KR20100014413A

KR20100014413A - 5-ｈｔ6 수용체 친화력을 갖는 6' 치환된 인돌 및 인다졸 유도체

5-ｈｔ6 수용체 친화력을 갖는 6' 치환된 인돌 및 인다졸 유도체 Download PDF

Info

Publication number: KR20100014413A
Authority: KR; South Korea
Prior art keywords: sulfonyl; piperazin; methyl; indazole; indole
Prior art date: 2007-02-16
Legal status : Withdrawn

Application number

KR1020097019250A

Other languages

English (en)

Korean (ko)

Inventor

로버트 던

트룩 민 구이엔

웽 지에

애쇽 테힘

Original Assignee

메모리 파마슈티칼스 코포레이션

Priority date

2007-02-16

Filing date

2008-02-19

Publication date

2010-02-10

2008-02-19 Application filed by 메모리 파마슈티칼스 코포레이션 filed Critical 메모리 파마슈티칼스 코포레이션

2010-02-10 Publication of KR20100014413A publication Critical patent/KR20100014413A/ko

Status Withdrawn legal-status Critical Current

Links

SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 17
108091005435 5-HT6 receptors Proteins 0.000 title abstract description 23
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title description 7
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title description 7
150000002473 indoazoles Chemical class 0.000 title 1
150000002475 indoles Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 164
238000000034 method Methods 0.000 claims abstract description 92
-1 cyano, hydroxy Chemical group 0.000 claims description 217
125000000217 alkyl group Chemical group 0.000 claims description 49
125000004432 carbon atom Chemical group C* 0.000 claims description 49
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 47
229910052736 halogen Inorganic materials 0.000 claims description 45
150000002367 halogens Chemical class 0.000 claims description 45
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 39
238000011282 treatment Methods 0.000 claims description 39
229920006395 saturated elastomer Polymers 0.000 claims description 27
208000035475 disorder Diseases 0.000 claims description 24
238000002360 preparation method Methods 0.000 claims description 23
208000023105 Huntington disease Diseases 0.000 claims description 22
201000000980 schizophrenia Diseases 0.000 claims description 22
239000010432 diamond Substances 0.000 claims description 20
229910003460 diamond Inorganic materials 0.000 claims description 20
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 19
208000018737 Parkinson disease Diseases 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
125000000623 heterocyclic group Chemical group 0.000 claims description 18
125000006413 ring segment Chemical group 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 17
125000000753 cycloalkyl group Chemical group 0.000 claims description 17
125000004043 oxo group Chemical group O=* 0.000 claims description 17
239000000126 substance Substances 0.000 claims description 17
206010027175 memory impairment Diseases 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
208000024827 Alzheimer disease Diseases 0.000 claims description 15
208000010877 cognitive disease Diseases 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
208000028698 Cognitive impairment Diseases 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
208000002551 irritable bowel syndrome Diseases 0.000 claims description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
239000012453 solvate Substances 0.000 claims description 11
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 10
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 10
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
206010019196 Head injury Diseases 0.000 claims description 9
229910052786 argon Inorganic materials 0.000 claims description 9
206010015037 epilepsy Diseases 0.000 claims description 9
230000002496 gastric effect Effects 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
125000004430 oxygen atom Chemical group O* 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
125000004434 sulfur atom Chemical group 0.000 claims description 9
208000028017 Psychotic disease Diseases 0.000 claims description 8
210000003169 central nervous system Anatomy 0.000 claims description 8
208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
206010010774 Constipation Diseases 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 claims description 6
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 6
201000011240 Frontotemporal dementia Diseases 0.000 claims description 6
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 6
208000000609 Pick Disease of the Brain Diseases 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
208000015114 central nervous system disease Diseases 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 6
208000014674 injury Diseases 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
210000000278 spinal cord Anatomy 0.000 claims description 6
208000024172 Cardiovascular disease Diseases 0.000 claims description 5
230000007000 age related cognitive decline Effects 0.000 claims description 5
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
208000011117 substance-related disease Diseases 0.000 claims description 5
230000008733 trauma Effects 0.000 claims description 5
FPEVBJQZBQEUGQ-UHFFFAOYSA-N 1-[5-(6-piperazin-1-ylindol-1-yl)sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 FPEVBJQZBQEUGQ-UHFFFAOYSA-N 0.000 claims description 4
JTTZZROAYPUWGA-FQEVSTJZSA-N 3-ethyl-1-[3-[(3s)-3-methoxypyrrolidin-1-yl]phenyl]sulfonyl-6-piperazin-1-ylindazole Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3C[C@H](CC3)OC)C2=CC=1N1CCNCC1 JTTZZROAYPUWGA-FQEVSTJZSA-N 0.000 claims description 4
OHPUUSZZEPAKHA-UHFFFAOYSA-N 7-(6-piperazin-1-ylindol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2NC(=O)COC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 OHPUUSZZEPAKHA-UHFFFAOYSA-N 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 4
208000032841 Bulimia Diseases 0.000 claims description 4
206010006550 Bulimia nervosa Diseases 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
208000030814 Eating disease Diseases 0.000 claims description 4
208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
208000019695 Migraine disease Diseases 0.000 claims description 4
206010027951 Mood swings Diseases 0.000 claims description 4
208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 4
208000022531 anorexia Diseases 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
206010061428 decreased appetite Diseases 0.000 claims description 4
125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
235000014632 disordered eating Nutrition 0.000 claims description 4
FIHOYIFGQDQURJ-UHFFFAOYSA-N ethyl 1-(benzenesulfonyl)-6-(4-methylpiperazin-1-yl)indazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=CC=CC=3)C2=CC=1N1CCN(C)CC1 FIHOYIFGQDQURJ-UHFFFAOYSA-N 0.000 claims description 4
125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 4
206010027599 migraine Diseases 0.000 claims description 4
208000019116 sleep disease Diseases 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
206010012735 Diarrhoea Diseases 0.000 claims description 3
230000007423 decrease Effects 0.000 claims description 3
GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 3
ADTDIWLBMBAJKV-NRFANRHFSA-N (3s)-1-[3-(3-ethyl-6-piperazin-1-ylindol-1-yl)sulfonylphenyl]pyrrolidin-3-ol Chemical compound C=1C=C2C(CC)=CN(S(=O)(=O)C=3C=C(C=CC=3)N3C[C@@H](O)CC3)C2=CC=1N1CCNCC1 ADTDIWLBMBAJKV-NRFANRHFSA-N 0.000 claims description 2
PBSVMXJGADSKDH-UHFFFAOYSA-N 1-(1-benzofuran-5-ylsulfonyl)-6-(4-methylpiperazin-1-yl)pyrrolo[2,3-b]pyridine Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=C4C=COC4=CC=3)C2=N1 PBSVMXJGADSKDH-UHFFFAOYSA-N 0.000 claims description 2
LQPDXJDPJIHYGM-UHFFFAOYSA-N 1-(1-methylindol-5-yl)sulfonyl-6-piperazin-1-ylindole Chemical compound C=1C=C2N(C)C=CC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 LQPDXJDPJIHYGM-UHFFFAOYSA-N 0.000 claims description 2
JCEBDUAQPWSJIB-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-6-piperazin-1-ylindazole Chemical compound C=1C=C2OCCOC2=CC=1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 JCEBDUAQPWSJIB-UHFFFAOYSA-N 0.000 claims description 2
UIHORGBXMUBBTH-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-6-piperazin-1-ylindole Chemical compound C=1C=C2OCCOC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 UIHORGBXMUBBTH-UHFFFAOYSA-N 0.000 claims description 2
TXSYYVSCELWWGU-UHFFFAOYSA-N 1-(2,4-difluorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 TXSYYVSCELWWGU-UHFFFAOYSA-N 0.000 claims description 2
JSUXIDAHSGHRSP-UHFFFAOYSA-N 1-(2,4-difluorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound FC1=CC(F)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 JSUXIDAHSGHRSP-UHFFFAOYSA-N 0.000 claims description 2
DWJJIOBNTJEODI-UHFFFAOYSA-N 1-(2,5-difluorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound FC1=CC=C(F)C(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCNCC2)=C1 DWJJIOBNTJEODI-UHFFFAOYSA-N 0.000 claims description 2
YORNGFATOLBRRJ-UHFFFAOYSA-N 1-(2,5-difluorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound FC1=CC=C(F)C(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 YORNGFATOLBRRJ-UHFFFAOYSA-N 0.000 claims description 2
UPXIKUHHXPWQCA-UHFFFAOYSA-N 1-(2,5-dimethoxyphenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound COC1=CC=C(OC)C(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCNCC2)=C1 UPXIKUHHXPWQCA-UHFFFAOYSA-N 0.000 claims description 2
OGSXIODMEFHLRL-UHFFFAOYSA-N 1-(2,5-dimethoxyphenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound COC1=CC=C(OC)C(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 OGSXIODMEFHLRL-UHFFFAOYSA-N 0.000 claims description 2
PVSOOIKNRXXNPI-UHFFFAOYSA-N 1-(2-chlorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound ClC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 PVSOOIKNRXXNPI-UHFFFAOYSA-N 0.000 claims description 2
BHCYSPJSGWDOOV-UHFFFAOYSA-N 1-(2-chlorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound ClC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 BHCYSPJSGWDOOV-UHFFFAOYSA-N 0.000 claims description 2
MZCPCTDCNNJWCC-UHFFFAOYSA-N 1-(2-fluorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound FC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 MZCPCTDCNNJWCC-UHFFFAOYSA-N 0.000 claims description 2
