KR20070107037A - 선택적 5ht2a 길항제로서의 치환된 비스 아릴 및헤테로아릴 화합물 - Google Patents
선택적 5ht2a 길항제로서의 치환된 비스 아릴 및헤테로아릴 화합물 Download PDFInfo
- Publication number
- KR20070107037A KR20070107037A KR1020077018430A KR20077018430A KR20070107037A KR 20070107037 A KR20070107037 A KR 20070107037A KR 1020077018430 A KR1020077018430 A KR 1020077018430A KR 20077018430 A KR20077018430 A KR 20077018430A KR 20070107037 A KR20070107037 A KR 20070107037A
- Authority
- KR
- South Korea
- Prior art keywords
- fluoro
- benzyl
- methyl
- phenyl
- ylmethyl
- Prior art date
- 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.)
- Withdrawn
Links
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 46
- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 43
- 239000005557 antagonist Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 166
- 208000019116 sleep disease Diseases 0.000 claims abstract description 48
- -1 thiophenylcarbonyl Chemical group 0.000 claims description 475
- 125000000217 alkyl group Chemical group 0.000 claims description 173
- 239000000203 mixture Substances 0.000 claims description 139
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 100
- 229910052757 nitrogen Inorganic materials 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 125000001544 thienyl group Chemical group 0.000 claims description 42
- 125000002541 furyl group Chemical group 0.000 claims description 41
- 125000004076 pyridyl group Chemical group 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000004193 piperazinyl group Chemical group 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 22
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- 206010022437 insomnia Diseases 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 21
- 230000003287 optical effect Effects 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 125000003386 piperidinyl group Chemical group 0.000 claims description 17
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 16
- 125000006332 fluoro benzoyl group Chemical group 0.000 claims description 16
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 16
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000005605 benzo group Chemical group 0.000 claims description 13
- 208000001797 obstructive sleep apnea Diseases 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 12
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 208000020016 psychiatric disease Diseases 0.000 claims description 11
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000006333 difluoro benzoyl group Chemical group 0.000 claims description 10
- 208000020685 sleep-wake disease Diseases 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 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 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 7
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 7
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 6
- IFPYUMUOSRWJPM-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-piperidin-4-ylbenzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCNCC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F IFPYUMUOSRWJPM-UHFFFAOYSA-N 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- UVNXSNUUONIEKA-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2C=NNC2=CC=1)F)CCCN1CCCC1 UVNXSNUUONIEKA-UHFFFAOYSA-N 0.000 claims description 5
- HSKVFCUSNYYKBX-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2C=CNC2=CC=1)F)CCN1CCCC1 HSKVFCUSNYYKBX-UHFFFAOYSA-N 0.000 claims description 5
- IKFVERNEDYZIRR-UHFFFAOYSA-N 6-[5-[[(4-fluorophenyl)methyl-(1-methylpiperidin-4-yl)amino]methyl]furan-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1N(CC=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CO1 IKFVERNEDYZIRR-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
- DPKOENODKZISQV-UHFFFAOYSA-N n'-[[3-(2h-benzotriazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylpropane-1,3-diamine Chemical compound C=1C=CC(C=2C=C3N=NNC3=CC=2)=CC=1CN(CCCN(C)C)CC1=CC=CC=C1 DPKOENODKZISQV-UHFFFAOYSA-N 0.000 claims description 5
- JSCTYNKYJGSRJV-UHFFFAOYSA-N n'-benzyl-n'-[[3-(1h-indol-5-yl)phenyl]methyl]-n,n-dimethylethane-1,2-diamine Chemical compound C=1C=CC(C=2C=C3C=CNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JSCTYNKYJGSRJV-UHFFFAOYSA-N 0.000 claims description 5
- PLMOMLSRTDHBEA-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2C=CNC2=CC=1)F)CC1=CC=C(F)C=C1 PLMOMLSRTDHBEA-UHFFFAOYSA-N 0.000 claims description 5
- WSPPLTHLDDBMBV-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F WSPPLTHLDDBMBV-UHFFFAOYSA-N 0.000 claims description 5
- KRBDRYLXOICLQH-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(1-propan-2-ylpiperidin-4-yl)benzamide Chemical compound C1CN(C(C)C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F KRBDRYLXOICLQH-UHFFFAOYSA-N 0.000 claims description 5
- ZKLWBLVHYUYTIU-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-(1-cyclopropylpiperidin-4-yl)-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCN(CC1)C1CC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F ZKLWBLVHYUYTIU-UHFFFAOYSA-N 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- RGSJEKWEARVCBT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-pyrrolo[2,3-c]pyridin-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1N=CC=2NC=CC=2C=1)F)CCN1CCCC1 RGSJEKWEARVCBT-UHFFFAOYSA-N 0.000 claims description 4
- MQHOLIFSZFIBGH-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-n-[[4-(1h-indazol-5-yl)furan-2-yl]methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CO1 MQHOLIFSZFIBGH-UHFFFAOYSA-N 0.000 claims description 4
- ZOMCDVCZLMXNCC-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide Chemical class C=1C(C=2C=C3OC(=O)NC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 ZOMCDVCZLMXNCC-UHFFFAOYSA-N 0.000 claims description 4
- NIPWIQYSANKKFM-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1N=CC(C=2C=C3C=CNC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 NIPWIQYSANKKFM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- YFQFIPQQCGDESN-UHFFFAOYSA-N 4-chloro-n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(Cl)C=C1 YFQFIPQQCGDESN-UHFFFAOYSA-N 0.000 claims description 3
- DFSFDJWPILSHHC-UHFFFAOYSA-N 4-chloro-n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(Cl)C=C1 DFSFDJWPILSHHC-UHFFFAOYSA-N 0.000 claims description 3
- HTCWMWGQTZLIIX-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-3-yl)benzamide Chemical compound C1N(C)CCCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F HTCWMWGQTZLIIX-UHFFFAOYSA-N 0.000 claims description 3
- BHRCOVLBWBPNGM-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F BHRCOVLBWBPNGM-UHFFFAOYSA-N 0.000 claims description 3
- ZTIJZNIXULPFNV-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2C=NNC2=CC=1)F)CCN1CCCC1 ZTIJZNIXULPFNV-UHFFFAOYSA-N 0.000 claims description 3
- YARYXWNULHXGCT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F YARYXWNULHXGCT-UHFFFAOYSA-N 0.000 claims description 3
- UWLSAXUNLOGZKG-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-pyrrolo[3,2-b]pyridin-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1N=C2C=CNC2=CC=1)F)CCN1CCCC1 UWLSAXUNLOGZKG-UHFFFAOYSA-N 0.000 claims description 3
- MMLOGCJLVYBGMT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=C1F MMLOGCJLVYBGMT-UHFFFAOYSA-N 0.000 claims description 3
- VXJWXSCPMIQSMI-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2OC(=O)NC2=CC=1)F)CCN1CCCC1 VXJWXSCPMIQSMI-UHFFFAOYSA-N 0.000 claims description 3
- XJNQGSDHNHZIJS-UHFFFAOYSA-N 4-fluoro-n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 XJNQGSDHNHZIJS-UHFFFAOYSA-N 0.000 claims description 3
- NASREVVWFJQBIN-UHFFFAOYSA-N 4-fluoro-n-[[3-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C=C(F)C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 NASREVVWFJQBIN-UHFFFAOYSA-N 0.000 claims description 3
- YEGQCJSXNDCXJQ-UHFFFAOYSA-N 4-fluoro-n-[[4-(1h-indazol-5-yl)furan-2-yl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CO1 YEGQCJSXNDCXJQ-UHFFFAOYSA-N 0.000 claims description 3
- FRHCJJWSMXDBKW-UHFFFAOYSA-N 4-fluoro-n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CO1 FRHCJJWSMXDBKW-UHFFFAOYSA-N 0.000 claims description 3
- TXPJMHQDCBOKKE-UHFFFAOYSA-N 4-fluoro-n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC=C(F)C(C=2C=C3C=CNC3=CC=2)=C1 TXPJMHQDCBOKKE-UHFFFAOYSA-N 0.000 claims description 3
