 7-bromo-3-methylimidazo[1,2-b][1,2,4]triazine Chemical compound N1=C(C)C=NN2C(Br)=CN=C21 VVYDIUYRSRLWOA-UHFFFAOYSA-N 0.000 description 1
• JYJSSOBJHVIBLL-UHFFFAOYSA-N 7-bromoimidazo[1,2-b][1,2,4]triazine Chemical compound N1=CC=NN2C(Br)=CN=C21 JYJSSOBJHVIBLL-UHFFFAOYSA-N 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
• 208000031091 Amnestic disease Diseases 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 206010002650 Anorexia nervosa and bulimia Diseases 0.000 description 1
• 241001553178 Arachis glabrata Species 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
• 239000005711 Benzoic acid Substances 0.000 description 1
• SLZOVPXINDAHQN-UHFFFAOYSA-N BrC1=C(C#N)C=C(C=C1)F.C=1(C(=CC=CC1)C#N)C1=CC=CC=C1 Chemical compound BrC1=C(C#N)C=C(C=C1)F.C=1(C(=CC=CC1)C#N)C1=CC=CC=C1 SLZOVPXINDAHQN-UHFFFAOYSA-N 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
• FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 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
• 206010012239 Delusion Diseases 0.000 description 1
• 206010012374 Depressed mood Diseases 0.000 description 1
• 208000020401 Depressive disease Diseases 0.000 description 1
• 229920002307 Dextran Polymers 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
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 208000030814 Eating disease Diseases 0.000 description 1
• IOOOHXNVEYMMLI-UHFFFAOYSA-N FC1=C(C=C(C=C1)[N+](=O)[O-])C1=C(C#N)C=CC=N1.NC=1C=CC(=C(C1)C1=C(C#N)C=CC=N1)F Chemical compound FC1=C(C=C(C=C1)[N+](=O)[O-])C1=C(C#N)C=CC=N1.NC=1C=CC(=C(C1)C1=C(C#N)C=CC=N1)F IOOOHXNVEYMMLI-UHFFFAOYSA-N 0.000 description 1
• KSFYQRCYAUBSTO-UHFFFAOYSA-N FC1=CC=C(C(=C1)C1=C(C=CC(=C1)[N+](=O)[O-])F)C#N.NC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F Chemical compound FC1=CC=C(C(=C1)C1=C(C=CC(=C1)[N+](=O)[O-])F)C#N.NC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F KSFYQRCYAUBSTO-UHFFFAOYSA-N 0.000 description 1
• 208000019454 Feeding and Eating disease Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 208000016621 Hearing disease Diseases 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 238000012347 Morris Water Maze Methods 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000007101 Muscle Cramp Diseases 0.000 description 1
• 208000008238 Muscle Spasticity Diseases 0.000 description 1
• NTYONGHUFLKKOR-UHFFFAOYSA-N NC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F.BrC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F Chemical compound NC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F.BrC=1C=CC(=C(C1)C=1C(=CC=C(C1)F)C#N)F NTYONGHUFLKKOR-UHFFFAOYSA-N 0.000 description 1
• 229910003827 NRaRb Inorganic materials 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 206010033892 Paraplegia Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
• 208000031649 Postoperative Nausea and Vomiting Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 206010036618 Premenstrual syndrome Diseases 0.000 description 1
• 208000028017 Psychotic disease Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 206010041250 Social phobia Diseases 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000013200 Stress disease Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000003028 Stuttering Diseases 0.000 description 1
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 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 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 239000005864 Sulphur Substances 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
• SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
• 208000009205 Tinnitus Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
• 206010046543 Urinary incontinence Diseases 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• YKOWBJJOJNGCAD-SHYZEUOFSA-N [(2r,3s,5r)-3-hydroxy-5-[4-(hydroxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl dihydrogen phosphate Chemical compound O=C1N=C(NO)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 YKOWBJJOJNGCAD-SHYZEUOFSA-N 0.000 description 1
• UNMGYCJAYWILIW-UHFFFAOYSA-N [2-fluoro-5-[3-(trifluoromethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl] trifluoromethanesulfonate Chemical compound C1=C(OS(=O)(=O)C(F)(F)F)C(F)=CC=C1C1=CN=C2N1N=CC(C(F)(F)F)=N2 UNMGYCJAYWILIW-UHFFFAOYSA-N 0.000 description 1
• MKHCEYUAQNIFHH-UHFFFAOYSA-N [3-(3-cyanopyridin-2-yl)-4-fluorophenyl]boronic acid Chemical compound OB(O)C1=CC=C(F)C(C=2C(=CC=CN=2)C#N)=C1 MKHCEYUAQNIFHH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 208000026345 acute stress disease Diseases 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 208000014646 age-related hearing impairment Diseases 0.000 description 1