ABOPQOOKESSZDQ-UHFFFAOYSA-N 1-(2-fluorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound FC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 ABOPQOOKESSZDQ-UHFFFAOYSA-N 0.000 claims description 2
JHYJNNNTOHMKGI-UHFFFAOYSA-N 1-(2-methoxyphenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound COC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 JHYJNNNTOHMKGI-UHFFFAOYSA-N 0.000 claims description 2
UUZSYDKDHCABIQ-UHFFFAOYSA-N 1-(2-methoxyphenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound COC1=CC=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 UUZSYDKDHCABIQ-UHFFFAOYSA-N 0.000 claims description 2
WXDDYANVEPWXPK-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 WXDDYANVEPWXPK-UHFFFAOYSA-N 0.000 claims description 2
NILMYVRUBSALSA-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 NILMYVRUBSALSA-UHFFFAOYSA-N 0.000 claims description 2
RHUWJQJIWGRZSB-UHFFFAOYSA-N 1-(3-chlorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound ClC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCNCC2)=C1 RHUWJQJIWGRZSB-UHFFFAOYSA-N 0.000 claims description 2
IGMPPSBLAYJPSR-UHFFFAOYSA-N 1-(3-chlorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound ClC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 IGMPPSBLAYJPSR-UHFFFAOYSA-N 0.000 claims description 2
JZXRJJCQCVSTPP-UHFFFAOYSA-N 1-(3-fluorophenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound FC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCNCC2)=C1 JZXRJJCQCVSTPP-UHFFFAOYSA-N 0.000 claims description 2
BHQAIVKFNDVAPK-UHFFFAOYSA-N 1-(3-fluorophenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound FC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 BHQAIVKFNDVAPK-UHFFFAOYSA-N 0.000 claims description 2
ALYLEASIAJLDBX-UHFFFAOYSA-N 1-(3-methoxyphenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound COC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCNCC2)=C1 ALYLEASIAJLDBX-UHFFFAOYSA-N 0.000 claims description 2
JAIIGEQOPCQWAG-UHFFFAOYSA-N 1-(3-methoxyphenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound COC1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 JAIIGEQOPCQWAG-UHFFFAOYSA-N 0.000 claims description 2
RZVXKPIPNJZLHT-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-6-piperazin-1-ylindazole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=N1 RZVXKPIPNJZLHT-UHFFFAOYSA-N 0.000 claims description 2
GZZIABFQFUTFAP-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-6-piperazin-1-ylindole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=CC(N3CCNCC3)=CC=C2C=C1 GZZIABFQFUTFAP-UHFFFAOYSA-N 0.000 claims description 2
HGNIYWKFPXYKPZ-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-ethyl-6-(4-methylpiperazin-1-yl)indazole Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=CC=CC=3)C2=CC=1N1CCN(C)CC1 HGNIYWKFPXYKPZ-UHFFFAOYSA-N 0.000 claims description 2
OPBLPJLFVJLIOK-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-ethyl-6-piperazin-1-ylindazole Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=CC=CC=3)C2=CC=1N1CCNCC1 OPBLPJLFVJLIOK-UHFFFAOYSA-N 0.000 claims description 2
LWTJQRDPEPNEGQ-UHFFFAOYSA-N 1-(benzenesulfonyl)-6-(4-methylpiperazin-1-yl)indazole-3-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC=C(C(=NN2S(=O)(=O)C=3C=CC=CC=3)C(O)=O)C2=C1 LWTJQRDPEPNEGQ-UHFFFAOYSA-N 0.000 claims description 2
ZZRPBEZGINGVMX-UHFFFAOYSA-N 1-(benzenesulfonyl)-6-(4-methylpiperazin-1-yl)indole Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=CC=CC=3)C2=C1 ZZRPBEZGINGVMX-UHFFFAOYSA-N 0.000 claims description 2
RTGJTPRVJSBLFD-UHFFFAOYSA-N 1-(benzenesulfonyl)-6-piperazin-1-ylindole Chemical compound C1=CC2=CC=C(N3CCNCC3)C=C2N1S(=O)(=O)C1=CC=CC=C1 RTGJTPRVJSBLFD-UHFFFAOYSA-N 0.000 claims description 2
KQBDABKQHCVIOK-UHFFFAOYSA-N 1-[3-(3-ethyl-6-piperazin-1-ylindazol-1-yl)sulfonylphenyl]pyrrolidin-3-ol Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(O)CC3)C2=CC=1N1CCNCC1 KQBDABKQHCVIOK-UHFFFAOYSA-N 0.000 claims description 2
JPJKFVCJTBXCSV-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)indazole Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=N2)N2CCN(C)CC2)=C1 JPJKFVCJTBXCSV-UHFFFAOYSA-N 0.000 claims description 2
LBIQENJTASNXQV-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)indole Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCN(C)CC2)=C1 LBIQENJTASNXQV-UHFFFAOYSA-N 0.000 claims description 2
KXOFVOJELSIXOU-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)pyrazolo[3,4-b]pyridine Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=NC(=CC=C3C=N2)N2CCN(C)CC2)=C1 KXOFVOJELSIXOU-UHFFFAOYSA-N 0.000 claims description 2
IIACDKWDBOSBHI-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)pyrrolo[2,3-b]pyridine Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=NC(=CC=C3C=C2)N2CCN(C)CC2)=C1 IIACDKWDBOSBHI-UHFFFAOYSA-N 0.000 claims description 2
NIKGJIHOYXJKKP-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-piperazin-1-ylindole Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CCNCC2)=C1 NIKGJIHOYXJKKP-UHFFFAOYSA-N 0.000 claims description 2
JDCDWRVYLFBQJB-UHFFFAOYSA-N 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-piperazin-1-ylpyrazolo[3,4-b]pyridine Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=NC(=CC=C3C=N2)N2CCNCC2)=C1 JDCDWRVYLFBQJB-UHFFFAOYSA-N 0.000 claims description 2
PMFOAOBYVVLKED-FQEVSTJZSA-N 1-[3-[(3s)-3-methoxypyrrolidin-1-yl]phenyl]sulfonyl-3-methyl-6-piperazin-1-ylindazole Chemical compound C1[C@@H](OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C(C)=N2)N2CCNCC2)=C1 PMFOAOBYVVLKED-FQEVSTJZSA-N 0.000 claims description 2
SNPGIQRSFYALIF-NRFANRHFSA-N 1-[3-[(3s)-3-methoxypyrrolidin-1-yl]phenyl]sulfonyl-3-methyl-6-piperazin-1-ylindole Chemical compound C1[C@@H](OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C(C)=C2)N2CCNCC2)=C1 SNPGIQRSFYALIF-NRFANRHFSA-N 0.000 claims description 2
OGDHHBWNUBKISC-UHFFFAOYSA-N 1-[3-[3-ethyl-6-(4-methylpiperazin-1-yl)indazol-1-yl]sulfonylphenyl]pyrrolidin-3-ol Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(O)CC3)C2=CC=1N1CCN(C)CC1 OGDHHBWNUBKISC-UHFFFAOYSA-N 0.000 claims description 2
TTYFOZJVVOCZPF-UHFFFAOYSA-N 1-[5-(3-ethyl-6-piperazin-1-ylindazol-1-yl)sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C4CCN(C4=CC=3)C(C)=O)C2=CC=1N1CCNCC1 TTYFOZJVVOCZPF-UHFFFAOYSA-N 0.000 claims description 2
TZIHAMMSUVQTHM-UHFFFAOYSA-N 1-[5-[6-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)indol-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C1CN2CCCC2CN1C(C=C12)=CC=C2C=CN1S(=O)(=O)C1=CC=C2N(C(=O)C)CCC2=C1 TZIHAMMSUVQTHM-UHFFFAOYSA-N 0.000 claims description 2
DZPGWWPFCLDAQA-UHFFFAOYSA-N 1-[5-[6-(4-methylpiperazin-1-yl)indazol-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C1CN(C)CCN1C1=CC=C(C=NN2S(=O)(=O)C=3C=C4CCN(C4=CC=3)C(C)=O)C2=C1 DZPGWWPFCLDAQA-UHFFFAOYSA-N 0.000 claims description 2
RTFPDAXYNHVKQF-UHFFFAOYSA-N 1-[5-[6-(4-methylpiperazin-1-yl)indol-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=C4CCN(C4=CC=3)C(C)=O)C2=C1 RTFPDAXYNHVKQF-UHFFFAOYSA-N 0.000 claims description 2
DJTCSDNIVVNPDS-UHFFFAOYSA-N 1-[5-[6-(4-methylpiperazin-1-yl)pyrazolo[3,4-b]pyridin-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C1CN(C)CCN1C1=CC=C(C=NN2S(=O)(=O)C=3C=C4CCN(C4=CC=3)C(C)=O)C2=N1 DJTCSDNIVVNPDS-UHFFFAOYSA-N 0.000 claims description 2
JZLOELSFEGYFHY-UHFFFAOYSA-N 1-[5-[6-(4-methylpiperazin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=C4CCN(C4=CC=3)C(C)=O)C2=N1 JZLOELSFEGYFHY-UHFFFAOYSA-N 0.000 claims description 2
SGBPGVWCKJFVJP-UHFFFAOYSA-N 1-naphthalen-1-ylsulfonyl-6-piperazin-1-ylindazole Chemical compound C=1C=CC2=CC=CC=C2C=1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 SGBPGVWCKJFVJP-UHFFFAOYSA-N 0.000 claims description 2
CKTDTQQTSNHDLA-UHFFFAOYSA-N 1-naphthalen-1-ylsulfonyl-6-piperazin-1-ylindole Chemical compound C=1C=CC2=CC=CC=C2C=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 CKTDTQQTSNHDLA-UHFFFAOYSA-N 0.000 claims description 2
KZNZFOHVHSWWBD-UHFFFAOYSA-N 2-[1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonylindol-6-yl]-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CC3CCCN3CC2)=C1 KZNZFOHVHSWWBD-UHFFFAOYSA-N 0.000 claims description 2
MKGWLUAOBJHNRW-UHFFFAOYSA-N 3-(6-piperazin-1-ylindazol-1-yl)sulfonylbenzonitrile Chemical compound N1=CC2=CC=C(N3CCNCC3)C=C2N1S(=O)(=O)C1=CC=CC(C#N)=C1 MKGWLUAOBJHNRW-UHFFFAOYSA-N 0.000 claims description 2
QZNHFFLBMVNPKI-UHFFFAOYSA-N 3-(6-piperazin-1-ylindazol-1-yl)sulfonylquinoline Chemical compound C=1N=C2C=CC=CC2=CC=1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 QZNHFFLBMVNPKI-UHFFFAOYSA-N 0.000 claims description 2
FHKFIVASTGCWIQ-UHFFFAOYSA-N 3-(6-piperazin-1-ylindol-1-yl)sulfonylbenzonitrile Chemical compound C1=CC2=CC=C(N3CCNCC3)C=C2N1S(=O)(=O)C1=CC=CC(C#N)=C1 FHKFIVASTGCWIQ-UHFFFAOYSA-N 0.000 claims description 2
PTLZENXSHMYLOB-UHFFFAOYSA-N 3-(6-piperazin-1-ylindol-1-yl)sulfonylquinoline Chemical compound C=1N=C2C=CC=CC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 PTLZENXSHMYLOB-UHFFFAOYSA-N 0.000 claims description 2
XTYRVWOSJXRHPJ-UHFFFAOYSA-N 3-ethyl-1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)indazole Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(CC3)OC)C2=CC=1N1CCN(C)CC1 XTYRVWOSJXRHPJ-UHFFFAOYSA-N 0.000 claims description 2
JTTZZROAYPUWGA-UHFFFAOYSA-N 3-ethyl-1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-piperazin-1-ylindazole Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(CC3)OC)C2=CC=1N1CCNCC1 JTTZZROAYPUWGA-UHFFFAOYSA-N 0.000 claims description 2
HEZDQQNTXXEXNB-QFIPXVFZSA-N 3-ethyl-1-[3-[(3s)-3-methoxypyrrolidin-1-yl]phenyl]sulfonyl-6-piperazin-1-ylindole Chemical compound C=1C=C2C(CC)=CN(S(=O)(=O)C=3C=C(C=CC=3)N3C[C@H](CC3)OC)C2=CC=1N1CCNCC1 HEZDQQNTXXEXNB-QFIPXVFZSA-N 0.000 claims description 2
ZRQHMTAXOQJDAL-UHFFFAOYSA-N 4-methyl-6-(3-methyl-6-piperazin-1-ylindazol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C2N(C)CCOC2=CC=C1S(=O)(=O)N(C1=C2)N=C(C)C1=CC=C2N1CCNCC1 ZRQHMTAXOQJDAL-UHFFFAOYSA-N 0.000 claims description 2
LDIVZZXDUNBTOQ-UHFFFAOYSA-N 4-methyl-6-(3-methyl-6-piperazin-1-ylindol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C2N(C)CCOC2=CC=C1S(=O)(=O)N(C1=C2)C=C(C)C1=CC=C2N1CCNCC1 LDIVZZXDUNBTOQ-UHFFFAOYSA-N 0.000 claims description 2