- VRWQGLFKUQTKQC-UHFFFAOYSA-N 4-fluoro-n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C(F)=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 VRWQGLFKUQTKQC-UHFFFAOYSA-N 0.000 claims description 3
- XTAMTJXBUKKGSM-UHFFFAOYSA-N 4-fluoro-n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C=NC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 XTAMTJXBUKKGSM-UHFFFAOYSA-N 0.000 claims description 3
- YYNCJJLOAKQESC-UHFFFAOYSA-N 4-fluoro-n-[[5-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1SC(=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 YYNCJJLOAKQESC-UHFFFAOYSA-N 0.000 claims description 3
- PNEOKAGWIFEWNK-UHFFFAOYSA-N 5-[3-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-1h-indole Chemical compound C1CN(C)CCCN1CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 PNEOKAGWIFEWNK-UHFFFAOYSA-N 0.000 claims description 3
- IIZXKGJRAXFWTJ-UHFFFAOYSA-N 5-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 IIZXKGJRAXFWTJ-UHFFFAOYSA-N 0.000 claims description 3
- HAAPQNSHWVROTN-UHFFFAOYSA-N 5-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-2h-benzotriazole Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3N=NNC3=CC=2)=C1 HAAPQNSHWVROTN-UHFFFAOYSA-N 0.000 claims description 3
- UIHVZHGNGWCBFR-UHFFFAOYSA-N 5-[3-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]-4-fluorophenyl]-1h-indole-3-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C(C=2C=C3C(C#N)=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)CC1=CC=C(F)C=C1 UIHVZHGNGWCBFR-UHFFFAOYSA-N 0.000 claims description 3
- CAKWHMWWQGQGJS-UHFFFAOYSA-N 5-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-1,3-dihydrobenzimidazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3NC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CAKWHMWWQGQGJS-UHFFFAOYSA-N 0.000 claims description 3
- POCWULSIEIASHP-UHFFFAOYSA-N 5-[4-fluoro-3-[(2-thiophen-2-ylpiperazin-1-yl)methyl]phenyl]-1h-indazole Chemical compound FC1=CC=C(C=2C=C3C=NNC3=CC=2)C=C1CN1CCNCC1C1=CC=CS1 POCWULSIEIASHP-UHFFFAOYSA-N 0.000 claims description 3
- CBGLMQWHEAXZDJ-UHFFFAOYSA-N 5-[4-fluoro-3-[(4-methyl-2-pyridin-4-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=NC=C1 CBGLMQWHEAXZDJ-UHFFFAOYSA-N 0.000 claims description 3
- WZNQSOMASICACW-UHFFFAOYSA-N 5-[4-fluoro-3-[(4-methylpiperazin-1-yl)methyl]phenyl]-2h-benzotriazole Chemical compound C1CN(C)CCN1CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F WZNQSOMASICACW-UHFFFAOYSA-N 0.000 claims description 3
- GJHBOZUUYVMRNH-UHFFFAOYSA-N 5-[4-fluoro-3-[[2-(4-fluorophenyl)piperazin-1-yl]methyl]phenyl]-1h-indazole Chemical compound C1=CC(F)=CC=C1C1N(CC=2C(=CC=C(C=2)C=2C=C3C=NNC3=CC=2)F)CCNC1 GJHBOZUUYVMRNH-UHFFFAOYSA-N 0.000 claims description 3
- MNGZJBFTHGLPQE-UHFFFAOYSA-N 5-[4-fluoro-3-[[2-(furan-2-yl)-4-methylpiperazin-1-yl]methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CO1 MNGZJBFTHGLPQE-UHFFFAOYSA-N 0.000 claims description 3
- GQFXAFQSILNKAW-UHFFFAOYSA-N 5-[4-fluoro-3-[[4-methyl-2-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=C(C(F)(F)F)C=C1 GQFXAFQSILNKAW-UHFFFAOYSA-N 0.000 claims description 3
- REPHVNGRWIFVMJ-UHFFFAOYSA-N 6-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3OC(=O)NC3=CC=2)=C1 REPHVNGRWIFVMJ-UHFFFAOYSA-N 0.000 claims description 3
- JLMVYNXQXVHUDX-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3h-1,3-benzothiazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JLMVYNXQXVHUDX-UHFFFAOYSA-N 0.000 claims description 3
- JJPMWPVVCZNYSC-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3h-1,3-benzoxazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JJPMWPVVCZNYSC-UHFFFAOYSA-N 0.000 claims description 3
- BYNVFXLKWAWEFK-UHFFFAOYSA-N 6-[4-fluoro-3-[(2-thiophen-2-ylpiperazin-1-yl)methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound FC1=CC=C(C=2C=C3OC(=O)NC3=CC=2)C=C1CN1CCNCC1C1=CC=CS1 BYNVFXLKWAWEFK-UHFFFAOYSA-N 0.000 claims description 3
- FTLJTVKXADVTQC-UHFFFAOYSA-N 6-[4-fluoro-3-[[(4-fluorophenyl)methyl-(1-methylpiperidin-4-yl)amino]methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2OC(=O)NC2=CC=1)F)CC1=CC=C(F)C=C1 FTLJTVKXADVTQC-UHFFFAOYSA-N 0.000 claims description 3
- DXBFXQJNQZFORV-UHFFFAOYSA-N 6-[5-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]furan-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C=1C(C=2C=C3OC(=O)NC3=CC=2)=COC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 DXBFXQJNQZFORV-UHFFFAOYSA-N 0.000 claims description 3
- HBINRFRIDMACKS-UHFFFAOYSA-N 6-[5-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]pyridin-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C=1N=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 HBINRFRIDMACKS-UHFFFAOYSA-N 0.000 claims description 3
- NZGZNNPUIKUMJG-UHFFFAOYSA-N N-[[5-(2H-benzotriazol-5-yl)-2-fluorophenyl]methyl]-N-(2-pyrrolidin-1-ylethyl)thiophene-2-carboxamide hydrochloride Chemical compound Cl.FC1=CC=C(C=2C=C3N=NNC3=CC=2)C=C1CN(C(=O)C=1SC=CC=1)CCN1CCCC1 NZGZNNPUIKUMJG-UHFFFAOYSA-N 0.000 claims description 3
- AMQQXFJTGQJTCT-UHFFFAOYSA-N acetic acid;4-fluoro-n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound CC(O)=O.C1=CC(F)=CC=C1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 AMQQXFJTGQJTCT-UHFFFAOYSA-N 0.000 claims description 3
- OMNCZRGZYURYEO-UHFFFAOYSA-N acetic acid;5-[4-fluoro-3-[(2-thiophen-2-ylpiperazin-1-yl)methyl]phenyl]-1h-indazole Chemical compound CC(O)=O.FC1=CC=C(C=2C=C3C=NNC3=CC=2)C=C1CN1CCNCC1C1=CC=CS1 OMNCZRGZYURYEO-UHFFFAOYSA-N 0.000 claims description 3
- SJFFDJGHUDCLNC-UHFFFAOYSA-N acetic acid;5-[4-fluoro-3-[(4-methyl-2-pyridin-2-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound CC(O)=O.C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CC=N1 SJFFDJGHUDCLNC-UHFFFAOYSA-N 0.000 claims description 3
- ZATHGVHUMFFOPY-UHFFFAOYSA-N acetic acid;5-[4-fluoro-3-[(4-methyl-2-pyridin-3-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound CC(O)=O.C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CN=C1 ZATHGVHUMFFOPY-UHFFFAOYSA-N 0.000 claims description 3
- WHSAOBZVNVTBQH-UHFFFAOYSA-N acetic acid;n'-[(4-fluorophenyl)methyl]-n'-[[5-(1h-indazol-5-yl)pyridin-3-yl]methyl]-n,n-dimethylethane-1,2-diamine Chemical compound CC(O)=O.C=1N=CC(C=2C=C3C=NNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 WHSAOBZVNVTBQH-UHFFFAOYSA-N 0.000 claims description 3
- AJXIDXPJRCDQNV-UHFFFAOYSA-N acetic acid;n-(1-azabicyclo[2.2.2]octan-4-ylmethyl)-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-1-(4-fluorophenyl)methanamine Chemical class CC(O)=O.C1=CC(F)=CC=C1CN(CC12CCN(CC1)CC2)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F AJXIDXPJRCDQNV-UHFFFAOYSA-N 0.000 claims description 3
- NNEUDDYXKARJJP-UHFFFAOYSA-N acetic acid;n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethoxy)benzamide Chemical compound CC(O)=O.C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CC(OC(F)(F)F)=CC=1)CCN1CCCC1 NNEUDDYXKARJJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 3
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
- NORFKNIONUICLG-UHFFFAOYSA-N n'-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n'-[(4-fluorophenyl)methyl]-n-methylethane-1,2-diamine Chemical compound C=1C(C=2C=C3C=NNC3=CC=2)=CC=C(F)C=1CN(CCNC)CC1=CC=C(F)C=C1 NORFKNIONUICLG-UHFFFAOYSA-N 0.000 claims description 3
- VJPMQXAWZUFURF-UHFFFAOYSA-N n'-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n'-[(4-fluorophenyl)methyl]-n,n-dimethylethane-1,2-diamine Chemical compound C=1C(C=2C=C3C=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)CC1=CC=C(F)C=C1 VJPMQXAWZUFURF-UHFFFAOYSA-N 0.000 claims description 3
- XTKIJZIFRJNQDD-UHFFFAOYSA-N n'-[[3-(2h-benzotriazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylethane-1,2-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3N=NNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 XTKIJZIFRJNQDD-UHFFFAOYSA-N 0.000 claims description 3
- VPEYZBPHUGTNEJ-UHFFFAOYSA-N n'-[[3-(3h-benzimidazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylethane-1,2-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3N=CNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 VPEYZBPHUGTNEJ-UHFFFAOYSA-N 0.000 claims description 3