• 208000029650 alcohol withdrawal Diseases 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000005530 alkylenedioxy group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• JRTIDHTUMYMPRU-UHFFFAOYSA-N alpidem Chemical compound N1=C2C=CC(Cl)=CN2C(CC(=O)N(CCC)CCC)=C1C1=CC=C(Cl)C=C1 JRTIDHTUMYMPRU-UHFFFAOYSA-N 0.000 description 1
• 229950008673 alpidem Drugs 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 238000001949 anaesthesia Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000000454 anti-cipatory effect Effects 0.000 description 1
• 230000001773 anti-convulsant effect Effects 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 229960003965 antiepileptics Drugs 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000005199 aryl carbonyloxy group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
• 229940090047 auto-injector Drugs 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 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
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 230000027288 circadian rhythm Effects 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 208000026725 cyclothymic disease Diseases 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 231100000868 delusion Toxicity 0.000 description 1
• 230000003001 depressive effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229960003529 diazepam Drugs 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
• FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 235000014632 disordered eating Nutrition 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 208000024732 dysthymic disease Diseases 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000001493 electron microscopy Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• ISVLDAIKRGXNCZ-UHFFFAOYSA-N ethyl 2,2-difluoropropanoate Chemical compound CCOC(=O)C(C)(F)F ISVLDAIKRGXNCZ-UHFFFAOYSA-N 0.000 description 1
• FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 239000003326 hypnotic agent Substances 0.000 description 1
• 230000000147 hypnotic effect Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 1
• 125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 208000024714 major depressive disease Diseases 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000006996 mental state Effects 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 201000003152 motion sickness Diseases 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 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
• 239000013110 organic ligand Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 230000036407 pain Effects 0.000 description 1
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229960005152 pentetrazol Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 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
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229910003446 platinum oxide Inorganic materials 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 208000028173 post-traumatic stress disease Diseases 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000009101 premedication Methods 0.000 description 1
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 238000000611 regression analysis Methods 0.000 description 1
• 239000011369 resultant mixture Substances 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000020341 sensory perception of pain Effects 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
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 208000027765 speech disease Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960003188 temazepam Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
• 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 231100000886 tinnitus Toxicity 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 208000018726 traumatic encephalopathy Diseases 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 1
• WUOFQGMXQCSPPV-UHFFFAOYSA-N tributyl(1,3-thiazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CS1 WUOFQGMXQCSPPV-UHFFFAOYSA-N 0.000 description 1
• GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
• UNEPXPMBVGDXGH-UHFFFAOYSA-N tributyl(pyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1 UNEPXPMBVGDXGH-UHFFFAOYSA-N 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
• DHWQQVXDRKXOCV-UHFFFAOYSA-N trimethyl-[2-(1,2,4-triazol-1-ylmethoxy)ethyl]silane Chemical compound C[Si](C)(C)CCOCN1C=NC=N1 DHWQQVXDRKXOCV-UHFFFAOYSA-N 0.000 description 1
• RZLMQJSSMROKSS-UHFFFAOYSA-N trimethyl-[2-(triazol-1-ylmethoxy)ethyl]silane Chemical compound C[Si](C)(C)CCOCN1C=CN=N1 RZLMQJSSMROKSS-UHFFFAOYSA-N 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 229960001475 zolpidem Drugs 0.000 description 1
• ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1