QCWJROWCGBTZJM-UHFFFAOYSA-N 4-methyl-6-(6-piperazin-1-ylindazol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C2N(C)CCOC2=CC=C1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 QCWJROWCGBTZJM-UHFFFAOYSA-N 0.000 claims description 2
RALDUNJRVXFKFV-UHFFFAOYSA-N 4-methyl-6-(6-piperazin-1-ylindol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C2N(C)CCOC2=CC=C1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 RALDUNJRVXFKFV-UHFFFAOYSA-N 0.000 claims description 2
QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 claims description 2
ITHQXMSFQLJNKS-UHFFFAOYSA-N 4-methyl-7-(6-piperazin-1-ylindazol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 ITHQXMSFQLJNKS-UHFFFAOYSA-N 0.000 claims description 2
WZVWCLBDNOYPSB-UHFFFAOYSA-N 4-methyl-7-(6-piperazin-1-ylindol-1-yl)sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 WZVWCLBDNOYPSB-UHFFFAOYSA-N 0.000 claims description 2
AQISMXNYQCWMJY-UHFFFAOYSA-N 4-methyl-7-[6-(4-methylpiperazin-1-yl)pyrazolo[3,4-b]pyridin-1-yl]sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1CN(C)CCN1C1=CC=C(C=NN2S(=O)(=O)C=3C=C4OCCN(C)C4=CC=3)C2=N1 AQISMXNYQCWMJY-UHFFFAOYSA-N 0.000 claims description 2
VYXTXKFOSQMZJZ-UHFFFAOYSA-N 4-methyl-7-[6-(4-methylpiperazin-1-yl)pyrrolo[2,3-b]pyridin-1-yl]sulfonyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=C4OCCN(C)C4=CC=3)C2=N1 VYXTXKFOSQMZJZ-UHFFFAOYSA-N 0.000 claims description 2
LJZJGUXMNAXKRI-UHFFFAOYSA-N 5-(6-piperazin-1-ylindol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=12NC(=O)COC2=CC=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 LJZJGUXMNAXKRI-UHFFFAOYSA-N 0.000 claims description 2
VYHYOZHUTZEUNP-UHFFFAOYSA-N 6-(3-ethyl-6-piperazin-1-ylindol-1-yl)sulfonyl-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2C(CC)=CN(S(=O)(=O)C=3C=C4N(C)CCOC4=CC=3)C2=CC=1N1CCNCC1 VYHYOZHUTZEUNP-UHFFFAOYSA-N 0.000 claims description 2
JCGZGOMNFAHERU-UHFFFAOYSA-N 6-(3-ethyl-6-piperazin-1-ylindol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2C(CC)=CN(S(=O)(=O)C=3C=C4NC(=O)COC4=CC=3)C2=CC=1N1CCNCC1 JCGZGOMNFAHERU-UHFFFAOYSA-N 0.000 claims description 2
BVZWWXVUMWWUCI-UHFFFAOYSA-N 6-(3-methyl-6-piperazin-1-ylindazol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2C(C)=NN(S(=O)(=O)C=3C=C4NC(=O)COC4=CC=3)C2=CC=1N1CCNCC1 BVZWWXVUMWWUCI-UHFFFAOYSA-N 0.000 claims description 2
HAEHHDMCOVEJGW-UHFFFAOYSA-N 6-(3-methyl-6-piperazin-1-ylindol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2C(C)=CN(S(=O)(=O)C=3C=C4NC(=O)COC4=CC=3)C2=CC=1N1CCNCC1 HAEHHDMCOVEJGW-UHFFFAOYSA-N 0.000 claims description 2
BFQPNPXADIPZNW-UHFFFAOYSA-N 6-(6-piperazin-1-ylindazol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)COC2=CC=C1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 BFQPNPXADIPZNW-UHFFFAOYSA-N 0.000 claims description 2
GHGJGGGBOGGGDD-UHFFFAOYSA-N 6-(6-piperazin-1-ylindol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)COC2=CC=C1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 GHGJGGGBOGGGDD-UHFFFAOYSA-N 0.000 claims description 2
YCNURPYTJNOQOS-UHFFFAOYSA-N 7-(3-ethyl-6-piperazin-1-ylindazol-1-yl)sulfonyl-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C4OCCN(C)C4=CC=3)C2=CC=1N1CCNCC1 YCNURPYTJNOQOS-UHFFFAOYSA-N 0.000 claims description 2
ADGZKLHFAPYYBF-UHFFFAOYSA-N 7-(3-ethyl-6-piperazin-1-ylindazol-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2C(CC)=NN(S(=O)(=O)C=3C=C4OCC(=O)NC4=CC=3)C2=CC=1N1CCNCC1 ADGZKLHFAPYYBF-UHFFFAOYSA-N 0.000 claims description 2
PYWYRDCJHXBKDW-UHFFFAOYSA-N 7-(6-piperazin-1-ylpyrazolo[3,4-b]pyridin-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C=1C=C2NC(=O)COC2=CC=1S(=O)(=O)N(C1=N2)N=CC1=CC=C2N1CCNCC1 PYWYRDCJHXBKDW-UHFFFAOYSA-N 0.000 claims description 2
WPGIKMOWAWRHNZ-UHFFFAOYSA-N 7-[6-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)indol-1-yl]sulfonyl-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1CN2CCCC2CN1C(C=C12)=CC=C2C=CN1S(=O)(=O)C1=CC=C2N(C)CCOC2=C1 WPGIKMOWAWRHNZ-UHFFFAOYSA-N 0.000 claims description 2
OZNNNZGPWZQTKE-UHFFFAOYSA-N 7-[6-(4-methylpiperazin-1-yl)indazol-1-yl]sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C1CN(C)CCN1C1=CC=C(C=NN2S(=O)(=O)C=3C=C4OCC(=O)NC4=CC=3)C2=C1 OZNNNZGPWZQTKE-UHFFFAOYSA-N 0.000 claims description 2
MYKIMDOOFLINFA-UHFFFAOYSA-N 7-[6-(4-methylpiperazin-1-yl)indol-1-yl]sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2S(=O)(=O)C=3C=C4OCC(=O)NC4=CC=3)C2=C1 MYKIMDOOFLINFA-UHFFFAOYSA-N 0.000 claims description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
UCIATENKXUBJCF-UHFFFAOYSA-N [3-(6-piperazin-1-ylindazol-1-yl)sulfonylphenyl]-pyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)C(C=1)=CC=CC=1S(=O)(=O)N(C1=C2)N=CC1=CC=C2N1CCNCC1 UCIATENKXUBJCF-UHFFFAOYSA-N 0.000 claims description 2
BIUKPFYDYLHSNJ-UHFFFAOYSA-N [3-(6-piperazin-1-ylindol-1-yl)sulfonylphenyl]-pyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)C(C=1)=CC=CC=1S(=O)(=O)N(C1=C2)C=CC1=CC=C2N1CCNCC1 BIUKPFYDYLHSNJ-UHFFFAOYSA-N 0.000 claims description 2
MVXVYAKCVDQRLW-UHFFFAOYSA-N azain Natural products C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 2
125000005605 benzo group Chemical group 0.000 claims description 2
SUFHSRVCCZHSLN-UHFFFAOYSA-N ethyl 1-(benzenesulfonyl)-6-piperazin-1-ylindazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=CC=CC=3)C2=CC=1N1CCNCC1 SUFHSRVCCZHSLN-UHFFFAOYSA-N 0.000 claims description 2
GQJSETRXZMUTSY-UHFFFAOYSA-N ethyl 1-[(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)sulfonyl]-6-piperazin-1-ylindazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=C4OCCN(C)C4=CC=3)C2=CC=1N1CCNCC1 GQJSETRXZMUTSY-UHFFFAOYSA-N 0.000 claims description 2
PVPBTNNDIYRNOR-UHFFFAOYSA-N ethyl 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-(4-methylpiperazin-1-yl)indazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(CC3)OC)C2=CC=1N1CCN(C)CC1 PVPBTNNDIYRNOR-UHFFFAOYSA-N 0.000 claims description 2
ZTCBAMUXIBNHHY-UHFFFAOYSA-N ethyl 1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonyl-6-piperazin-1-ylindazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=C(C=CC=3)N3CC(CC3)OC)C2=CC=1N1CCNCC1 ZTCBAMUXIBNHHY-UHFFFAOYSA-N 0.000 claims description 2
239000010977 jade Substances 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
239000011574 phosphorus Substances 0.000 claims description 2
201000009032 substance abuse Diseases 0.000 claims description 2
125000003107 substituted aryl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
238000011321 prophylaxis Methods 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 1
231100000736 substance abuse Toxicity 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 276
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 406
239000000243 solution Substances 0.000 description 360
238000003756 stirring Methods 0.000 description 184
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 163
235000019439 ethyl acetate Nutrition 0.000 description 151
230000015572 biosynthetic process Effects 0.000 description 138
238000003786 synthesis reaction Methods 0.000 description 136
238000001704 evaporation Methods 0.000 description 111
230000008020 evaporation Effects 0.000 description 111
238000006243 chemical reaction Methods 0.000 description 110
238000004809 thin layer chromatography Methods 0.000 description 96
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
239000007787 solid Substances 0.000 description 87
238000001816 cooling Methods 0.000 description 81
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
238000001914 filtration Methods 0.000 description 70
239000003208 petroleum Substances 0.000 description 67
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
239000003921 oil Substances 0.000 description 66
239000002904 solvent Substances 0.000 description 56
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 55
239000011734 sodium Substances 0.000 description 55
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
239000004698 Polyethylene Substances 0.000 description 47
239000012044 organic layer Substances 0.000 description 45
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
239000000706 filtrate Substances 0.000 description 40
238000005481 NMR spectroscopy Methods 0.000 description 39
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 39
239000012298 atmosphere Substances 0.000 description 38
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
102000005962 receptors Human genes 0.000 description 36
108020003175 receptors Proteins 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
229910052757 nitrogen Inorganic materials 0.000 description 27
238000010926 purge Methods 0.000 description 27
239000003446 ligand Substances 0.000 description 25
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
239000012065 filter cake Substances 0.000 description 24
239000012267 brine Substances 0.000 description 23
230000000694 effects Effects 0.000 description 23
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-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
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 20
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
239000007788 liquid Substances 0.000 description 16
238000010992 reflux Methods 0.000 description 16
239000003795 chemical substances by application Substances 0.000 description 15
239000008177 pharmaceutical agent Substances 0.000 description 15
206010012289 Dementia Diseases 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 14
ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 14
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 13
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 12
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
208000020925 Bipolar disease Diseases 0.000 description 12
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 11
125000004356 hydroxy functional group Chemical group O* 0.000 description 11
239000000047 product Substances 0.000 description 11
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 10
206010008025 Cerebellar ataxia Diseases 0.000 description 10
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 10
235000019253 formic acid Nutrition 0.000 description 10
RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 10
229960001534 risperidone Drugs 0.000 description 10
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
230000027455 binding Effects 0.000 description 9
239000001257 hydrogen Substances 0.000 description 9