- NAYKHKCDIGPIHB-UHFFFAOYSA-N n'-[[3-(3h-benzimidazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylpropane-1,3-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3N=CNC3=CC=2)=CC=1CN(CCCN(C)C)CC1=CC=CC=C1 NAYKHKCDIGPIHB-UHFFFAOYSA-N 0.000 claims description 3
- RBHFMNPEVIQOAQ-UHFFFAOYSA-N n'-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n'-[(4-fluorophenyl)methyl]-n-methylethane-1,2-diamine Chemical compound C=1C(C=2C=C3N=NNC3=CC=2)=CC=C(F)C=1CN(CCNC)CC1=CC=C(F)C=C1 RBHFMNPEVIQOAQ-UHFFFAOYSA-N 0.000 claims description 3
- CLRXDNKIZRKYCU-UHFFFAOYSA-N n'-benzyl-n'-[[3-(1h-indazol-5-yl)phenyl]methyl]-n,n-dimethylethane-1,2-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3C=NNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CLRXDNKIZRKYCU-UHFFFAOYSA-N 0.000 claims description 3
- MFQZPMOHMWBCSP-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-4-ylmethyl)-4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(F)=CC=C1C(=O)N(CC12CCN(CC1)CC2)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F MFQZPMOHMWBCSP-UHFFFAOYSA-N 0.000 claims description 3
- BPOOZSRHPOZVSF-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide Chemical compound CCN1CCCC1CN(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=C1F BPOOZSRHPOZVSF-UHFFFAOYSA-N 0.000 claims description 3
- JYWGKSVZWUYLJD-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]benzamide Chemical compound C=1C(C=2C=C3C=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 JYWGKSVZWUYLJD-UHFFFAOYSA-N 0.000 claims description 3
- NKFKIKMCCXYSCY-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(2-methyl-1h-indol-5-yl)phenyl]methyl]benzamide Chemical compound C=1C(C=2C=C3C=C(C)NC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 NKFKIKMCCXYSCY-UHFFFAOYSA-N 0.000 claims description 3
- NSJJGGIMSVSOJR-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]thiophene-2-carboxamide Chemical compound C=1C(C=2C=C3C=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=CS1 NSJJGGIMSVSOJR-UHFFFAOYSA-N 0.000 claims description 3
- NKYLVIKUMDSXAE-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=CC=C1 NKYLVIKUMDSXAE-UHFFFAOYSA-N 0.000 claims description 3
- KUXBBRSOZSVBLV-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=CC=C1 KUXBBRSOZSVBLV-UHFFFAOYSA-N 0.000 claims description 3
- UAVIRLMJQFOHCI-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCCN(C)C)C(=O)C1=CC=CC=C1 UAVIRLMJQFOHCI-UHFFFAOYSA-N 0.000 claims description 3
- SHHRTUXBEDCURH-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2C=NNC2=CC=1)F)CC1=CC=C(F)C=C1 SHHRTUXBEDCURH-UHFFFAOYSA-N 0.000 claims description 3
- WRTMCHZDWZBKEX-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1CN(C1CCNCC1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F WRTMCHZDWZBKEX-UHFFFAOYSA-N 0.000 claims description 3
- HPXVEQFJLMKKQR-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-1,3-benzodioxole-5-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=C2OCOC2=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F HPXVEQFJLMKKQR-UHFFFAOYSA-N 0.000 claims description 3
- VFBKHCBRWHKPMN-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-2,3-dihydro-1,4-benzodioxine-6-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=C2OCCOC2=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F VFBKHCBRWHKPMN-UHFFFAOYSA-N 0.000 claims description 3
- OVVKQDMOZMPOLX-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=C(OC(F)(F)F)C=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F OVVKQDMOZMPOLX-UHFFFAOYSA-N 0.000 claims description 3
- CCYBEFNZYMOGBN-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-3-propan-2-yloxybenzamide Chemical compound CC(C)OC1=CC=CC(C(=O)N(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C2CCN(C)CC2)=C1 CCYBEFNZYMOGBN-UHFFFAOYSA-N 0.000 claims description 3
- LLLHDFLJXAIDBE-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F LLLHDFLJXAIDBE-UHFFFAOYSA-N 0.000 claims description 3
- IKCFVRJQWIBCNY-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-propan-2-yloxybenzamide Chemical compound C1=CC(OC(C)C)=CC=C1C(=O)N(C1CCN(C)CC1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F IKCFVRJQWIBCNY-UHFFFAOYSA-N 0.000 claims description 3
- PKFQTSKCDVPHJQ-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrazine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=NC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F PKFQTSKCDVPHJQ-UHFFFAOYSA-N 0.000 claims description 3
- AHDUMCHMYSFHIU-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridazine-3-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=NC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F AHDUMCHMYSFHIU-UHFFFAOYSA-N 0.000 claims description 3
- SPAYHXLHIKDLME-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridazine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=NN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F SPAYHXLHIKDLME-UHFFFAOYSA-N 0.000 claims description 3
- CDOHEHXGAQIAPA-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F CDOHEHXGAQIAPA-UHFFFAOYSA-N 0.000 claims description 3
- XYISUNRTGJYVAR-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-3-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=NC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F XYISUNRTGJYVAR-UHFFFAOYSA-N 0.000 claims description 3
- DPFXEHRVNPYVOK-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F DPFXEHRVNPYVOK-UHFFFAOYSA-N 0.000 claims description 3
- IVNGUWJYSQCFEP-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrimidine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=CN=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F IVNGUWJYSQCFEP-UHFFFAOYSA-N 0.000 claims description 3
- PHWDKOGPGBMXBK-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrimidine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F PHWDKOGPGBMXBK-UHFFFAOYSA-N 0.000 claims description 3
- YPMFOVMXSKGTSS-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)thiophene-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1SC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F YPMFOVMXSKGTSS-UHFFFAOYSA-N 0.000 claims description 3
- DLFONWAJSZOKII-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound FC1=CC=C(C=2C=C3C=CNC3=CC=2)C=C1CN(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CCN1CCCC1 DLFONWAJSZOKII-UHFFFAOYSA-N 0.000 claims description 3
- GHKZCYUPGIOECR-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound FC1=CC=C(C=2C=C3C=CNC3=CC=2)C=C1CN(C(=O)C=1C=CN=CC=1)CCN1CCCC1 GHKZCYUPGIOECR-UHFFFAOYSA-N 0.000 claims description 3
- XMKVXVQEBWOGDB-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 XMKVXVQEBWOGDB-UHFFFAOYSA-N 0.000 claims description 3
- UHRYIQCHOOCYHR-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CN=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 UHRYIQCHOOCYHR-UHFFFAOYSA-N 0.000 claims description 3
- JEPATVHORFCQTI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)thiophene-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1SC=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 JEPATVHORFCQTI-UHFFFAOYSA-N 0.000 claims description 3
- BUPSNLWDMCEPMU-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 BUPSNLWDMCEPMU-UHFFFAOYSA-N 0.000 claims description 3
- WOGYNPXAPRCMRZ-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 WOGYNPXAPRCMRZ-UHFFFAOYSA-N 0.000 claims description 3
- WXHGDNBVTXGJQI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 WXHGDNBVTXGJQI-UHFFFAOYSA-N 0.000 claims description 3
- HEIAVMHOQKGYKI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 HEIAVMHOQKGYKI-UHFFFAOYSA-N 0.000 claims description 3
- DYFGGUFRZROJMX-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 DYFGGUFRZROJMX-UHFFFAOYSA-N 0.000 claims description 3
- PAPQFLQECSCDRM-UHFFFAOYSA-N n-[[3-(2h-benzotriazol-5-yl)phenyl]methyl]-4-fluoro-n-(2-pyrrolidin-1-ylethyl)benzamide;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2N=NNC2=CC=1)CCN1CCCC1 PAPQFLQECSCDRM-UHFFFAOYSA-N 0.000 claims description 3
- CWLGPJRYTWNWLZ-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 CWLGPJRYTWNWLZ-UHFFFAOYSA-N 0.000 claims description 3
- WIQSUHUOXHJYDP-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 WIQSUHUOXHJYDP-UHFFFAOYSA-N 0.000 claims description 3
- MYFMPMMPCJUFDW-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 MYFMPMMPCJUFDW-UHFFFAOYSA-N 0.000 claims description 3
- OVCJQDAKFFGOCX-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 OVCJQDAKFFGOCX-UHFFFAOYSA-N 0.000 claims description 3
- CWVWGQFRGMHKAB-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 CWVWGQFRGMHKAB-UHFFFAOYSA-N 0.000 claims description 3
- QQRSLCPFFHYMTJ-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 QQRSLCPFFHYMTJ-UHFFFAOYSA-N 0.000 claims description 3
- AUZVTFKQFHYBDX-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 AUZVTFKQFHYBDX-UHFFFAOYSA-N 0.000 claims description 3
- KPVUJWOELRRDSC-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 KPVUJWOELRRDSC-UHFFFAOYSA-N 0.000 claims description 3
- PIYMZBQSRQXRDX-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 PIYMZBQSRQXRDX-UHFFFAOYSA-N 0.000 claims description 3
- YZCCXNKYEHALHU-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 YZCCXNKYEHALHU-UHFFFAOYSA-N 0.000 claims description 3
- JLLLXEFQWHSKHC-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 JLLLXEFQWHSKHC-UHFFFAOYSA-N 0.000 claims description 3
- QFSMXEBVMOQSNT-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 QFSMXEBVMOQSNT-UHFFFAOYSA-N 0.000 claims description 3
- PCFIHKBUEKEQGD-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CCN1CCCC1 PCFIHKBUEKEQGD-UHFFFAOYSA-N 0.000 claims description 3
- PARQLKCEFTVVPF-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CN=CC=1)CCN1CCCC1 PARQLKCEFTVVPF-UHFFFAOYSA-N 0.000 claims description 3
- OTDQLXGENODYNT-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1N=CC=CC=1)CCCN1CCCC1 OTDQLXGENODYNT-UHFFFAOYSA-N 0.000 claims description 3
- UDFOJJRJSZPOPQ-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CN=CC=1)CCCN1CCCC1 UDFOJJRJSZPOPQ-UHFFFAOYSA-N 0.000 claims description 3
- ALGRRZXZWPBSSM-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-2,4-difluoro-n-(2-pyrrolidin-1-ylethyl)benzamide;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CCN1CCCC1 ALGRRZXZWPBSSM-UHFFFAOYSA-N 0.000 claims description 3
- YDVLMPIGLAODFV-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CCN1CCCC1 YDVLMPIGLAODFV-UHFFFAOYSA-N 0.000 claims description 3
- SFIIUXLAGNDLGX-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-(thiophen-2-ylmethyl)piperidin-4-amine Chemical compound FC1=CC=C(C=2C=C3N=NNC3=CC=2)C=C1CN(C1CCNCC1)CC1=CC=CS1 SFIIUXLAGNDLGX-UHFFFAOYSA-N 0.000 claims description 3
- RXJNOKWXAVVCGR-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine;hydrochloride Chemical compound Cl.C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CC1=CC=C(F)C=C1 RXJNOKWXAVVCGR-UHFFFAOYSA-N 0.000 claims description 3
- MWBKYWAJVNXSPQ-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1CN(C1CCNCC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F MWBKYWAJVNXSPQ-UHFFFAOYSA-N 0.000 claims description 3
- ZSZBDOJQRFGYBF-UHFFFAOYSA-N n-[[5-(3-cyano-1h-indol-5-yl)-2-fluorophenyl]methyl]-n-[2-(dimethylamino)ethyl]-4-fluorobenzamide Chemical compound C=1C(C=2C=C3C(C#N)=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 ZSZBDOJQRFGYBF-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- ITEOLDGOKAKQIM-UHFFFAOYSA-N 4-chloro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(Cl)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F ITEOLDGOKAKQIM-UHFFFAOYSA-N 0.000 claims description 2
- CLAHVIWPABLYNF-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3-methyl-1h-quinazoline-2,4-dione;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3C(=O)N(C)C(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CLAHVIWPABLYNF-UHFFFAOYSA-N 0.000 claims description 2
- BMKNTDUWMJGKRI-UHFFFAOYSA-N 7-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one Chemical class C=1C=CC(C=2C=C3OCC(=O)NC3=NC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 BMKNTDUWMJGKRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- UJJWRSYPYQWWFJ-UHFFFAOYSA-N n-[[2-chloro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1Cl UJJWRSYPYQWWFJ-UHFFFAOYSA-N 0.000 claims description 2
- BPIPIBXGOHQVAI-UHFFFAOYSA-N n-[[5-(2,3-dihydro-1h-indol-5-yl)-2-fluorophenyl]methyl]-n-[2-(dimethylamino)ethyl]-4-fluorobenzamide Chemical compound C=1C(C=2C=C3CCNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 BPIPIBXGOHQVAI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims 1
- MHRWDIMYIWMUOS-UHFFFAOYSA-N 7-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OCC(=O)NC3=NC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 MHRWDIMYIWMUOS-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 41
- 238000011282 treatment Methods 0.000 abstract description 26
- 201000010099 disease Diseases 0.000 abstract description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 332
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 239000000047 product Substances 0.000 description 80
- 239000000243 solution Substances 0.000 description 80
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 70
- 238000004587 chromatography analysis Methods 0.000 description 48
- 230000014759 maintenance of location Effects 0.000 description 46
- 235000019439 ethyl acetate Nutrition 0.000 description 45
- 239000012043 crude product Substances 0.000 description 44
- 230000007958 sleep Effects 0.000 description 42
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000012267 brine Substances 0.000 description 37
- 239000012074 organic phase Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 35
- 235000019341 magnesium sulphate Nutrition 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000008346 aqueous phase Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- 239000003039 volatile agent Substances 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 229960000583 acetic acid Drugs 0.000 description 26
- 238000012360 testing method Methods 0.000 description 25
- 208000035475 disorder Diseases 0.000 description 24
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 24
- 239000007858 starting material Substances 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 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 20
- 230000000694 effects Effects 0.000 description 20
- 238000005259 measurement Methods 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 229940079593 drug Drugs 0.000 description 17
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 16
- 101150003085 Pdcl gene Proteins 0.000 description 15
- 229910000029 sodium carbonate Inorganic materials 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 12
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 11
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- 230000037322 slow-wave sleep Effects 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000007983 Tris buffer Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 10
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 230000000241 respiratory effect Effects 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 239000007821 HATU Substances 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 230000037053 non-rapid eye movement Effects 0.000 description 8
- 229940076279 serotonin Drugs 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 235000019256 formaldehyde Nutrition 0.000 description 6
- 229960004279 formaldehyde Drugs 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 201000002859 sleep apnea Diseases 0.000 description 6
- 229960000278 theophylline Drugs 0.000 description 6
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000004480 active ingredient Substances 0.000 description 5
- 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 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- 238000002567 electromyography Methods 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 230000001766 physiological effect Effects 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000005932 reductive alkylation reaction Methods 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
- 229960004799 tryptophan Drugs 0.000 description 5
- VHADYSUJZAPXOW-UHFFFAOYSA-N 1h-indol-5-ylboronic acid Chemical compound OB(O)C1=CC=C2NC=CC2=C1 VHADYSUJZAPXOW-UHFFFAOYSA-N 0.000 description 4
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 101150003479 Parg gene Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 206010041349 Somnolence Diseases 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 208000008784 apnea Diseases 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- 239000007822 coupling agent Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 230000000414 obstructive effect Effects 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000033764 rhythmic process Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 230000003860 sleep quality Effects 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 3