229910052744 lithium Inorganic materials 0.000 description 9
RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
0 CCCCIC(C)(CC1)C1NC1(C)C(C=CNC(C2)C3*2C3I)=C(*CC=CC)/C=C/C(C)(C)/C=C1 Chemical compound CCCCIC(C)(CC1)C1NC1(C)C(C=CNC(C2)C3*2C3I)=C(*CC=CC)/C=C/C(C)(C)/C=C1 0.000 description 8
229910004373 HOAc Inorganic materials 0.000 description 8
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 8
125000001072 heteroaryl group Chemical group 0.000 description 8
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
229910021591 Copper(I) chloride Inorganic materials 0.000 description 7
241000124008 Mammalia Species 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
238000003556 assay Methods 0.000 description 7
210000004227 basal ganglia Anatomy 0.000 description 7
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 7
239000012458 free base Substances 0.000 description 7
239000007789 gas Substances 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
201000006417 multiple sclerosis Diseases 0.000 description 7
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 7
VDQQJMHXZCMNMU-UHFFFAOYSA-N 1-phenylpyrrolidine Chemical compound C1CCCN1C1=CC=CC=C1 VDQQJMHXZCMNMU-UHFFFAOYSA-N 0.000 description 6
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 6
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 6
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
229940039856 aricept Drugs 0.000 description 6
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
125000001309 chloro group Chemical group Cl* 0.000 description 6
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
229960004132 diethyl ether Drugs 0.000 description 6
239000012467 final product Substances 0.000 description 6
229960003878 haloperidol Drugs 0.000 description 6
ZUFVXZVXEJHHBN-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroacridin-9-amine;chloride Chemical compound [Cl-].C1=CC=C2C([NH3+])=C(CCCC3)C3=NC2=C1 ZUFVXZVXEJHHBN-UHFFFAOYSA-N 0.000 description 6
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
125000002757 morpholinyl group Chemical group 0.000 description 6
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
229960001685 tacrine Drugs 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 5
POPPVIRYGJQIOF-UHFFFAOYSA-N 2-acetyloxyethyl(trimethyl)azanium;3-(1-methylpyrrolidin-2-yl)pyridine Chemical compound CC(=O)OCC[N+](C)(C)C.CN1CCCC1C1=CC=CN=C1 POPPVIRYGJQIOF-UHFFFAOYSA-N 0.000 description 5
QBWOYLOGZGLEAH-UHFFFAOYSA-N 6-bromo-1-[(4-methoxyphenyl)methyl]indazole Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(Br)=CC=C2C=N1 QBWOYLOGZGLEAH-UHFFFAOYSA-N 0.000 description 5
OWOHLURDBZHNGG-UHFFFAOYSA-N Hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)C2CCCN12 OWOHLURDBZHNGG-UHFFFAOYSA-N 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
JEHKKBHWRAXMCH-UHFFFAOYSA-M benzenesulfinate Chemical compound [O-]S(=O)C1=CC=CC=C1 JEHKKBHWRAXMCH-UHFFFAOYSA-M 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
229940079593 drug Drugs 0.000 description 5
229960004756 ethanol Drugs 0.000 description 5
238000009472 formulation Methods 0.000 description 5
229960002715 nicotine Drugs 0.000 description 5
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
208000020016 psychiatric disease Diseases 0.000 description 5
229940076279 serotonin Drugs 0.000 description 5
239000007858 starting material Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
239000000725 suspension Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
ONHPOXROAPYCGT-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-pyrido[1,2-a]pyrazine Chemical compound C1CNCC2CCCCN21 ONHPOXROAPYCGT-UHFFFAOYSA-N 0.000 description 4
RWPLKRGISDOAAG-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-4-amine Chemical compound NC1=CC=CC2=C1CCO2 RWPLKRGISDOAAG-UHFFFAOYSA-N 0.000 description 4
QADONEWUQWFYIM-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-4-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC2=C1CCO2 QADONEWUQWFYIM-UHFFFAOYSA-N 0.000 description 4
WMKDUJVLNZANRN-UHFFFAOYSA-N 6-bromo-1h-indazole Chemical compound BrC1=CC=C2C=NNC2=C1 WMKDUJVLNZANRN-UHFFFAOYSA-N 0.000 description 4
VWZLJQPIXFFAEV-UHFFFAOYSA-N 6-bromo-3-ethyl-1-[(4-methoxyphenyl)methyl]indazole Chemical compound C12=CC(Br)=CC=C2C(CC)=NN1CC1=CC=C(OC)C=C1 VWZLJQPIXFFAEV-UHFFFAOYSA-N 0.000 description 4
XZRBYJWQQQBHLP-UHFFFAOYSA-N 6-bromo-3-ethyl-2h-indazole Chemical compound C1=C(Br)C=CC2=C(CC)NN=C21 XZRBYJWQQQBHLP-UHFFFAOYSA-N 0.000 description 4
BTYCNIIIWYDUOF-UHFFFAOYSA-N 6-nitro-2,3-dihydro-1-benzofuran-5-amine Chemical compound C1=C([N+]([O-])=O)C(N)=CC2=C1OCC2 BTYCNIIIWYDUOF-UHFFFAOYSA-N 0.000 description 4
206010003694 Atrophy Diseases 0.000 description 4
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 4
208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 4
208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 4
241000282412 Homo Species 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
208000019430 Motor disease Diseases 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000000556 agonist Substances 0.000 description 4
230000003281 allosteric effect Effects 0.000 description 4
230000037444 atrophy Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 4
229960004170 clozapine Drugs 0.000 description 4
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 4
230000001149 cognitive effect Effects 0.000 description 4
125000004663 dialkyl amino group Chemical group 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
230000006870 function Effects 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
125000000714 pyrimidinyl group Chemical group 0.000 description 4
125000000719 pyrrolidinyl group Chemical group 0.000 description 4
125000000168 pyrrolyl group Chemical group 0.000 description 4
239000002287 radioligand Substances 0.000 description 4
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
229940039925 zyprexa Drugs 0.000 description 4
AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 3
GIJXKZJWITVLHI-YOFSQIOKSA-N (1R,5S)-3-(diphenylmethyl)oxy-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound C([C@H]1CC[C@@H](C2)N1C)C2OC(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-YOFSQIOKSA-N 0.000 description 3
TWHNMSJGYKMTRB-KXYUELECSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-methylphenol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 TWHNMSJGYKMTRB-KXYUELECSA-N 0.000 description 3
BWIJLTPDZWUMHT-UHFFFAOYSA-N (6-bromoindol-1-yl)-tri(propan-2-yl)silane Chemical class C1=C(Br)C=C2N([Si](C(C)C)(C(C)C)C(C)C)C=CC2=C1 BWIJLTPDZWUMHT-UHFFFAOYSA-N 0.000 description 3
RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 3
KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 3
JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical compound BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 3
SKCNYQBWULWGAP-UHFFFAOYSA-N 1-(3-bromophenyl)pyrrolidine Chemical compound BrC1=CC=CC(N2CCCC2)=C1 SKCNYQBWULWGAP-UHFFFAOYSA-N 0.000 description 3
BXUJZCANPAZYEJ-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-6-piperazin-1-ylindazole Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(N3CCNCC3)=CC=C2C=N1 BXUJZCANPAZYEJ-UHFFFAOYSA-N 0.000 description 3
RBYQYPQIZQKEFL-UHFFFAOYSA-N 1-methoxypyrrolidine Chemical compound CON1CCCC1 RBYQYPQIZQKEFL-UHFFFAOYSA-N 0.000 description 3
ZDLCRJZSWKJVQO-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-6-amine Chemical compound NC1=CC=C2CCOC2=C1 ZDLCRJZSWKJVQO-UHFFFAOYSA-N 0.000 description 3
UHYIBERPFLCTBR-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-6-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2CCOC2=C1 UHYIBERPFLCTBR-UHFFFAOYSA-N 0.000 description 3
ORIHZIZPTZTNCU-VMPITWQZSA-N 2-[(E)-hydroxyiminomethyl]phenol Chemical compound O\N=C\C1=CC=CC=C1O ORIHZIZPTZTNCU-VMPITWQZSA-N 0.000 description 3
IKNPRYWTPFSTAT-UHFFFAOYSA-N 2-benzyl-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine Chemical compound C1CN2CCCCC2CN1CC1=CC=CC=C1 IKNPRYWTPFSTAT-UHFFFAOYSA-N 0.000 description 3
PXAVAZKTFFJJEU-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinolin-8-amine Chemical compound C1=CC(N)=C2CN(C)CCC2=C1 PXAVAZKTFFJJEU-UHFFFAOYSA-N 0.000 description 3
YEYHIOACCQXLCJ-UHFFFAOYSA-N 2-oxo-1h-quinoline-6-sulfonyl chloride Chemical compound N1C(=O)C=CC2=CC(S(=O)(=O)Cl)=CC=C21 YEYHIOACCQXLCJ-UHFFFAOYSA-N 0.000 description 3
WAWDOEHEAULMGC-UHFFFAOYSA-N 3-[(6-butoxypyridin-3-yl)diazenyl]pyridine-2,6-diamine Chemical compound C1=NC(OCCCC)=CC=C1N=NC1=CC=C(N)N=C1N WAWDOEHEAULMGC-UHFFFAOYSA-N 0.000 description 3
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 3
BWRWNUQAQPAYCK-UHFFFAOYSA-N 3-methoxypyrrolidine Chemical compound COC1CCNC1 BWRWNUQAQPAYCK-UHFFFAOYSA-N 0.000 description 3
CDAWVCWDNKOVAE-UHFFFAOYSA-N 3-pyrrolidin-1-ylbenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC(N2CCCC2)=C1 CDAWVCWDNKOVAE-UHFFFAOYSA-N 0.000 description 3
KZVBBVPCVQEVQK-UHFFFAOYSA-N 4-(dimethylamino)benzenesulfonic acid Chemical compound CN(C)C1=CC=C(S(O)(=O)=O)C=C1 KZVBBVPCVQEVQK-UHFFFAOYSA-N 0.000 description 3
VGJCCTYTFGHTHN-UHFFFAOYSA-N 4-bromo-2-nitro-1-propylbenzene Chemical compound CCCC1=CC=C(Br)C=C1[N+]([O-])=O VGJCCTYTFGHTHN-UHFFFAOYSA-N 0.000 description 3
NIDJEJJNLYVSBK-UHFFFAOYSA-M 5-bromo-2-methyl-8-nitroisoquinolin-2-ium;iodide Chemical compound [I-].BrC1=CC=C([N+]([O-])=O)C2=C[N+](C)=CC=C21 NIDJEJJNLYVSBK-UHFFFAOYSA-M 0.000 description 3
RXQNKKRGJJRMKD-UHFFFAOYSA-N 5-bromo-2-methylaniline Chemical compound CC1=CC=C(Br)C=C1N RXQNKKRGJJRMKD-UHFFFAOYSA-N 0.000 description 3
ULGOLOXWHJEZNZ-UHFFFAOYSA-N 5-bromo-8-nitroisoquinoline Chemical compound C1=NC=C2C([N+](=O)[O-])=CC=C(Br)C2=C1 ULGOLOXWHJEZNZ-UHFFFAOYSA-N 0.000 description 3
CYJZJGYYTFQQBY-UHFFFAOYSA-N 5-bromoisoquinoline Chemical compound N1=CC=C2C(Br)=CC=CC2=C1 CYJZJGYYTFQQBY-UHFFFAOYSA-N 0.000 description 3
MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 3
ZIOGUNUUBPDESL-UHFFFAOYSA-N 6-nitro-2,3-dihydro-1-benzofuran Chemical compound [O-][N+](=O)C1=CC=C2CCOC2=C1 ZIOGUNUUBPDESL-UHFFFAOYSA-N 0.000 description 3
SAOSRZZZVNSGKU-UHFFFAOYSA-N 6-piperazin-1-yl-1h-indazole Chemical compound C1CNCCN1C1=CC=C(C=NN2)C2=C1 SAOSRZZZVNSGKU-UHFFFAOYSA-N 0.000 description 3
HEVSJNXWDZDGHL-UHFFFAOYSA-N 8-bromo-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC(Br)=C2CN(C)CCC2=C1 HEVSJNXWDZDGHL-UHFFFAOYSA-N 0.000 description 3
208000000044 Amnesia Diseases 0.000 description 3
XIQVNETUBQGFHX-UHFFFAOYSA-N Ditropan Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC#CCN(CC)CC)C1CCCCC1 XIQVNETUBQGFHX-UHFFFAOYSA-N 0.000 description 3
206010013654 Drug abuse Diseases 0.000 description 3
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 3
101000964051 Homo sapiens 5-hydroxytryptamine receptor 6 Proteins 0.000 description 3
108010005716 Interferon beta-1a Proteins 0.000 description 3
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 3
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
229930182821 L-proline Natural products 0.000 description 3
208000002569 Machado-Joseph Disease Diseases 0.000 description 3
208000026139 Memory disease Diseases 0.000 description 3
208000001089 Multiple system atrophy Diseases 0.000 description 3
PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 3
BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 3
206010033664 Panic attack Diseases 0.000 description 3
AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 3
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
125000002252 acyl group Chemical group 0.000 description 3
238000005273 aeration Methods 0.000 description 3
125000003282 alkyl amino group Chemical group 0.000 description 3
229960000836 amitriptyline Drugs 0.000 description 3
KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 3
229940003504 avonex Drugs 0.000 description 3
229960002170 azathioprine Drugs 0.000 description 3
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 3
229940049706 benzodiazepine Drugs 0.000 description 3
150000001557 benzodiazepines Chemical class 0.000 description 3
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000000872 buffer Substances 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229960003920 cocaine Drugs 0.000 description 3
230000019771 cognition Effects 0.000 description 3
229940076405 detrol Drugs 0.000 description 3
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000006196 drop Substances 0.000 description 3
239000000262 estrogen Substances 0.000 description 3
229940011871 estrogen Drugs 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
229960002464 fluoxetine Drugs 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
208000003906 hydrocephalus Diseases 0.000 description 3
239000005457 ice water Substances 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
229960004801 imipramine Drugs 0.000 description 3
BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 3
230000006872 improvement Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
229960004502 levodopa Drugs 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 3
238000004949 mass spectrometry Methods 0.000 description 3
230000006984 memory degeneration Effects 0.000 description 3
208000023060 memory loss Diseases 0.000 description 3
108020004999 messenger RNA Proteins 0.000 description 3
229960000485 methotrexate Drugs 0.000 description 3
XWXFZELDFAXOOL-UHFFFAOYSA-N methyl 1-(2-chloroacetyl)piperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1C(=O)CCl XWXFZELDFAXOOL-UHFFFAOYSA-N 0.000 description 3
APCHKWZTSCBBJX-UHFFFAOYSA-N methyl piperidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1CCCCN1 APCHKWZTSCBBJX-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
229940101972 mirapex Drugs 0.000 description 3
PJCRLXRVQIWOHM-UHFFFAOYSA-N n-(2,3-dihydro-1-benzofuran-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2OCCC2=C1 PJCRLXRVQIWOHM-UHFFFAOYSA-N 0.000 description 3
229940072228 neurontin Drugs 0.000 description 3
229960001158 nortriptyline Drugs 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
229940105606 oxycontin Drugs 0.000 description 3
208000019906 panic disease Diseases 0.000 description 3
229960002296 paroxetine Drugs 0.000 description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
UWCVGPLTGZWHGS-ZORIOUSZSA-N pergolide mesylate Chemical compound CS(O)(=O)=O.C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 UWCVGPLTGZWHGS-ZORIOUSZSA-N 0.000 description 3
229940088507 permax Drugs 0.000 description 3
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 3
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 3
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 3
229920000155 polyglutamine Polymers 0.000 description 3
108010040003 polyglutamine Proteins 0.000 description 3
239000000843 powder Substances 0.000 description 3
APVQOOKHDZVJEX-QTPLPEIMSA-N pramipexole hydrochloride Chemical compound O.Cl.Cl.C1[C@@H](NCCC)CCC2=C1SC(N)=N2 APVQOOKHDZVJEX-QTPLPEIMSA-N 0.000 description 3
229960002429 proline Drugs 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
125000003226 pyrazolyl group Chemical group 0.000 description 3
QPMSJEFZULFYTB-UHFFFAOYSA-N pyrrolidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CCNC1 QPMSJEFZULFYTB-UHFFFAOYSA-N 0.000 description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
238000000926 separation method Methods 0.000 description 3
VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 3
229960002073 sertraline Drugs 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
239000003826 tablet Substances 0.000 description 3
229940090016 tegretol Drugs 0.000 description 3
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 3
125000000335 thiazolyl group Chemical group 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
239000003643 water by type Substances 0.000 description 3
JLFONDOSQUZBGQ-NSHDSACASA-N (3s)-1-(4-bromophenyl)-3-methoxypyrrolidine Chemical compound C1[C@@H](OC)CCN1C1=CC=C(Br)C=C1 JLFONDOSQUZBGQ-NSHDSACASA-N 0.000 description 2
BWRWNUQAQPAYCK-YFKPBYRVSA-N (3s)-3-methoxypyrrolidine Chemical compound CO[C@H]1CCNC1 BWRWNUQAQPAYCK-YFKPBYRVSA-N 0.000 description 2
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
OPBSNAYKUYMJDO-UHFFFAOYSA-N 1,2,3,4,6,7-hexahydropyrrolo[1,2-a]pyrazine Chemical compound C1CNCC2=CCCN21 OPBSNAYKUYMJDO-UHFFFAOYSA-N 0.000 description 2
GFZNUBDWJHDOBY-UHFFFAOYSA-N 1,2-benzoxazole-5-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2ON=CC2=C1 GFZNUBDWJHDOBY-UHFFFAOYSA-N 0.000 description 2
GGANKCYHHSNNJR-UHFFFAOYSA-N 1,3-dibromo-2-(2-bromoethoxy)benzene Chemical compound BrCCOC1=C(Br)C=CC=C1Br GGANKCYHHSNNJR-UHFFFAOYSA-N 0.000 description 2
MMVUJVASBDVNGJ-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-5-yl)ethanone Chemical compound CC(=O)C1=CC=C2OCCC2=C1 MMVUJVASBDVNGJ-UHFFFAOYSA-N 0.000 description 2
BKCRWJVAWUTNEA-UHFFFAOYSA-N 1-(3-bromophenyl)-3-methoxypyrrolidine Chemical compound C1C(OC)CCN1C1=CC=CC(Br)=C1 BKCRWJVAWUTNEA-UHFFFAOYSA-N 0.000 description 2
BODNUSXUIHPKSR-UHFFFAOYSA-N 1-(6-bromo-3-ethylindazol-1-yl)ethanone Chemical compound BrC1=CC=C2C(CC)=NN(C(C)=O)C2=C1 BODNUSXUIHPKSR-UHFFFAOYSA-N 0.000 description 2
MMYFQBBNEVXKAO-UHFFFAOYSA-N 1-(6-bromoindazol-1-yl)ethanone Chemical compound C1=C(Br)C=C2N(C(=O)C)N=CC2=C1 MMYFQBBNEVXKAO-UHFFFAOYSA-N 0.000 description 2
MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 2
ZQEBQGAAWMOMAI-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC1C(O)=O ZQEBQGAAWMOMAI-UHFFFAOYSA-N 0.000 description 2
HWBWYCWMXURFEP-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methyl]-6-(4-methylpiperazin-1-yl)indazole Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(N3CCN(C)CC3)=CC=C2C=N1 HWBWYCWMXURFEP-UHFFFAOYSA-N 0.000 description 2
QNFXLCHANYHGIF-UHFFFAOYSA-N 1-acetyl-2,3-dihydroindole-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2N(C(=O)C)CCC2=C1 QNFXLCHANYHGIF-UHFFFAOYSA-N 0.000 description 2
CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 2
JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 2
QZVLTIYFENRBIK-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-pyrido[1,2-a]pyrazine;dihydrochloride Chemical compound Cl.Cl.C1CNCC2CCCCN21 QZVLTIYFENRBIK-UHFFFAOYSA-N 0.000 description 2
UNECAYDZDLGSLP-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-7-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC2=C1OCC2 UNECAYDZDLGSLP-UHFFFAOYSA-N 0.000 description 2
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
SSIZLKDLDKIHEV-UHFFFAOYSA-N 2,6-dibromophenol Chemical compound OC1=C(Br)C=CC=C1Br SSIZLKDLDKIHEV-UHFFFAOYSA-N 0.000 description 2
CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
KYXSVGVQGFPNRQ-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC=C2CN(C)CCC2=C1 KYXSVGVQGFPNRQ-UHFFFAOYSA-N 0.000 description 2
PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical class C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 2
YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 2
YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 2
NEDNODJSBGNBIL-UHFFFAOYSA-N 3-(3-methoxypyrrolidin-1-yl)benzenesulfonyl chloride Chemical compound C1C(OC)CCN1C1=CC=CC(S(Cl)(=O)=O)=C1 NEDNODJSBGNBIL-UHFFFAOYSA-N 0.000 description 2
JCZDMBKPCOKANB-UHFFFAOYSA-N 3-(oxan-2-yloxy)pyrrolidine Chemical compound C1NCCC1OC1OCCCC1 JCZDMBKPCOKANB-UHFFFAOYSA-N 0.000 description 2
ARYDUJTZEBZGOM-JTQLQIEISA-N 3-bromo-5-[(3s)-3-methoxypyrrolidin-1-yl]pyridine Chemical compound C1[C@@H](OC)CCN1C1=CN=CC(Br)=C1 ARYDUJTZEBZGOM-JTQLQIEISA-N 0.000 description 2
RXGIEONBBREXOK-UHFFFAOYSA-N 3-ethyl-1-[(4-methoxyphenyl)methyl]-6-(4-methylpiperazin-1-yl)indazole Chemical compound C12=CC(N3CCN(C)CC3)=CC=C2C(CC)=NN1CC1=CC=C(OC)C=C1 RXGIEONBBREXOK-UHFFFAOYSA-N 0.000 description 2
JYBCQSGFNBISQP-UHFFFAOYSA-N 3-ethyl-6-piperazin-1-yl-2h-indazole Chemical compound C=1C=C2C(CC)=NNC2=CC=1N1CCNCC1 JYBCQSGFNBISQP-UHFFFAOYSA-N 0.000 description 2
RTQAIFXZCMVBDT-UHFFFAOYSA-N 4-(dimethylamino)benzenesulfonyl chloride Chemical compound CN(C)C1=CC=C(S(Cl)(=O)=O)C=C1 RTQAIFXZCMVBDT-UHFFFAOYSA-N 0.000 description 2
YJRQBOOMJGYUPI-UHFFFAOYSA-N 4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=CC=C2N(C)CCOC2=C1 YJRQBOOMJGYUPI-UHFFFAOYSA-N 0.000 description 2
UCMDYZOTFPIAQZ-UHFFFAOYSA-N 4-pyrrolidin-1-ylbenzenesulfonic acid Chemical compound C1=CC(S(=O)(=O)O)=CC=C1N1CCCC1 UCMDYZOTFPIAQZ-UHFFFAOYSA-N 0.000 description 2
QRCGFTXRXYMJOS-UHFFFAOYSA-N 4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)COC2=C1 QRCGFTXRXYMJOS-UHFFFAOYSA-N 0.000 description 2
GXGYWLOHPYNWFE-UHFFFAOYSA-N 5-amino-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=C1C=CC=C2N GXGYWLOHPYNWFE-UHFFFAOYSA-N 0.000 description 2
DXRCGGKIRYSZQP-UHFFFAOYSA-N 5-bromo-2-methyl-8-nitro-3,4-dihydro-1h-isoquinoline Chemical compound C1=CC([N+]([O-])=O)=C2CN(C)CCC2=C1Br DXRCGGKIRYSZQP-UHFFFAOYSA-N 0.000 description 2
FJAWZBJMVMDKCZ-UHFFFAOYSA-N 5-bromo-2-propylaniline Chemical compound CCCC1=CC=C(Br)C=C1N FJAWZBJMVMDKCZ-UHFFFAOYSA-N 0.000 description 2
JKYYKVDWDUHMEO-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-1h-indazole Chemical compound C1CN(C)CCN1C1=CC=C(C=NN2)C2=C1 JKYYKVDWDUHMEO-UHFFFAOYSA-N 0.000 description 2
BXXSCBCILYHKRB-UHFFFAOYSA-N 6-amino-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=CC(N)=CC=C21 BXXSCBCILYHKRB-UHFFFAOYSA-N 0.000 description 2
KSQKSHQUEREEKM-UHFFFAOYSA-N 7-amino-3,4-dihydro-1h-quinolin-2-one Chemical compound C1CC(=O)NC2=CC(N)=CC=C21 KSQKSHQUEREEKM-UHFFFAOYSA-N 0.000 description 2
RUZXDTHZHJTTRO-UHFFFAOYSA-N 7-amino-4h-1,4-benzoxazin-3-one Chemical compound N1C(=O)COC2=CC(N)=CC=C21 RUZXDTHZHJTTRO-UHFFFAOYSA-N 0.000 description 2
ACJWMXHKIDYANL-UHFFFAOYSA-N 8-amino-4h-1,4-benzoxazin-3-one Chemical compound N1C(=O)COC2=C1C=CC=C2N ACJWMXHKIDYANL-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
102100032187 Androgen receptor Human genes 0.000 description 2
108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
102000007371 Ataxin-3 Human genes 0.000 description 2
241000271566 Aves Species 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
241000283707 Capra Species 0.000 description 2
206010008748 Chorea Diseases 0.000 description 2
JNFPMRKNYOQKNO-UHFFFAOYSA-N ClS(=O)(=O)C1=COCC=N1 Chemical compound ClS(=O)(=O)C1=COCC=N1 JNFPMRKNYOQKNO-UHFFFAOYSA-N 0.000 description 2
201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 description 2
208000020401 Depressive disease Diseases 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
208000012661 Dyskinesia Diseases 0.000 description 2
JAGZUIGGHGTFHO-UHFFFAOYSA-N Ethyl 3-phenylpropanoate Chemical compound CCOC(=O)CCC1=CC=CC=C1 JAGZUIGGHGTFHO-UHFFFAOYSA-N 0.000 description 2
241000282326 Felis catus Species 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
206010061216 Infarction Diseases 0.000 description 2
208000027747 Kennedy disease Diseases 0.000 description 2
229910010082 LiAlH Inorganic materials 0.000 description 2
208000019022 Mood disease Diseases 0.000 description 2
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
WECKJONDRAUFDD-ZDUSSCGKSA-N N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)N[C@@H]1C(CC2)CCN2C1 WECKJONDRAUFDD-ZDUSSCGKSA-N 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
241001494479 Pecora Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
229960004373 acetylcholine Drugs 0.000 description 2
230000009471 action Effects 0.000 description 2
239000013543 active substance Substances 0.000 description 2
230000002411 adverse Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
229940005529 antipsychotics Drugs 0.000 description 2
239000000074 antisense oligonucleotide Substances 0.000 description 2
238000012230 antisense oligonucleotides Methods 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
SLQOMUWXSXWWDR-UHFFFAOYSA-N benzyl 3-(oxan-2-yloxy)pyrrolidine-1-carboxylate Chemical compound C1CC(OC2OCCCC2)CN1C(=O)OCC1=CC=CC=C1 SLQOMUWXSXWWDR-UHFFFAOYSA-N 0.000 description 2
MBLJFGOKYTZKMH-UHFFFAOYSA-N benzyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound C1C(O)CCN1C(=O)OCC1=CC=CC=C1 MBLJFGOKYTZKMH-UHFFFAOYSA-N 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
208000012601 choreatic disease Diseases 0.000 description 2
239000006071 cream Substances 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
229940064790 dilantin Drugs 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
230000004064 dysfunction Effects 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
OJOISAKQKBYKBE-UHFFFAOYSA-N ethyl 3-(2,4-dinitrophenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O OJOISAKQKBYKBE-UHFFFAOYSA-N 0.000 description 2
229940108366 exelon Drugs 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
230000005714 functional activity Effects 0.000 description 2
208000020694 gallbladder disease Diseases 0.000 description 2
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
239000003193 general anesthetic agent Substances 0.000 description 2
235000004554 glutamine Nutrition 0.000 description 2
125000004446 heteroarylalkyl group Chemical group 0.000 description 2
210000001320 hippocampus Anatomy 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
125000005113 hydroxyalkoxy group Chemical group 0.000 description 2
125000002768 hydroxyalkyl group Chemical group 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000007574 infarction Effects 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 2
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
KGEUEOSVSQHDFF-UHFFFAOYSA-N isoquinoline-8-sulfonic acid Chemical compound C1=NC=CC2=CC=CC(=C12)S(=O)(=O)O KGEUEOSVSQHDFF-UHFFFAOYSA-N 0.000 description 2
125000000842 isoxazolyl group Chemical group 0.000 description 2
ABYJBTNDLPTCIZ-UHFFFAOYSA-M lithium;3-(3-methoxypyrrolidin-1-yl)benzenesulfinate Chemical compound [Li+].C1C(OC)CCN1C1=CC=CC(S([O-])=O)=C1 ABYJBTNDLPTCIZ-UHFFFAOYSA-M 0.000 description 2
WHAKPUUMBVXRFQ-UHFFFAOYSA-M lithium;3-pyrrolidin-1-ylbenzenesulfinate Chemical compound [Li+].[O-]S(=O)C1=CC=CC(N2CCCC2)=C1 WHAKPUUMBVXRFQ-UHFFFAOYSA-M 0.000 description 2
230000004807 localization Effects 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
208000027061 mild cognitive impairment Diseases 0.000 description 2
230000036651 mood Effects 0.000 description 2
230000035772 mutation Effects 0.000 description 2
DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 2
ICMIOUKQLCKMHC-UHFFFAOYSA-N n-(3-hydroxyphenyl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC(O)=C1 ICMIOUKQLCKMHC-UHFFFAOYSA-N 0.000 description 2
DAFHCFQPQMYDFI-UHFFFAOYSA-N n-(3-methoxyphenyl)-2,2-dimethylpropanamide Chemical compound COC1=CC=CC(NC(=O)C(C)(C)C)=C1 DAFHCFQPQMYDFI-UHFFFAOYSA-N 0.000 description 2
UEYUYGIOHOKHLF-UHFFFAOYSA-N n-(6-nitro-2,3-dihydro-1-benzofuran-5-yl)acetamide Chemical compound C1=C([N+]([O-])=O)C(NC(=O)C)=CC2=C1OCC2 UEYUYGIOHOKHLF-UHFFFAOYSA-N 0.000 description 2
VLQCFCOZILVCKP-UHFFFAOYSA-N n-[2-(2-hydroxyethyl)-3-methoxyphenyl]-2,2-dimethylpropanamide Chemical compound COC1=CC=CC(NC(=O)C(C)(C)C)=C1CCO VLQCFCOZILVCKP-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
210000001577 neostriatum Anatomy 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
235000005985 organic acids Nutrition 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
239000004031 partial agonist Substances 0.000 description 2
239000006072 paste Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
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 2
125000003386 piperidinyl group Chemical group 0.000 description 2
208000028173 post-traumatic stress disease Diseases 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
150000003235 pyrrolidines Chemical class 0.000 description 2
229960004431 quetiapine Drugs 0.000 description 2
URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical class C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000007921 spray Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
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 2
SVQJFCQAAKQKPJ-UHFFFAOYSA-N tert-butyl 2-[(2-ethoxy-2-oxoethyl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound CCOC(=O)CNC(=O)C1CCCN1C(=O)OC(C)(C)C SVQJFCQAAKQKPJ-UHFFFAOYSA-N 0.000 description 2
NMQPVLFAFAZYKC-UHFFFAOYSA-N tert-butyl 4-(1h-indol-6-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(C=CN2)C2=C1 NMQPVLFAFAZYKC-UHFFFAOYSA-N 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
150000003568 thioethers Chemical class 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
210000005166 vasculature Anatomy 0.000 description 2
238000010792 warming Methods 0.000 description 2
FBZWYFBNIGSUPS-UHFFFAOYSA-N (2-chlorophenyl) ethaneperoxoate Chemical compound CC(=O)OOC1=CC=CC=C1Cl FBZWYFBNIGSUPS-UHFFFAOYSA-N 0.000 description 1
TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
OCKIPDMKGPYYJS-ZDUSSCGKSA-N (3r)-spiro[1-azabicyclo[2.2.2]octane-3,2'-3h-furo[2,3-b]pyridine] Chemical compound C1N(CC2)CCC2[C@]21OC1=NC=CC=C1C2 OCKIPDMKGPYYJS-ZDUSSCGKSA-N 0.000 description 1
YNBXNVUZXFMNSJ-UHFFFAOYSA-N (4-bromophenyl) 1,4-diazabicyclo[3.2.2]nonane-4-carboxylate;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1OC(=O)N1C(CC2)CCN2CC1 YNBXNVUZXFMNSJ-UHFFFAOYSA-N 0.000 description 1
VOTYKHCJXKHHEQ-UHFFFAOYSA-N 1,2-benzoxazole-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2ON=CC2=C1 VOTYKHCJXKHHEQ-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
SWJPEBQEEAHIGZ-UHFFFAOYSA-N 1,4-dibromobenzene Chemical compound BrC1=CC=C(Br)C=C1 SWJPEBQEEAHIGZ-UHFFFAOYSA-N 0.000 description 1
RNTCWULFNYNFGI-UHFFFAOYSA-N 1-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CCC2=C1 RNTCWULFNYNFGI-UHFFFAOYSA-N 0.000 description 1
PZTXWIFWLHKDCW-UHFFFAOYSA-N 1-(3-bromophenyl)-3-(oxan-2-yloxy)pyrrolidine Chemical compound BrC1=CC=CC(N2CC(CC2)OC2OCCCC2)=C1 PZTXWIFWLHKDCW-UHFFFAOYSA-N 0.000 description 1
YQMXOIAIYXXXEE-UHFFFAOYSA-N 1-benzylpyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-UHFFFAOYSA-N 0.000 description 1
NUPWGLKBGVNSJX-UHFFFAOYSA-N 1-bromo-4-propylbenzene Chemical compound CCCC1=CC=C(Br)C=C1 NUPWGLKBGVNSJX-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
YNSMEKCMCCGBSN-UHFFFAOYSA-N 2-(1h-indol-6-yl)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine Chemical compound C1=C2C=CNC2=CC(N2CCN3CCCCC3C2)=C1 YNSMEKCMCCGBSN-UHFFFAOYSA-N 0.000 description 1
CCVJVOCHEMNQGA-UHFFFAOYSA-N 2-(1h-indol-6-yl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine Chemical compound C1=C2C=CNC2=CC(N2CC3CCCN3CC2)=C1 CCVJVOCHEMNQGA-UHFFFAOYSA-N 0.000 description 1
BAEHJGMFXACOKH-UHFFFAOYSA-N 2-[1-[3-(3-methoxypyrrolidin-1-yl)phenyl]sulfonylindol-6-yl]-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine Chemical compound C1C(OC)CCN1C1=CC=CC(S(=O)(=O)N2C3=CC(=CC=C3C=C2)N2CC3CCCCN3CC2)=C1 BAEHJGMFXACOKH-UHFFFAOYSA-N 0.000 description 1
KUCWUAFNGCMZDB-UHFFFAOYSA-N 2-amino-3-nitrophenol Chemical compound NC1=C(O)C=CC=C1[N+]([O-])=O KUCWUAFNGCMZDB-UHFFFAOYSA-N 0.000 description 1
MHAFRUMLQZZSIN-UHFFFAOYSA-N 2-amino-4-chloro-6-nitrophenol Chemical compound NC1=CC(Cl)=CC([N+]([O-])=O)=C1O MHAFRUMLQZZSIN-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
PGWOZBQWJLVIFX-UHFFFAOYSA-N 2-methyl-3,4-dihydro-1h-isoquinoline-8-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=C2CN(C)CCC2=C1 PGWOZBQWJLVIFX-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
AAXOGFHTBCUHOE-UHFFFAOYSA-N 2-oxo-3,4-dihydro-1h-quinoline-7-sulfonyl chloride Chemical compound C1CC(=O)NC2=CC(S(=O)(=O)Cl)=CC=C21 AAXOGFHTBCUHOE-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
WKURVXXDGMYSDP-UHFFFAOYSA-N 2-propyl-aniline Chemical compound CCCC1=CC=CC=C1N WKURVXXDGMYSDP-UHFFFAOYSA-N 0.000 description 1
CTFKJAAPCMUGML-UHFFFAOYSA-N 2h-1,4-benzoxazin-7-amine Chemical class N1=CCOC2=CC(N)=CC=C21 CTFKJAAPCMUGML-UHFFFAOYSA-N 0.000 description 1
TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 1
ZAFAVXITOVLGCJ-UHFFFAOYSA-N 3,4-dihydroquinolin-7-amine Chemical compound NC1=CC=C2CCC=NC2=C1 ZAFAVXITOVLGCJ-UHFFFAOYSA-N 0.000 description 1
SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 1
KZNBMKMFIGSQNV-UHFFFAOYSA-N 3-(dimethylamino)benzenesulfonyl chloride Chemical compound CN(C)C1=CC=CC(S(Cl)(=O)=O)=C1 KZNBMKMFIGSQNV-UHFFFAOYSA-N 0.000 description 1
MGVLYPOJXGBKCC-UHFFFAOYSA-N 3-[3-(oxan-2-yloxy)pyrrolidin-1-yl]benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC(N2CC(CC2)OC2OCCCC2)=C1 MGVLYPOJXGBKCC-UHFFFAOYSA-N 0.000 description 1
CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 1
229940018563 3-aminophenol Drugs 0.000 description 1
ZGIKWINFUGEQEO-UHFFFAOYSA-N 3-bromoquinoline Chemical compound C1=CC=CC2=CC(Br)=CN=C21 ZGIKWINFUGEQEO-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
GHIVCCHDGOFADS-UHFFFAOYSA-N 3-ethyl-1-[(4-methoxyphenyl)methyl]-6-piperazin-1-ylindazole Chemical compound C12=CC(N3CCNCC3)=CC=C2C(CC)=NN1CC1=CC=C(OC)C=C1 GHIVCCHDGOFADS-UHFFFAOYSA-N 0.000 description 1
FIEXCMCSAKGHNB-UHFFFAOYSA-N 3-ethyl-6-(4-methylpiperazin-1-yl)-2h-indazole Chemical compound C=1C=C2C(CC)=NNC2=CC=1N1CCN(C)CC1 FIEXCMCSAKGHNB-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
RWYAGUXUOGGNGN-UHFFFAOYSA-N 3-oxo-4h-1,4-benzoxazine-5-sulfonyl chloride Chemical compound O1CC(=O)NC2=C1C=CC=C2S(=O)(=O)Cl RWYAGUXUOGGNGN-UHFFFAOYSA-N 0.000 description 1
CGTCULUUVYBAPX-UHFFFAOYSA-N 3-oxo-4h-1,4-benzoxazine-6-sulfonyl chloride Chemical compound O1CC(=O)NC2=CC(S(=O)(=O)Cl)=CC=C21 CGTCULUUVYBAPX-UHFFFAOYSA-N 0.000 description 1
VKPIVQBWGKJCAB-UHFFFAOYSA-N 3-oxo-4h-1,4-benzoxazine-7-sulfonyl chloride Chemical compound N1C(=O)COC2=CC(S(=O)(=O)Cl)=CC=C21 VKPIVQBWGKJCAB-UHFFFAOYSA-N 0.000 description 1
GIQBGPOMMXZMRA-UHFFFAOYSA-N 3-oxo-4h-1,4-benzoxazine-8-sulfonyl chloride Chemical compound N1C(=O)COC2=C1C=CC=C2S(=O)(=O)Cl GIQBGPOMMXZMRA-UHFFFAOYSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
OUAVTZYGHGCCCB-UHFFFAOYSA-N 4-(2-oxopyrrolidin-1-yl)benzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1N1C(=O)CCC1 OUAVTZYGHGCCCB-UHFFFAOYSA-N 0.000 description 1
ORGVYMVAGRAZMH-JTQLQIEISA-N 4-[(3s)-3-methoxypyrrolidin-1-yl]benzenesulfonyl chloride Chemical compound C1[C@@H](OC)CCN1C1=CC=C(S(Cl)(=O)=O)C=C1 ORGVYMVAGRAZMH-JTQLQIEISA-N 0.000 description 1
KZNXALJXBRSMFL-UHFFFAOYSA-N 4-bromo-1-methyl-2-nitrobenzene Chemical compound CC1=CC=C(Br)C=C1[N+]([O-])=O KZNXALJXBRSMFL-UHFFFAOYSA-N 0.000 description 1
LHMOALYDXXCXLZ-UHFFFAOYSA-N 4-methyl-2,3-dihydro-1,4-benzoxazine-6-sulfonyl chloride Chemical compound C1=C(S(Cl)(=O)=O)C=C2N(C)CCOC2=C1 LHMOALYDXXCXLZ-UHFFFAOYSA-N 0.000 description 1
RUMNUSUMGZRQBF-UHFFFAOYSA-N 4-pyrrolidin-1-ylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1N1CCCC1 RUMNUSUMGZRQBF-UHFFFAOYSA-N 0.000 description 1
229940116892 5 Hydroxytryptamine 2B receptor antagonist Drugs 0.000 description 1
MVNKQGSBHALAEG-UHFFFAOYSA-N 5-(6-phenylpyridazin-3-yl)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole Chemical compound C1C2CNCC2CN1C(N=N1)=CC=C1C1=CC=CC=C1 MVNKQGSBHALAEG-UHFFFAOYSA-N 0.000 description 1
229940124801 5-HT6 antagonist Drugs 0.000 description 1
108091005436 5-HT7 receptors Proteins 0.000 description 1
DLUCMKOJJRGILC-VIFPVBQESA-N 5-[(3s)-3-methoxypyrrolidin-1-yl]pyridine-3-sulfonyl chloride Chemical compound C1[C@@H](OC)CCN1C1=CN=CC(S(Cl)(=O)=O)=C1 DLUCMKOJJRGILC-VIFPVBQESA-N 0.000 description 1
SWNSJLBQDHUEJV-BEFAXECRSA-N 5-[5-[(1r,5r)-6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl]pyridin-2-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CC=C(C=N2)N2C[C@H]3CN([C@H]3C2)C)=C1 SWNSJLBQDHUEJV-BEFAXECRSA-N 0.000 description 1
LUKNJAQKVPBDSC-SFHVURJKSA-N 5-[6-[[(3r)-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CC=C(N=N2)O[C@@H]2C3CCN(C2)CC3)=C1 LUKNJAQKVPBDSC-SFHVURJKSA-N 0.000 description 1
LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical class OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
102100027499 5-hydroxytryptamine receptor 1B Human genes 0.000 description 1
102100027493 5-hydroxytryptamine receptor 1D Human genes 0.000 description 1
102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
102100024956 5-hydroxytryptamine receptor 2B Human genes 0.000 description 1
102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 1
102100040370 5-hydroxytryptamine receptor 5A Human genes 0.000 description 1
MJMKRYIJNBIITM-UHFFFAOYSA-N 5-nitro-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=C1C=CC=C2[N+](=O)[O-] MJMKRYIJNBIITM-UHFFFAOYSA-N 0.000 description 1
WPHNRWNLNOQNQS-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-1h-indole Chemical compound C1CN(C)CCN1C1=CC=C(C=CN2)C2=C1 WPHNRWNLNOQNQS-UHFFFAOYSA-N 0.000 description 1
OYLJUJGLDPDXHP-UHFFFAOYSA-N 6-nitro-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=CC([N+](=O)[O-])=CC=C21 OYLJUJGLDPDXHP-UHFFFAOYSA-N 0.000 description 1
NKLKZGHSVVOPHC-UHFFFAOYSA-N 7-[6-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl)indol-1-yl]sulfonyl-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1CN2CCCCC2CN1C(C=C12)=CC=C2C=CN1S(=O)(=O)C1=CC=C2N(C)CCOC2=C1 NKLKZGHSVVOPHC-UHFFFAOYSA-N 0.000 description 1
YVGHCFMAEHXPBH-UHFFFAOYSA-N 7-nitro-4h-1,4-benzoxazin-3-one Chemical compound N1C(=O)COC2=CC([N+](=O)[O-])=CC=C21 YVGHCFMAEHXPBH-UHFFFAOYSA-N 0.000 description 1
LFQDPHSIICCBLE-UHFFFAOYSA-N 8-amino-6-chloro-4h-1,4-benzoxazin-3-one Chemical compound N1C(=O)COC2=C1C=C(Cl)C=C2N LFQDPHSIICCBLE-UHFFFAOYSA-N 0.000 description 1
102000009346 Adenosine receptors Human genes 0.000 description 1
108050000203 Adenosine receptors Proteins 0.000 description 1
206010001605 Alcohol poisoning Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
102000007372 Ataxin-1 Human genes 0.000 description 1
108010032963 Ataxin-1 Proteins 0.000 description 1
108010032947 Ataxin-3 Proteins 0.000 description 1
102100021321 Ataxin-3 Human genes 0.000 description 1
102000007368 Ataxin-7 Human genes 0.000 description 1
108010032953 Ataxin-7 Proteins 0.000 description 1
102000007370 Ataxin2 Human genes 0.000 description 1
108010032951 Ataxin2 Proteins 0.000 description 1
229930003347 Atropine Natural products 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 1
206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
ATZWXDWXCISHBE-UHFFFAOYSA-N CN1CC(CCC2)N2CC1 Chemical compound CN1CC(CCC2)N2CC1 ATZWXDWXCISHBE-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
108090000312 Calcium Channels Proteins 0.000 description 1
102000003922 Calcium Channels Human genes 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
208000020446 Cardiac disease Diseases 0.000 description 1
239000004381 Choline salt Substances 0.000 description 1
108010009685 Cholinergic Receptors Proteins 0.000 description 1
235000001258 Cinchona calisaya Nutrition 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
102000012437 Copper-Transporting ATPases Human genes 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
RPYWXZCFYPVCNQ-RVDMUPIBSA-N DMXB-A Chemical compound COC1=CC(OC)=CC=C1\C=C/1C(C=2C=NC=CC=2)=NCCC\1 RPYWXZCFYPVCNQ-RVDMUPIBSA-N 0.000 description 1
206010012239 Delusion Diseases 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
201000010374 Down Syndrome Diseases 0.000 description 1
206010014666 Endocarditis bacterial Diseases 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241000283086 Equidae Species 0.000 description 1
KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 1
206010063006 Facial spasm Diseases 0.000 description 1
206010016880 Folate deficiency Diseases 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
101150015707 HTR1A gene Proteins 0.000 description 1
101150050738 HTR1B gene Proteins 0.000 description 1
101150104779 HTR2A gene Proteins 0.000 description 1
101150049624 HTR5A gene Proteins 0.000 description 1
208000004547 Hallucinations Diseases 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
101150013372 Htr2c gene Proteins 0.000 description 1
RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
102000016193 Metabotropic glutamate receptors Human genes 0.000 description 1
108010010914 Metabotropic glutamate receptors Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
102000008300 Mutant Proteins Human genes 0.000 description 1
108010021466 Mutant Proteins Proteins 0.000 description 1
206010061533 Myotonia Diseases 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
102000016979 Other receptors Human genes 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
241000286209 Phasianidae Species 0.000 description 1
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241001282135 Poromitra oscitans Species 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000002667 Subdural Hematoma Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
206010042674 Swelling Diseases 0.000 description 1
101100321769 Takifugu rubripes htr1d gene Proteins 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
241000534944 Thia Species 0.000 description 1
208000030886 Traumatic Brain injury Diseases 0.000 description 1
241000209140 Triticum Species 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
229930003779 Vitamin B12 Natural products 0.000 description 1
208000018839 Wilson disease Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
206010048232 Yawning Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
STDQUFHBZPJVGP-UHFFFAOYSA-N [6-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl)indol-1-yl]-tri(propan-2-yl)silane Chemical compound C1CN2CCCCC2CN1C1=CC=C2C=CN([Si](C(C)C)(C(C)C)C(C)C)C2=C1 STDQUFHBZPJVGP-UHFFFAOYSA-N 0.000 description 1
DNFMDWAGFFWUGF-UHFFFAOYSA-N [6-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)indol-1-yl]-tri(propan-2-yl)silane Chemical compound C1CN2CCCC2CN1C1=CC=C2C=CN([Si](C(C)C)(C(C)C)C(C)C)C2=C1 DNFMDWAGFFWUGF-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
102000034337 acetylcholine receptors Human genes 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
230000036982 action potential Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
230000032683 aging Effects 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
108010080146 androgen receptors Proteins 0.000 description 1
229940035674 anesthetics Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
229960000396 atropine Drugs 0.000 description 1
239000003693 atypical antipsychotic agent Substances 0.000 description 1
229940127236 atypical antipsychotics Drugs 0.000 description 1
125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
208000009361 bacterial endocarditis Diseases 0.000 description 1
230000006399 behavior Effects 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
BOWAGQQKLAEDCZ-UHFFFAOYSA-N benzyl 1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine-2-carboxylate Chemical compound C1CN2CCCCC2CN1C(=O)OCC1=CC=CC=C1 BOWAGQQKLAEDCZ-UHFFFAOYSA-N 0.000 description 1
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
150000005347 biaryls Chemical class 0.000 description 1
210000000013 bile duct Anatomy 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
125000006267 biphenyl group Chemical group 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
208000034158 bleeding Diseases 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
OXKRFEWMSWPKKV-RXVVDRJESA-N bradanicline Chemical compound C([C@@H]1N2CCC(CC2)[C@@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-RXVVDRJESA-N 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
150000004648 butanoic acid derivatives Chemical class 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000000480 calcium channel blocker Substances 0.000 description 1
229930003827 cannabinoid Natural products 0.000 description 1
239000003557 cannabinoid Substances 0.000 description 1
239000007894 caplet Substances 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
206010008129 cerebral palsy Diseases 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
230000001055 chewing effect Effects 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
235000019417 choline salt Nutrition 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
KBEBGUQPQBELIU-UHFFFAOYSA-N cinnamic acid ethyl ester Natural products CCOC(=O)C=CC1=CC=CC=C1 KBEBGUQPQBELIU-UHFFFAOYSA-N 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000007278 cognition impairment Effects 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
238000012937 correction Methods 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
230000006378 damage Effects 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
231100000868 delusion Toxicity 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000000586 desensitisation Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 description 1
125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
229960003530 donepezil Drugs 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
238000009509 drug development Methods 0.000 description 1
238000007876 drug discovery Methods 0.000 description 1
230000036267 drug metabolism Effects 0.000 description 1
210000005069 ears Anatomy 0.000 description 1
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000003821 enantio-separation Methods 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
QJEKXRQMSHRIAP-UHFFFAOYSA-N ethyl 1-[(4-methyl-2,3-dihydro-1,4-benzoxazin-7-yl)sulfonyl]-6-(4-methylpiperazin-1-yl)indazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NN(S(=O)(=O)C=3C=C4OCCN(C)C4=CC=3)C2=CC=1N1CCN(C)CC1 QJEKXRQMSHRIAP-UHFFFAOYSA-N 0.000 description 1
UKAISZFWIBSMTB-UHFFFAOYSA-N ethyl 6-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-1h-indazole-3-carboxylate Chemical compound C=1C=C2C(C(=O)OCC)=NNC2=CC=1N1CCN(C(=O)OC(C)(C)C)CC1 UKAISZFWIBSMTB-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
LJJVZJSGXHJIPP-UHFFFAOYSA-N ethylpentyl Chemical group [CH2+]CCC[CH]C[CH2-] LJJVZJSGXHJIPP-UHFFFAOYSA-N 0.000 description 1
230000003090 exacerbative effect Effects 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
210000001652 frontal lobe Anatomy 0.000 description 1
ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical group O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 1
239000007897 gelcap Substances 0.000 description 1
229940005494 general anesthetics Drugs 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
150000002309 glutamines Chemical class 0.000 description 1
239000008187 granular material Substances 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004404 heteroalkyl group Chemical group 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 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
101150075901 htr2 gene Proteins 0.000 description 1
150000004678 hydrides Chemical group 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
230000002267 hypothalamic effect Effects 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
201000007119 infective endocarditis Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
GUSYANXQYUJOBH-UHFFFAOYSA-N isoquinolin-8-amine Chemical compound C1=NC=C2C(N)=CC=CC2=C1 GUSYANXQYUJOBH-UHFFFAOYSA-N 0.000 description 1
UYZLXCOQEDYFRO-UHFFFAOYSA-N isoquinoline-8-sulfonyl chloride Chemical compound C1=NC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 UYZLXCOQEDYFRO-UHFFFAOYSA-N 0.000 description 1
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
210000004558 lewy body Anatomy 0.000 description 1
239000000865 liniment Substances 0.000 description 1
229940040145 liniment Drugs 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
244000144972 livestock Species 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
210000001370 mediastinum Anatomy 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000007074 memory dysfunction Effects 0.000 description 1
230000006386 memory function Effects 0.000 description 1
230000003340 mental effect Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
210000002161 motor neuron Anatomy 0.000 description 1
239000003149 muscarinic antagonist Substances 0.000 description 1
230000003551 muscarinic effect Effects 0.000 description 1
CMRLNEYJEPELSM-BTQNPOSSSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1h-indazole-3-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C(N[C@H]3C4CCN(CC4)C3)=O)=NNC2=C1 CMRLNEYJEPELSM-BTQNPOSSSA-N 0.000 description 1
RAEPYEDOZKENTI-UHFFFAOYSA-N n-[1-(2,3-dihydro-1-benzofuran-5-yl)ethylidene]hydroxylamine Chemical compound ON=C(C)C1=CC=C2OCCC2=C1 RAEPYEDOZKENTI-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
230000000626 neurodegenerative effect Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000001009 nucleus accumben Anatomy 0.000 description 1
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 description 1
239000002674 ointment Substances 0.000 description 1
210000000287 oocyte Anatomy 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
208000021090 palsy Diseases 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
230000008447 perception Effects 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
208000022821 personality disease Diseases 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase 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
XAMUDJHXFNRLCY-UHFFFAOYSA-N phenthoate Chemical compound CCOC(=O)C(SP(=S)(OC)OC)C1=CC=CC=C1 XAMUDJHXFNRLCY-UHFFFAOYSA-N 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000005547 pivalate group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
DVECLMOWYVDJRM-UHFFFAOYSA-M pyridine-3-sulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CN=C1 DVECLMOWYVDJRM-UHFFFAOYSA-M 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
229960000948 quinine Drugs 0.000 description 1
ITXXHPLNLYEVQT-UHFFFAOYSA-N quinoline-3-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CN=C21 ITXXHPLNLYEVQT-UHFFFAOYSA-N 0.000 description 1
VSAXLHSQUHPTCS-UHFFFAOYSA-N quinoline-3-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CN=C21 VSAXLHSQUHPTCS-UHFFFAOYSA-N 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000012216 screening Methods 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000003751 serotonin 6 antagonist Substances 0.000 description 1
239000000779 smoke Substances 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
LZCVVMQABORALM-UHFFFAOYSA-N spiro[2.5]octyl Chemical group [CH]1CC11CCCCC1 LZCVVMQABORALM-UHFFFAOYSA-N 0.000 description 1
GAJDDVONBAWAGB-UHFFFAOYSA-N spiro[2.6]nonyl Chemical group [CH]1CC11CCCCCC1 GAJDDVONBAWAGB-UHFFFAOYSA-N 0.000 description 1
LMUMMJCCZMWLEN-UHFFFAOYSA-N spiro[3.3]heptyl Chemical group [CH]1CCC11CCC1 LMUMMJCCZMWLEN-UHFFFAOYSA-N 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
150000003444 succinic acids Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000004808 supercritical fluid chromatography Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
APCBTRDHCDOPNY-UHFFFAOYSA-N tert-butyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)C1 APCBTRDHCDOPNY-UHFFFAOYSA-N 0.000 description 1
HYKLCBVCBVKEDJ-UHFFFAOYSA-N tert-butyl 4-(1h-indazol-6-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(C=NN2)C2=C1 HYKLCBVCBVKEDJ-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
150000003530 tetrahydroquinolines Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
150000003567 thiocyanates Chemical class 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
230000009529 traumatic brain injury Effects 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
235000019163 vitamin B12 Nutrition 0.000 description 1
239000011715 vitamin B12 Substances 0.000 description 1
208000002670 vitamin B12 deficiency Diseases 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1