- MIANLSMIRRRMJS-UHFFFAOYSA-N 5-meo-dmt Chemical compound [CH]1C(OC)=CC=C2N=CC(CCN(C)C)=C21 MIANLSMIRRRMJS-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 3
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 230000037007 arousal Effects 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- BBIOIIDDANTAIE-UHFFFAOYSA-N ethyl 6-chloropyrazine-2-carboxylate Chemical compound CCOC(=O)C1=CN=CC(Cl)=N1 BBIOIIDDANTAIE-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 206010020765 hypersomnia Diseases 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 208000024714 major depressive disease Diseases 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 201000003631 narcolepsy Diseases 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000002831 pharmacologic agent Substances 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000008667 sleep stage Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UBAZQJTUNPKEGK-UHFFFAOYSA-N tert-butyl 5-(4-fluoro-3-formylphenyl)indazole-1-carboxylate Chemical compound C=1C=C2N(C(=O)OC(C)(C)C)N=CC2=CC=1C1=CC=C(F)C(C=O)=C1 UBAZQJTUNPKEGK-UHFFFAOYSA-N 0.000 description 3
- LHUTYYZPRLPJBP-QGZVFWFLSA-N (2s)-1-[(5-bromopyridin-3-yl)methyl]-2-(4-fluorophenyl)-4-methylpiperazine Chemical compound C([C@@H]1C=2C=CC(F)=CC=2)N(C)CCN1CC1=CN=CC(Br)=C1 LHUTYYZPRLPJBP-QGZVFWFLSA-N 0.000 description 2
- ACBRRQXDTXAEOY-MRXNPFEDSA-N (2s)-1-[(5-bromopyridin-3-yl)methyl]-2-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1[C@@H]1N(CC=2C=C(Br)C=NC=2)CCNC1 ACBRRQXDTXAEOY-MRXNPFEDSA-N 0.000 description 2
- ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- JCLNUEKQAMBXMA-UHFFFAOYSA-N 2-fluoro-5-(1h-indol-5-yl)benzaldehyde Chemical compound C1=C(C=O)C(F)=CC=C1C1=CC=C(NC=C2)C2=C1 JCLNUEKQAMBXMA-UHFFFAOYSA-N 0.000 description 2
- KKJQPUXQUQWGRA-UHFFFAOYSA-N 2-trimethylsilylethyl 4-aminopiperidine-1-carboxylate Chemical compound C[Si](C)(C)CCOC(=O)N1CCC(N)CC1 KKJQPUXQUQWGRA-UHFFFAOYSA-N 0.000 description 2
- QKEKUZYEHOVYSN-UHFFFAOYSA-N 3-(1h-indol-5-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 QKEKUZYEHOVYSN-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- PPKHNELPQYJFOF-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]-n-piperidin-4-ylbenzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCNCC1)CC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F PPKHNELPQYJFOF-UHFFFAOYSA-N 0.000 description 2
- DAEFYSALPBXCIY-UHFFFAOYSA-N 5-(1h-indol-5-yl)pyridine-3-carbaldehyde Chemical compound O=CC1=CN=CC(C=2C=C3C=CNC3=CC=2)=C1 DAEFYSALPBXCIY-UHFFFAOYSA-N 0.000 description 2
- NGUVGKAEOFPLDT-UHFFFAOYSA-N 5-bromopyridine-3-carbaldehyde Chemical compound BrC1=CN=CC(C=O)=C1 NGUVGKAEOFPLDT-UHFFFAOYSA-N 0.000 description 2
- MIYODQRDAPJMKK-UHFFFAOYSA-N 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-trityl-1,3-benzoxazol-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N(C(=O)O2)C(C=3C=CC=CC=3)(C=3C=CC=CC=3)C=3C=CC=CC=3)C2=C1 MIYODQRDAPJMKK-UHFFFAOYSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 229920001774 Perfluoroether Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 206010041235 Snoring Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- CCXCSQNTXCXIIW-UHFFFAOYSA-N [6-(1h-indol-5-yl)pyrazin-2-yl]methanol Chemical compound OCC1=CN=CC(C=2C=C3C=CNC3=CC=2)=N1 CCXCSQNTXCXIIW-UHFFFAOYSA-N 0.000 description 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 2
- 239000003420 antiserotonin agent Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- KKAXNAVSOBXHTE-UHFFFAOYSA-N boranamine Chemical compound NB KKAXNAVSOBXHTE-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- DDNKJFBQMQOIKI-UHFFFAOYSA-N cincreasin Chemical compound BrC1=CC=C2NC(=O)OC2=C1 DDNKJFBQMQOIKI-UHFFFAOYSA-N 0.000 description 2
- 238000010549 co-Evaporation Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 239000012055 enteric layer Substances 0.000 description 2
- AHNYWCSSTXQJAT-UHFFFAOYSA-N ethyl 6-(1h-indol-5-yl)pyrazine-2-carboxylate Chemical compound CCOC(=O)C1=CN=CC(C=2C=C3C=CNC3=CC=2)=N1 AHNYWCSSTXQJAT-UHFFFAOYSA-N 0.000 description 2
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000013022 formulation composition Substances 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 239000003326 hypnotic agent Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000003434 inspiratory effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 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
- 238000004949 mass spectrometry Methods 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- HPIUNUJXFFFCJC-UHFFFAOYSA-N n'-benzyl-n,n-dimethyl-n'-[[3-(1-tritylbenzotriazol-5-yl)phenyl]methyl]propane-1,3-diamine Chemical compound C=1C=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=1CN(CCCN(C)C)CC1=CC=CC=C1 HPIUNUJXFFFCJC-UHFFFAOYSA-N 0.000 description 2
- KTNIQNANOUEQKT-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1NCC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F KTNIQNANOUEQKT-UHFFFAOYSA-N 0.000 description 2
- LLSJAFHDYCTFCM-UHFFFAOYSA-N n-benzyl-n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCNCC1=CC=CC=C1 LLSJAFHDYCTFCM-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 150000002941 palladium compounds Chemical class 0.000 description 2
- 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 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000004461 rapid eye movement Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- MMXDKXUKSKMROG-UHFFFAOYSA-N tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole-1-carboxylate Chemical compound C=1C=C2N(C(=O)OC(C)(C)C)N=CC2=CC=1B1OC(C)(C)C(C)(C)O1 MMXDKXUKSKMROG-UHFFFAOYSA-N 0.000 description 2
- CAQGDWLRIQCXSP-UHFFFAOYSA-N tert-butyl 5-bromoindazole-1-carboxylate Chemical compound BrC1=CC=C2N(C(=O)OC(C)(C)C)N=CC2=C1 CAQGDWLRIQCXSP-UHFFFAOYSA-N 0.000 description 2
- WTCJDYCLDLRHRI-UHFFFAOYSA-N tert-butyl indazole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)N=CC2=C1 WTCJDYCLDLRHRI-UHFFFAOYSA-N 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- BZMMRNKDONDVIB-UHFFFAOYSA-N (1-ethoxycyclopropyl)oxy-trimethylsilane Chemical compound CCOC1(O[Si](C)(C)C)CC1 BZMMRNKDONDVIB-UHFFFAOYSA-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
- IANGWZHSENIUTD-JOCHJYFZSA-N (2s)-2-(4-fluorophenyl)-1-[[2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]-4-methylpiperazine Chemical compound C([C@@H]1C=2C=CC(F)=CC=2)N(C)CCN1CC(C(=CC=1)F)=CC=1B1OC(C)(C)C(C)(C)O1 IANGWZHSENIUTD-JOCHJYFZSA-N 0.000 description 1
- HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 1
- VWXSREOLBJWSKY-LLVKDONJSA-N (3s)-3-(4-fluorophenyl)-1-methylpiperazine Chemical compound C1N(C)CCN[C@H]1C1=CC=C(F)C=C1 VWXSREOLBJWSKY-LLVKDONJSA-N 0.000 description 1
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 1
- ZAQWGGKIMQIVGM-UHFFFAOYSA-N (4-nitrophenyl) 2-trimethylsilylethyl carbonate Chemical compound C[Si](C)(C)CCOC(=O)OC1=CC=C([N+]([O-])=O)C=C1 ZAQWGGKIMQIVGM-UHFFFAOYSA-N 0.000 description 1
- DBYDGXMEYIIMHC-QGZVFWFLSA-N (5-bromo-2-fluorophenyl)-[(2s)-2-(4-fluorophenyl)-4-methylpiperazin-1-yl]methanone Chemical compound C1([C@@H]2N(CCN(C2)C)C(=O)C=2C(=CC=C(Br)C=2)F)=CC=C(F)C=C1 DBYDGXMEYIIMHC-QGZVFWFLSA-N 0.000 description 1
- MLIVQBJMCNVRGP-MRXNPFEDSA-N (5-bromo-2-fluorophenyl)-[(2s)-2-(4-fluorophenyl)piperazin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1[C@@H]1N(C(=O)C=2C(=CC=C(Br)C=2)F)CCNC1 MLIVQBJMCNVRGP-MRXNPFEDSA-N 0.000 description 1
- HAKRSIFCTAKBRD-TYFJVFSVSA-N (8s,9s,10r,13s,14s,17s)-17-acetyl-1-methoxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1C[C@@H]2[C@@]3(C)C(OC)CC(=O)C=C3CC[C@H]2[C@@H]2CC[C@H](C(C)=O)[C@]21C HAKRSIFCTAKBRD-TYFJVFSVSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- DDHUNHGZUHZNKB-UHFFFAOYSA-N 2,2-dimethylpropane-1,3-diamine Chemical compound NCC(C)(C)CN DDHUNHGZUHZNKB-UHFFFAOYSA-N 0.000 description 1
- WKEJJJKIODATRV-UHFFFAOYSA-N 2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)benzaldehyde Chemical compound C1=C(C=O)C(F)=CC=C1C1=CC=C(NC(=O)O2)C2=C1 WKEJJJKIODATRV-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- FMIPLBRBLOPRFW-UHFFFAOYSA-N 2-piperidin-4-ylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1CCNCC1 FMIPLBRBLOPRFW-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- RKMQSRLHKQNHHH-UHFFFAOYSA-N 2-trimethylsilylethyl 4-[(4-fluorobenzoyl)-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC[Si](C)(C)C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F RKMQSRLHKQNHHH-UHFFFAOYSA-N 0.000 description 1
- UCBXYEKYTITNPO-UHFFFAOYSA-N 2-trimethylsilylethyl 4-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methylamino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC[Si](C)(C)C)CCC1NCC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F UCBXYEKYTITNPO-UHFFFAOYSA-N 0.000 description 1
- UDLGQKCVOJGFGC-UHFFFAOYSA-N 2-trimethylsilylethyl 4-oxopiperidine-1-carboxylate Chemical compound C[Si](C)(C)CCOC(=O)N1CCC(=O)CC1 UDLGQKCVOJGFGC-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MRGBBKQOSUHKPF-UHFFFAOYSA-N 4-bromofuran-2-carbaldehyde Chemical compound BrC1=COC(C=O)=C1 MRGBBKQOSUHKPF-UHFFFAOYSA-N 0.000 description 1
- QVKWZKKLKRZUTQ-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]-n-(1-propan-2-ylpiperidin-4-yl)benzamide Chemical compound C1CN(C(C)C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F QVKWZKKLKRZUTQ-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 1
- CYPMENQZAYYMTF-UHFFFAOYSA-N 5-[4-fluoro-3-[[2-(4-fluorophenyl)-4-methylpiperazin-1-yl]methyl]phenyl]-1h-pyrrolo[3,2-b]pyridine Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2N=C3C=CNC3=CC=2)F)C1C1=CC=C(F)C=C1 CYPMENQZAYYMTF-UHFFFAOYSA-N 0.000 description 1
- STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- MMFGGDVQLQQQRX-UHFFFAOYSA-N 5-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C=C1C=O MMFGGDVQLQQQRX-UHFFFAOYSA-N 0.000 description 1
- PEXAZYDITWXYNJ-UHFFFAOYSA-N 5-bromo-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1F PEXAZYDITWXYNJ-UHFFFAOYSA-N 0.000 description 1
- GDQXDVJFMLNXHX-UHFFFAOYSA-N 5-bromo-3-methyl-1h-indole Chemical compound C1=C(Br)C=C2C(C)=CNC2=C1 GDQXDVJFMLNXHX-UHFFFAOYSA-N 0.000 description 1
- YUSCRYXJQTYGHX-UHFFFAOYSA-N 5-bromoindazole-1-carboxylic acid Chemical compound BrC1=CC=C2N(C(=O)O)N=CC2=C1 YUSCRYXJQTYGHX-UHFFFAOYSA-N 0.000 description 1
- AADCDMQTJNYOSS-LBPRGKRZSA-N 5-chloro-3-ethyl-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2-hydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(CC)=CC(Cl)=C1OC AADCDMQTJNYOSS-LBPRGKRZSA-N 0.000 description 1
- YEFWLDRLVCISIN-UHFFFAOYSA-N 6-[5-[[(1-methylpiperidin-4-yl)amino]methyl]furan-3-yl]-3-trityl-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1NCC1=CC(C=2C=C3OC(=O)N(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CO1 YEFWLDRLVCISIN-UHFFFAOYSA-N 0.000 description 1
- GUSVIXMKBVVXSS-UHFFFAOYSA-N 6-[5-[[(4-fluorophenyl)methyl-(1-methylpiperidin-4-yl)amino]methyl]furan-3-yl]-3-trityl-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1N(CC=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)N(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CO1 GUSVIXMKBVVXSS-UHFFFAOYSA-N 0.000 description 1
- CRKJYSGULUUTIV-UHFFFAOYSA-N 6-bromo-3-trityl-1,3-benzoxazol-2-one Chemical compound O=C1OC2=CC(Br)=CC=C2N1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 CRKJYSGULUUTIV-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
- 239000005541 ACE inhibitor Substances 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COTBDTDTEHXNBT-UHFFFAOYSA-N BC1=CC=CC(C=O)=C1 Chemical compound BC1=CC=CC(C=O)=C1 COTBDTDTEHXNBT-UHFFFAOYSA-N 0.000 description 1
- RKDOZLLIIGBSCY-UHFFFAOYSA-N BC1=CC=CC(CN(CC(C)N(C)C)CC=2C=CC=CC=2)=C1 Chemical compound BC1=CC=CC(CN(CC(C)N(C)C)CC=2C=CC=CC=2)=C1 RKDOZLLIIGBSCY-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000003417 Central Sleep Apnea Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 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
- 229920002307 Dextran Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 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
- 206010013654 Drug abuse Diseases 0.000 description 1
- 206010013980 Dyssomnias Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000979190 Homo sapiens Transcription factor MafB Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 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
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
- 206010027590 Middle insomnia Diseases 0.000 description 1
- DMULVCHRPCFFGV-UHFFFAOYSA-N N,N-dimethyltryptamine Chemical compound C1=CC=C2C(CCN(C)C)=CNC2=C1 DMULVCHRPCFFGV-UHFFFAOYSA-N 0.000 description 1
- WXNXCEHXYPACJF-ZETCQYMHSA-N N-acetyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-N 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 208000006199 Parasomnias Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 231100000643 Substance intoxication Toxicity 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100023234 Transcription factor MafB Human genes 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 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
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229920003232 aliphatic polyester Polymers 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 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
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001639 boron compounds Chemical class 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 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
- 229940067596 butylparaben Drugs 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940078456 calcium stearate Drugs 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 235000019519 canola oil Nutrition 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 208000014486 central sleep apnea syndrome Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001793 charged compounds Chemical group 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000005959 diazepanyl group Chemical group 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
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- SZYQPTAROQANMV-UHFFFAOYSA-N ethyl pyrazine-2-carboxylate Chemical compound CCOC(=O)C1=CN=CC=N1 SZYQPTAROQANMV-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229950007535 eticlopride Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 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
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 201000001881 impotence Diseases 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
- 230000001939 inductive effect Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 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
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960003955 mianserin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- SQMJDLXORYKZGJ-UHFFFAOYSA-N n',n'-bis(methylamino)ethane-1,2-diamine Chemical compound CNN(NC)CCN SQMJDLXORYKZGJ-UHFFFAOYSA-N 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- CGJHVLKWVROWOQ-UHFFFAOYSA-N n'-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n'-[(3-fluorophenyl)methyl]-n-methylethane-1,2-diamine Chemical compound C=1C(C=2C=C3C=NNC3=CC=2)=CC=C(F)C=1CN(CCNC)CC1=CC=CC(F)=C1 CGJHVLKWVROWOQ-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- XWATUCAODJLEHY-UHFFFAOYSA-N n-(1-cyclopropylpiperidin-4-yl)-4-fluoro-n-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCN(CC1)C1CC1)CC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F XWATUCAODJLEHY-UHFFFAOYSA-N 0.000 description 1
- BWWSSMHAPVJKLD-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]benzamide Chemical compound C=1N=CC(C=2C=C3C=CNC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 BWWSSMHAPVJKLD-UHFFFAOYSA-N 0.000 description 1
- VKAXQRSLDYJESC-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-2-pyrrolidin-1-ylethanamine Chemical compound FC1=CC=C(C=2C=C3C=CNC3=CC=2)C=C1CNCCN1CCCC1 VKAXQRSLDYJESC-UHFFFAOYSA-N 0.000 description 1
- TXLFHNGNJFBLOE-UHFFFAOYSA-N n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]-n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCNCC1=CN=CC(C=2C=C3C=CNC3=CC=2)=C1 TXLFHNGNJFBLOE-UHFFFAOYSA-N 0.000 description 1
- PMTDHMKKUCNICT-JOCHJYFZSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-[(2r)-pyrrolidin-2-yl]methanamine Chemical compound C1=CC(F)=CC=C1CN(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)C[C@@H]1NCCC1 PMTDHMKKUCNICT-JOCHJYFZSA-N 0.000 description 1
- AKEUOYIUJCPBST-SDNWHVSQSA-N n-[[5-[4-[(e)-2-(dimethylamino)ethenyl]-5-nitropyridin-2-yl]-2-fluorophenyl]methyl]-4-fluoro-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=C([N+]([O-])=O)C(/C=C/N(C)C)=CC(C=2C=C(CN(CCN3CCCC3)C(=O)C=3C=CC(F)=CC=3)C(F)=CC=2)=N1 AKEUOYIUJCPBST-SDNWHVSQSA-N 0.000 description 1
- YRZNCMFHFHBVMC-UHFFFAOYSA-N n-benzyl-n',n'-dimethylpropane-1,3-diamine Chemical compound CN(C)CCCNCC1=CC=CC=C1 YRZNCMFHFHBVMC-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003887 narcotic antagonist Substances 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 125000005246 nonafluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 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
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
- 229960001999 phentolamine Drugs 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- VMPYTOIPVPQDNX-UHFFFAOYSA-N pyrrolidin-1-ylmethanamine Chemical compound NCN1CCCC1 VMPYTOIPVPQDNX-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 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
- 238000011552 rat model Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 210000002966 serum Anatomy 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
- 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
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000004620 sleep latency Effects 0.000 description 1
- 230000004622 sleep time Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 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
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ZVSSHLONWXDITD-VZUYHUTRSA-N tert-butyl (2r)-2-[[(4-fluorophenyl)methyl-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]amino]methyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1CN(CC=1C(=CC=C(C=1)C=1C=C2N=NN(C2=CC=1)C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)F)CC1=CC=C(F)C=C1 ZVSSHLONWXDITD-VZUYHUTRSA-N 0.000 description 1
- VRZPQTQRUBYMPF-OAHLLOKOSA-N tert-butyl (2r)-2-[[(4-fluorophenyl)methylamino]methyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1CNCC1=CC=C(F)C=C1 VRZPQTQRUBYMPF-OAHLLOKOSA-N 0.000 description 1
- YDBPZCVWPFMBDH-QMMMGPOBSA-N tert-butyl (2s)-2-formylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C=O YDBPZCVWPFMBDH-QMMMGPOBSA-N 0.000 description 1
- JGKNIAROXFQYGJ-LJQANCHMSA-N tert-butyl (3s)-4-[(5-bromopyridin-3-yl)methyl]-3-(4-fluorophenyl)piperazine-1-carboxylate Chemical compound C([C@@H]1C=2C=CC(F)=CC=2)N(C(=O)OC(C)(C)C)CCN1CC1=CN=CC(Br)=C1 JGKNIAROXFQYGJ-LJQANCHMSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- JGKNIAROXFQYGJ-UHFFFAOYSA-N tert-butyl 4-[(5-bromopyridin-3-yl)methyl]-3-(4-fluorophenyl)piperazine-1-carboxylate Chemical compound C=1C=C(F)C=CC=1C1CN(C(=O)OC(C)(C)C)CCN1CC1=CN=CC(Br)=C1 JGKNIAROXFQYGJ-UHFFFAOYSA-N 0.000 description 1
- BRKFYEFPVHLJSU-UHFFFAOYSA-N tert-butyl 5-[4-fluoro-3-[(3-pyrrolidin-1-ylpropylamino)methyl]phenyl]indazole-1-carboxylate Chemical compound C=1C=C2N(C(=O)OC(C)(C)C)N=CC2=CC=1C(C=1)=CC=C(F)C=1CNCCCN1CCCC1 BRKFYEFPVHLJSU-UHFFFAOYSA-N 0.000 description 1
- YYPKAUWUQZEFKC-UHFFFAOYSA-N tert-butyl 5-[4-fluoro-3-[[(3-fluorophenyl)methyl-[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethyl]amino]methyl]phenyl]indazole-1-carboxylate Chemical compound C=1C(C=2C=C3C=NN(C3=CC=2)C(=O)OC(C)(C)C)=CC=C(F)C=1CN(CCN(C)C(=O)OC(C)(C)C)CC1=CC=CC(F)=C1 YYPKAUWUQZEFKC-UHFFFAOYSA-N 0.000 description 1
- LGQOGMHZVGIYAO-UHFFFAOYSA-N tert-butyl 5-[4-fluoro-3-[[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]methyl]phenyl]indazole-1-carboxylate Chemical compound C1=C(F)C(CNCCN(C)C(=O)OC(C)(C)C)=CC(C=2C=C3C=NN(C3=CC=2)C(=O)OC(C)(C)C)=C1 LGQOGMHZVGIYAO-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QYJVBVKFXDHFPQ-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)-n-methylcarbamate Chemical compound NCCN(C)C(=O)OC(C)(C)C QYJVBVKFXDHFPQ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000003519 ventilatory effect Effects 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
- 239000003643 water by type Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65191105P | 2005-02-10 | 2005-02-10 | |
| US60/651,911 | 2005-02-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20070107037A true KR20070107037A (ko) | 2007-11-06 |
Family
ID=36577530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077018430A Withdrawn KR20070107037A (ko) | 2005-02-10 | 2006-02-10 | 선택적 5ht2a 길항제로서의 치환된 비스 아릴 및헤테로아릴 화합물 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7625889B2 (enExample) |
| EP (1) | EP1851199B1 (enExample) |
| JP (1) | JP5419355B2 (enExample) |
| KR (1) | KR20070107037A (enExample) |
| CN (1) | CN101115717A (enExample) |
| AR (1) | AR052903A1 (enExample) |
| AU (1) | AU2006213634A1 (enExample) |
| BR (1) | BRPI0606740A2 (enExample) |
| CA (1) | CA2598429A1 (enExample) |
| CR (1) | CR9260A (enExample) |
| DO (1) | DOP2006000032A (enExample) |
| GT (1) | GT200600042A (enExample) |
| IL (1) | IL185173A0 (enExample) |
| MA (1) | MA29289B1 (enExample) |
| MX (1) | MX2007008606A (enExample) |
| NO (1) | NO20074583L (enExample) |
| PA (1) | PA8662501A1 (enExample) |
| PE (1) | PE20061088A1 (enExample) |
| RU (1) | RU2007133655A (enExample) |
| TN (1) | TNSN07272A1 (enExample) |
| TW (1) | TW200640859A (enExample) |
| UY (1) | UY29372A1 (enExample) |
| WO (1) | WO2006086705A1 (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20060100T3 (en) | 2003-07-22 | 2007-03-31 | Arena Pharmaceuticals Inc | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto |
| SA05260357B1 (ar) | 2004-11-19 | 2008-09-08 | ارينا فارماسيتو تيكالز ، أنك | مشتقات 3_فينيل_بيرازول كمعدلات لمستقبل سيروتينين 5_ht2a مفيدة في علاج الاضطرابات المتعلقه به |
| ES2336142T3 (es) | 2005-08-19 | 2010-04-08 | Aventis Pharmaceuticals Inc. | Combinacion de un agente hipnotico y un compuesto sustituido, con bis arilo y heteroarilo y aplicacion terapeutica del mismo. |
| US8927546B2 (en) * | 2006-02-28 | 2015-01-06 | Dart Neuroscience (Cayman) Ltd. | Therapeutic piperazines |
| CA2644069A1 (en) * | 2006-02-28 | 2007-09-07 | Helicon Therapeutics, Inc. | Therapeutic piperazines as pde4 inhibitors |
| AR060336A1 (es) | 2006-03-31 | 2008-06-11 | Schering Corp | Derivados de indazolilpirazinilo inhibidores de proteinquinasas, composiciones farmaceuticas que los contienen y usos como agentes anticancer,entre otros. |
| CA2646076C (en) | 2006-05-18 | 2015-06-30 | Arena Pharmaceuticals, Inc. | Ethers, secondary amines and derivatives thereof as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| WO2007136689A2 (en) | 2006-05-18 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-ht2a serotonin receptor |
| USRE45336E1 (en) | 2006-05-18 | 2015-01-13 | Arena Pharmaceuticals, Inc. | Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto |
| TWI415845B (zh) | 2006-10-03 | 2013-11-21 | Arena Pharm Inc | 用於治療與5-ht2a血清素受體相關聯病症之作為5-ht2a血清素受體之調節劑的吡唑衍生物 |
| EP2190844B3 (en) | 2007-08-15 | 2013-07-17 | Arena Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| WO2009123714A2 (en) | 2008-04-02 | 2009-10-08 | Arena Pharmaceuticals, Inc. | Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor |
| EP2344480A1 (en) | 2008-10-15 | 2011-07-20 | Boehringer Ingelheim International GmbH | Fused heteroaryl diamide compounds useful as mmp-13 inhibitors |
| EP2340243B1 (en) | 2008-10-17 | 2014-10-08 | Boehringer Ingelheim International GmbH | Heteroaryl substituted indole compounds useful as mmp-13 inhibitors |
| TR201805216T4 (en) | 2008-10-28 | 2018-06-21 | Arena Pharm Inc | COMPOSITIONS OF A USEFUL 5-HT2A SEROTONINE RECEPTOR MODULATOR FOR THE TREATMENT OF RELATED DISORDERS |
| WO2010062321A1 (en) | 2008-10-28 | 2010-06-03 | Arena Pharmaceuticals, Inc. | Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea and crystalline forms related thereto |
| WO2011075596A1 (en) | 2009-12-18 | 2011-06-23 | Arena Pharmaceuticals, Inc. | Crystalline forms of certain 3-phenyl-pyrazole derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| EP2704573A4 (en) * | 2011-05-03 | 2014-10-15 | Merck Sharp & Dohme | AMINOMETHYL biaryl BENZOTRIAZOL DERIVATIVES |
| US11718643B2 (en) | 2012-11-13 | 2023-08-08 | Cytiva Bioprocess R&D Ab | Multimodal anion exchange matrices |
| KR20180011843A (ko) | 2015-06-11 | 2018-02-02 | 바실리어 파마슈티카 인터내셔널 리미티드 | 유출-펌프 억제제 및 이의 치료적 용도 |
| JP2018516992A (ja) | 2015-06-12 | 2018-06-28 | アクソファント サイエンシーズ ゲーエムベーハーAxovant Sciences Gmbh | レム睡眠行動障害の予防および処置のために有用なジアリールおよびアリールヘテロアリール尿素誘導体 |
| WO2017011767A2 (en) | 2015-07-15 | 2017-01-19 | Axovant Sciences Ltd. | Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of hallucinations associated with a neurodegenerative disease |
| CN106854189A (zh) * | 2015-12-08 | 2017-06-16 | 湖南华腾制药有限公司 | 一种哌嗪化合物的合成方法 |
| CN107778257A (zh) * | 2016-08-29 | 2018-03-09 | 湖南华腾制药有限公司 | 一种哌嗪衍生物的合成方法 |
| CN106977463A (zh) * | 2017-05-31 | 2017-07-25 | 湖南华腾制药有限公司 | 一种联苯取代哌嗪衍生物的合成方法 |
| SG11202001062XA (en) | 2017-08-21 | 2020-03-30 | Acadia Pharm Inc | Compounds, salts thereof and methods for treatment of diseases |
| WO2019040104A2 (en) * | 2017-08-21 | 2019-02-28 | Acadia Pharmaceuticals Inc. | COMPOUNDS, RELATED SALTS AND METHODS OF TREATING DISEASES |
| WO2021038419A1 (en) * | 2019-08-23 | 2021-03-04 | Insilico Medicine Ip Limited | Kinase inhibitors and methods of synthesis and treatment |
| US12293809B2 (en) | 2019-08-23 | 2025-05-06 | Insilico Medicine Ip Limited | Workflow for generating compounds with biological activity against a specific biological target |
| WO2022249113A1 (ko) * | 2021-05-25 | 2022-12-01 | 주식회사 자이메디 | Aimp2-dx2와 kras의 결합을 억제하는 신규 화합물 및 이의 용도 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8305245D0 (en) * | 1983-02-25 | 1983-03-30 | Fujisawa Pharmaceutical Co | Imidazo-heterocyclic compounds |
| GB9114760D0 (en) * | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| DE69910795T2 (de) * | 1998-06-09 | 2004-06-17 | Takeda Chemical Industries, Ltd. | Pharmazeutische kombination mit einer trizyclischen verbindung und mindestens einer von zolpidem, zopiclone und brotizolam, zur behandlung oder verhinderung von schlafstörungen |
| MXPA02000537A (es) * | 1999-07-16 | 2004-09-10 | Bristol Myers Squibb Pharma Co | Heterobiciclos que contienen nitrogeno como inhibidores del factor xa. |
| DE19934433A1 (de) * | 1999-07-22 | 2001-01-25 | Merck Patent Gmbh | N-(Indolcarbonyl-)piperazinderivate |
| US6573049B1 (en) * | 1999-07-26 | 2003-06-03 | Nuvelo, Inc. | Genotyping of the paraoxonase 1 gene for prognosing, diagnosing, and treating a disease |
| YU54202A (sh) * | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| EP1345935A2 (en) * | 2000-12-21 | 2003-09-24 | Warner-Lambert Company LLC | Piperidine derivatives as subtype selective n-methyl-d-aspartate antagonists |
| DE10209520A1 (de) * | 2002-03-04 | 2003-09-25 | 4Sc Ag | Neue Modulatoren von Kaliumkanälen |
| US7342115B2 (en) * | 2002-11-08 | 2008-03-11 | Neurogen Corporation | 3-substituted-6-aryl pyridines |
| DK1603570T5 (da) * | 2003-02-26 | 2013-12-09 | Sugen Inc | Aminoheteroarylforbindelser som proteinkinaseinhibitorer |
| EP1599475A2 (en) * | 2003-03-06 | 2005-11-30 | Eisai Co., Ltd. | Jnk inhibitors |
| EP1678144A1 (en) * | 2003-10-23 | 2006-07-12 | Akzo Nobel N.V. | 1,5,7-TRISUBSTITUTED BENZIMIDAZOLE DERIVATIVES AND THEIR USE FOR MODULATING THE GABA-a RECEPTOR COMPLEX |
| MXPA06011167A (es) * | 2004-04-01 | 2007-01-25 | Eli Lilli And Company | Agentes del receptor h3 de histamina, preparacion y usos terapeuticos. |
| US20060014733A1 (en) * | 2004-07-19 | 2006-01-19 | Pfizer Inc | Histamine-3 agonists and antagonists |
| JP2008508314A (ja) * | 2004-07-28 | 2008-03-21 | アイアールエム・リミテッド・ライアビリティ・カンパニー | ステロイドホルモン核内受容体のモジュレーターとしての化合物および組成物 |
-
2006
- 2006-02-06 GT GT200600042A patent/GT200600042A/es unknown
- 2006-02-07 DO DO2006000032A patent/DOP2006000032A/es unknown
- 2006-02-08 PE PE2006000149A patent/PE20061088A1/es not_active Application Discontinuation
- 2006-02-10 BR BRPI0606740-9A patent/BRPI0606740A2/pt not_active Application Discontinuation
- 2006-02-10 PA PA20068662501A patent/PA8662501A1/es unknown
- 2006-02-10 RU RU2007133655/04A patent/RU2007133655A/ru not_active Application Discontinuation
- 2006-02-10 AU AU2006213634A patent/AU2006213634A1/en not_active Abandoned
- 2006-02-10 MX MX2007008606A patent/MX2007008606A/es not_active Application Discontinuation
- 2006-02-10 TW TW095104456A patent/TW200640859A/zh unknown
- 2006-02-10 JP JP2007555276A patent/JP5419355B2/ja not_active Expired - Fee Related
- 2006-02-10 CN CNA200680004616XA patent/CN101115717A/zh active Pending
- 2006-02-10 CA CA002598429A patent/CA2598429A1/en not_active Abandoned
- 2006-02-10 UY UY29372A patent/UY29372A1/es unknown
- 2006-02-10 KR KR1020077018430A patent/KR20070107037A/ko not_active Withdrawn
- 2006-02-10 WO PCT/US2006/004879 patent/WO2006086705A1/en not_active Ceased
- 2006-02-10 EP EP06734836A patent/EP1851199B1/en active Active
- 2006-10-09 AR ARP060100467A patent/AR052903A1/es not_active Application Discontinuation
-
2007
- 2007-07-13 TN TNP2007000272A patent/TNSN07272A1/en unknown
- 2007-07-19 CR CR9260A patent/CR9260A/es not_active Application Discontinuation
- 2007-07-25 US US11/782,923 patent/US7625889B2/en active Active
- 2007-08-09 IL IL185173A patent/IL185173A0/en unknown
- 2007-08-31 MA MA30191A patent/MA29289B1/fr unknown
- 2007-09-10 NO NO20074583A patent/NO20074583L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DOP2006000032A (es) | 2006-08-15 |
| CR9260A (es) | 2007-10-04 |
| JP5419355B2 (ja) | 2014-02-19 |
| NO20074583L (no) | 2007-10-12 |
| EP1851199A1 (en) | 2007-11-07 |
| TW200640859A (en) | 2006-12-01 |
| PE20061088A1 (es) | 2006-11-29 |
| BRPI0606740A2 (pt) | 2009-07-14 |
| WO2006086705B1 (en) | 2006-11-16 |
| US7625889B2 (en) | 2009-12-01 |
| IL185173A0 (en) | 2007-12-03 |
| RU2007133655A (ru) | 2009-03-20 |
| EP1851199B1 (en) | 2012-05-16 |
| WO2006086705A1 (en) | 2006-08-17 |
| TNSN07272A1 (en) | 2008-12-31 |
| PA8662501A1 (es) | 2006-09-08 |
| AU2006213634A1 (en) | 2006-08-17 |
| AR052903A1 (es) | 2007-04-11 |
| GT200600042A (es) | 2006-09-27 |
| CA2598429A1 (en) | 2006-08-17 |
| JP2008530120A (ja) | 2008-08-07 |
| UY29372A1 (es) | 2006-10-02 |
| US20070265309A1 (en) | 2007-11-15 |
| CN101115717A (zh) | 2008-01-30 |
| MX2007008606A (es) | 2007-09-11 |
| MA29289B1 (fr) | 2008-02-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20070107037A (ko) | 선택적 5ht2a 길항제로서의 치환된 비스 아릴 및헤테로아릴 화합물 | |
| CN103339111B (zh) | 双环乙酰基-CoA羧化酶抑制剂 | |
| JP4754821B2 (ja) | 肥満症、ii型糖尿病およびcns障害の治療に有用な新規化合物 | |
| EP2678331B1 (en) | Diaminopyrimidine derivatives and processes for the preparation thereof | |
| TWI833773B (zh) | 化合物 | |
| US5300506A (en) | Indolylalkyl derivatives of pyrimidinylpiperazine for treating vascular headache | |
| WO2007063934A1 (ja) | 脂環式複素環化合物 | |
| JP2002524512A (ja) | cGMPホスホジエステラーゼの縮合ピリジン阻害剤 | |
| DE69128231T2 (de) | Heterozyklische Alkylamine, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen die sie enthalten | |
| JP2003513088A (ja) | アリールアルカン、アリールアルケン及びアリール−アザアルカン、これら化合物を含有する製薬組成物及びその調製方法 | |
| US7618650B2 (en) | Combination of a hypnotic agent and substituted bis aryl and heteroaryl compound and therapeutic application thereof | |
| NO314996B1 (no) | Derivater av acylpiperazinylpyrimidiner, farmasöytisk preparat inneholdendeslike derivater, deres fremstilling, og anvendelse tilfremstilling av legemidler | |
| TW201625581A (zh) | 側氧雜環衍生物 | |
| WO2007063935A1 (ja) | 芳香族化合物 | |
| EA035406B1 (ru) | Соединения пиридиния | |
| KR100743255B1 (ko) | T-형 칼슘 채널에 활성을 지닌 신규1,3-다이옥소아이소인돌 유도체 | |
| WO1993010089A1 (fr) | Nouveaux composes d'amide et utilisation de ces composes comme medicaments | |
| WO2014104209A1 (ja) | 新規ベンゾアゼピン誘導体及びその医薬用途 | |
| HK1113789A (en) | Substituted bis aryl and heteroaryl compounds as selective 5ht2a antagonists | |
| RU2587981C2 (ru) | Производные диаминопиримидина и способы их получения | |
| HK1121673A (en) | Combination of a hypnotic agent and substituted bis aryl and heteroaryl compound and therapeutic application thereof | |
| JPWO1999050264A1 (ja) | キナゾリン誘導体 | |
| JPWO2007063934A1 (ja) | 脂環式複素環化合物 | |
| JPWO1999055674A1 (ja) | 1−[(1−置換−4−ピペリジニル)メチル]−4−ピペリジン誘導体、その製造方法、それを含有する医薬組成物および該化合物の中間体 | |
| HK1105196B (en) | 3-SUBSTITUTED-5- AND 6-AMINOALKYL INDOLE-2-CARBOXYLIC ACID AMIDES AND RELATED ANALOGS AS INHIBITORS OF CASEIN KINASE Iε |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20070810 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |