CA2837247C - 1 , 2 , 4 -thiadiazol- 5 -ylpiperazine derivatives useful in the treatment neurodegenerative diseases - Google Patents

Info

Publication number

CA2837247C

CA2837247C CA2837247A CA2837247A CA2837247C CA 2837247 C CA2837247 C CA 2837247C CA 2837247 A CA2837247 A CA 2837247A CA 2837247 A CA2837247 A CA 2837247A CA 2837247 C CA2837247 C CA 2837247C

Authority

CA

Canada

Prior art keywords

thiadiazol

phenyl

piperazine

chloro

ethyl

Prior art date

2011-07-01

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

Active

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000011282 treatment Methods 0.000 title claims description 17
• 208000015122 neurodegenerative disease Diseases 0.000 title abstract description 4
• 230000004770 neurodegeneration Effects 0.000 title description 5
• BLGDMQAEKJZPMD-UHFFFAOYSA-N 5-piperazin-1-yl-1,2,4-thiadiazole Chemical class C1CNCCN1C1=NC=NS1 BLGDMQAEKJZPMD-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 377
• 238000000034 method Methods 0.000 claims description 203
• 229910052736 halogen Inorganic materials 0.000 claims description 79
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
• 150000002367 halogens Chemical group 0.000 claims description 73
• -1 pyridine-2-yl Chemical group 0.000 claims description 70
• 125000000217 alkyl group Chemical group 0.000 claims description 47
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 37
• 239000001257 hydrogen Substances 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
• 239000000203 mixture Substances 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
• 208000024827 Alzheimer disease Diseases 0.000 claims description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
• 201000010099 disease Diseases 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 15
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 15
• 206010034010 Parkinsonism Diseases 0.000 claims description 15
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 15
• 210000000349 chromosome Anatomy 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 15
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 14
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 14
• 125000006239 protecting group Chemical group 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• 239000002253 acid Substances 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 6
• 238000010168 coupling process Methods 0.000 claims description 5
• 238000005859 coupling reaction Methods 0.000 claims description 5
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 4
• 230000008878 coupling Effects 0.000 claims description 4
• 239000013543 active substance Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 229920006395 saturated elastomer Polymers 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 6
• BUZINUAEKIOJLY-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(3-fluorophenyl)ethanol Chemical compound C=1C=CC(F)=CC=1C(O)CN(CC1)CCN1C(SN=1)=NC=1C1=CC=C(Cl)C=C1 BUZINUAEKIOJLY-UHFFFAOYSA-N 0.000 claims 1
• XRFAIYWPIAUAHX-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(3-fluorophenyl)ethanone Chemical compound FC1=CC=CC(C(=O)CN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 XRFAIYWPIAUAHX-UHFFFAOYSA-N 0.000 claims 1
• FBZFHISPFSGMND-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(3-methoxyphenyl)ethanol Chemical compound COC1=CC=CC(C(O)CN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 FBZFHISPFSGMND-UHFFFAOYSA-N 0.000 claims 1
• QTWOOFIWSNWWKJ-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(=O)CN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 QTWOOFIWSNWWKJ-UHFFFAOYSA-N 0.000 claims 1
• VGZKFJFOCJJUIX-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(4-methoxyphenyl)ethanol Chemical compound C1=CC(OC)=CC=C1C(O)CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 VGZKFJFOCJJUIX-UHFFFAOYSA-N 0.000 claims 1
• KWLYBUGBQINXJF-UHFFFAOYSA-N 2-[4-[3-(4-chlorophenyl)-1,2,4-thiadiazol-5-yl]piperazin-1-yl]-1-(4-methoxyphenyl)ethanone Chemical compound C1=CC(OC)=CC=C1C(=O)CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 KWLYBUGBQINXJF-UHFFFAOYSA-N 0.000 claims 1
• JDTBRDYDMPJKPM-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C(=CC=CC=2)Cl)=C1 JDTBRDYDMPJKPM-UHFFFAOYSA-N 0.000 claims 1
• GBMADOGXCFEIIV-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C(=CC=CC=2)Cl)CC1 GBMADOGXCFEIIV-UHFFFAOYSA-N 0.000 claims 1
• KGKMGJYUYLSDED-UHFFFAOYSA-N 3-(2-chloropyridin-4-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(Cl)=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 KGKMGJYUYLSDED-UHFFFAOYSA-N 0.000 claims 1
• PJEVWPQBNAPQLH-UHFFFAOYSA-N 3-(2-chloropyridin-4-yl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)N=CC=2)=C1 PJEVWPQBNAPQLH-UHFFFAOYSA-N 0.000 claims 1
• QBRAGJHSFRFKHO-UHFFFAOYSA-N 3-(2-methoxyphenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C(=CC=CC=2)OC)=C1 QBRAGJHSFRFKHO-UHFFFAOYSA-N 0.000 claims 1
• WHTZJCDHEGMKKJ-UHFFFAOYSA-N 3-(2-methoxyphenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C(=CC=CC=2)OC)CC1 WHTZJCDHEGMKKJ-UHFFFAOYSA-N 0.000 claims 1
• PVAKEJAPYADUTP-UHFFFAOYSA-N 3-(2-methylpyridin-4-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 PVAKEJAPYADUTP-UHFFFAOYSA-N 0.000 claims 1
• NMLHBVXOTXYTAN-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(C)=NC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 NMLHBVXOTXYTAN-UHFFFAOYSA-N 0.000 claims 1
• XQGPNJWUCITKNY-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 XQGPNJWUCITKNY-UHFFFAOYSA-N 0.000 claims 1
• UDOAVTLWFFMQSQ-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)CC1 UDOAVTLWFFMQSQ-UHFFFAOYSA-N 0.000 claims 1
• MEVIHYMBOSCWRY-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)=C1 MEVIHYMBOSCWRY-UHFFFAOYSA-N 0.000 claims 1
• DXCAQHRNCZNJLF-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)CC1 DXCAQHRNCZNJLF-UHFFFAOYSA-N 0.000 claims 1
• IQAHSIFLHRAGHO-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)CC1 IQAHSIFLHRAGHO-UHFFFAOYSA-N 0.000 claims 1
• HQGQUNSFWGWBFG-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)CC1 HQGQUNSFWGWBFG-UHFFFAOYSA-N 0.000 claims 1
• QGGSSHHYAIEOPB-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C(F)=CC=2)CC1 QGGSSHHYAIEOPB-UHFFFAOYSA-N 0.000 claims 1
• PJBUVAILLZFVSC-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-(oxan-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1C1=NSC(N2CCN(CCC3CCOCC3)CC2)=N1 PJBUVAILLZFVSC-UHFFFAOYSA-N 0.000 claims 1
• FBOMOPFUJVVGLJ-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-5-[4-[2-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1C1=NSC(N2CCN(CCC=3C=CC(=CC=3)C(F)(F)F)CC2)=N1 FBOMOPFUJVVGLJ-UHFFFAOYSA-N 0.000 claims 1
• GTDIKKYDJJCBOU-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=C(Cl)C=2)=C1 GTDIKKYDJJCBOU-UHFFFAOYSA-N 0.000 claims 1
• WDPKARWBEZBPSL-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=C(Cl)C=2)CC1 WDPKARWBEZBPSL-UHFFFAOYSA-N 0.000 claims 1
• JCQZXBDKYIJNHH-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-(2-cyclohexylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC3CCCCC3)CC2)=C1 JCQZXBDKYIJNHH-UHFFFAOYSA-N 0.000 claims 1
• YFGOGVZPRGTQKX-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 YFGOGVZPRGTQKX-UHFFFAOYSA-N 0.000 claims 1
• SWABBKDFIMWQPL-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 SWABBKDFIMWQPL-UHFFFAOYSA-N 0.000 claims 1
• CWDIRRHPNNIIPG-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)=C1 CWDIRRHPNNIIPG-UHFFFAOYSA-N 0.000 claims 1
• KXKYRFCNEGQGEJ-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 KXKYRFCNEGQGEJ-UHFFFAOYSA-N 0.000 claims 1
• PWBSJUJINZLOQZ-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)=C1 PWBSJUJINZLOQZ-UHFFFAOYSA-N 0.000 claims 1
• GZFZJFAULLFBSN-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 GZFZJFAULLFBSN-UHFFFAOYSA-N 0.000 claims 1
• ZCSNLYSNHLTVIG-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 ZCSNLYSNHLTVIG-UHFFFAOYSA-N 0.000 claims 1
• KZCOVBGYOSSNIR-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 KZCOVBGYOSSNIR-UHFFFAOYSA-N 0.000 claims 1
• UCNVLKZZTGOBHP-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-(oxan-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC3CCOCC3)CC2)=C1 UCNVLKZZTGOBHP-UHFFFAOYSA-N 0.000 claims 1
• KGHSOOQKQYDWIJ-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)=C1 KGHSOOQKQYDWIJ-UHFFFAOYSA-N 0.000 claims 1
• AVJPWYVUZUBHEE-UHFFFAOYSA-N 3-(3-chlorophenyl)-5-[4-[2-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=CC=2)CC1 AVJPWYVUZUBHEE-UHFFFAOYSA-N 0.000 claims 1
• YAOITOZQMCXAOW-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 YAOITOZQMCXAOW-UHFFFAOYSA-N 0.000 claims 1
• IIEMDTMHNFFJMH-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=C(F)C=CC=2)CC1 IIEMDTMHNFFJMH-UHFFFAOYSA-N 0.000 claims 1
• OCDPBSABQZWGGD-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C=CC=2)CC1 OCDPBSABQZWGGD-UHFFFAOYSA-N 0.000 claims 1
• AJWMTDGJRXOHRL-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C=CC=2)CC1 AJWMTDGJRXOHRL-UHFFFAOYSA-N 0.000 claims 1
• ITPFHDUQVFOQMJ-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(F)C=CC=2)CC1 ITPFHDUQVFOQMJ-UHFFFAOYSA-N 0.000 claims 1
• AZMBIGKRFHDKPD-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=C(C=CC=3)C(F)(F)F)CC2)=C1 AZMBIGKRFHDKPD-UHFFFAOYSA-N 0.000 claims 1
• TUTWBLQEVFSBGT-UHFFFAOYSA-N 3-(3-methoxyphenyl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(C=2N=C(SN=2)N2CCN(CC=3C(=CC=CC=3)C)CC2)=C1 TUTWBLQEVFSBGT-UHFFFAOYSA-N 0.000 claims 1
• ZYKSCGMOAHKGGS-UHFFFAOYSA-N 3-(3-methoxyphenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(OC)C=CC=2)=C1 ZYKSCGMOAHKGGS-UHFFFAOYSA-N 0.000 claims 1
• LRCJCHSKPNFERC-UHFFFAOYSA-N 3-(3-methoxyphenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(OC)C=CC=2)CC1 LRCJCHSKPNFERC-UHFFFAOYSA-N 0.000 claims 1
• GTQQTIMKLKEAAX-UHFFFAOYSA-N 3-(4-chloro-2-fluorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C(=CC(Cl)=CC=2)F)=C1 GTQQTIMKLKEAAX-UHFFFAOYSA-N 0.000 claims 1
• NDDSZUMBYIURDY-UHFFFAOYSA-N 3-(4-chloro-2-fluorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C(=CC(Cl)=CC=2)F)CC1 NDDSZUMBYIURDY-UHFFFAOYSA-N 0.000 claims 1
• KLVOUSNRWZLUBQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-(2-cyclohexylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1C1=NSC(N2CCN(CCC3CCCCC3)CC2)=N1 KLVOUSNRWZLUBQ-UHFFFAOYSA-N 0.000 claims 1
• WRAAQLMOMLDEIQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 WRAAQLMOMLDEIQ-UHFFFAOYSA-N 0.000 claims 1
• VTVWVMSUUALLKR-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[1-(4-methoxyphenyl)propan-2-yl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CC(C)N1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 VTVWVMSUUALLKR-UHFFFAOYSA-N 0.000 claims 1
• YWJORACHBFMAHI-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(2-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1C1=NSC(N2CCN(CCC=3C(=CC=CC=3)Cl)CC2)=N1 YWJORACHBFMAHI-UHFFFAOYSA-N 0.000 claims 1
• IGTBWCADUNEGNF-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(2-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC1=CC=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 IGTBWCADUNEGNF-UHFFFAOYSA-N 0.000 claims 1
• FKQXPZJZEYMZCV-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(2-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 FKQXPZJZEYMZCV-UHFFFAOYSA-N 0.000 claims 1
• XYOAMMWCXYDWLM-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 XYOAMMWCXYDWLM-UHFFFAOYSA-N 0.000 claims 1
• QMKHWILIGUZMOI-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 QMKHWILIGUZMOI-UHFFFAOYSA-N 0.000 claims 1
• HFNVJMXBTBQXGN-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1C1=NSC(N2CCN(CCC=3C=C(Cl)C=CC=3)CC2)=N1 HFNVJMXBTBQXGN-UHFFFAOYSA-N 0.000 claims 1
• LXLUZCUMXAFCFD-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-fluoro-4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 LXLUZCUMXAFCFD-UHFFFAOYSA-N 0.000 claims 1
• RBTMNRQUYHEQKC-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 RBTMNRQUYHEQKC-UHFFFAOYSA-N 0.000 claims 1
• MLGQQDFJZPZVAE-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 MLGQQDFJZPZVAE-UHFFFAOYSA-N 0.000 claims 1
• UYJAHJRAHMULBN-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-methylphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 UYJAHJRAHMULBN-UHFFFAOYSA-N 0.000 claims 1
• GHLMRZAWSZSDLJ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(3-propan-2-yloxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC(C)OC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 GHLMRZAWSZSDLJ-UHFFFAOYSA-N 0.000 claims 1
• VMNMAOFYRIIATE-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 VMNMAOFYRIIATE-UHFFFAOYSA-N 0.000 claims 1
• XWAPPKDYDOLMSL-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-ethoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OCC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 XWAPPKDYDOLMSL-UHFFFAOYSA-N 0.000 claims 1
• GRQGTZJSIOPATQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 GRQGTZJSIOPATQ-UHFFFAOYSA-N 0.000 claims 1
• XKMCTMIEONWRHD-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 XKMCTMIEONWRHD-UHFFFAOYSA-N 0.000 claims 1
• YUEXQWNDORRNFL-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-methoxyphenyl)prop-2-enyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1C(=C)CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 YUEXQWNDORRNFL-UHFFFAOYSA-N 0.000 claims 1
• PJFZIZIPSQQUNT-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-methoxyphenyl)propyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1C(C)CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 PJFZIZIPSQQUNT-UHFFFAOYSA-N 0.000 claims 1
• JXWKHDZQYDKIIO-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-methylphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 JXWKHDZQYDKIIO-UHFFFAOYSA-N 0.000 claims 1
• APCQXDPCCCVXTQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(4-propan-2-yloxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC(C)C)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 APCQXDPCCCVXTQ-UHFFFAOYSA-N 0.000 claims 1
• SXCLTFRQEZSXFQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 SXCLTFRQEZSXFQ-UHFFFAOYSA-N 0.000 claims 1
• KCZWAVRDVCIFCV-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-[3-(difluoromethoxy)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)OC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 KCZWAVRDVCIFCV-UHFFFAOYSA-N 0.000 claims 1
• PHIPOUNMHDRJGI-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-[3-(trifluoromethoxy)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)(F)OC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 PHIPOUNMHDRJGI-UHFFFAOYSA-N 0.000 claims 1
• VFTHPJWTZAPDRL-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 VFTHPJWTZAPDRL-UHFFFAOYSA-N 0.000 claims 1
• GYAMWMPCEMDSNC-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-[4-(difluoromethoxy)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC(F)F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 GYAMWMPCEMDSNC-UHFFFAOYSA-N 0.000 claims 1
• KLSSJRFDVRTUOC-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 KLSSJRFDVRTUOC-UHFFFAOYSA-N 0.000 claims 1
• ITMWWWQQRDVHFI-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-fluoro-2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(C(F)CN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 ITMWWWQQRDVHFI-UHFFFAOYSA-N 0.000 claims 1
• JQXXWZLQLBDQHL-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[2-fluoro-2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1C(F)CN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 JQXXWZLQLBDQHL-UHFFFAOYSA-N 0.000 claims 1
• IFXXKFLHCJAGEJ-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[3-(2-methoxyphenyl)propyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC=C1CCCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 IFXXKFLHCJAGEJ-UHFFFAOYSA-N 0.000 claims 1
• DMMSAKSAHSUBKU-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[3-(3-methoxyphenyl)propyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)=C1 DMMSAKSAHSUBKU-UHFFFAOYSA-N 0.000 claims 1
• HJTXVAVBBIWREO-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[3-(4-methoxyphenyl)propyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCCN1CCN(C=2SN=C(N=2)C=2C=CC(Cl)=CC=2)CC1 HJTXVAVBBIWREO-UHFFFAOYSA-N 0.000 claims 1
• UONKAGAAOKIYRY-UHFFFAOYSA-N 3-(4-chlorophenyl)-5-[4-[[1-(4-chlorophenyl)cyclopropyl]methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1C1=NSC(N2CCN(CC3(CC3)C=3C=CC(Cl)=CC=3)CC2)=N1 UONKAGAAOKIYRY-UHFFFAOYSA-N 0.000 claims 1
• VJJPADFYBLRWOJ-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CC=NC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 VJJPADFYBLRWOJ-UHFFFAOYSA-N 0.000 claims 1
• XLJVCIOAOMVEIL-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)CC1 XLJVCIOAOMVEIL-UHFFFAOYSA-N 0.000 claims 1
• ANGAZJOPUVYRJS-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)=C1 ANGAZJOPUVYRJS-UHFFFAOYSA-N 0.000 claims 1
• CBPBVWKZWPCPHP-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)CC1 CBPBVWKZWPCPHP-UHFFFAOYSA-N 0.000 claims 1
• GYGAXXGKYRHRNT-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)CC1 GYGAXXGKYRHRNT-UHFFFAOYSA-N 0.000 claims 1
• RWWSJERQLRBPFV-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)CC1 RWWSJERQLRBPFV-UHFFFAOYSA-N 0.000 claims 1
• NWDZATBGZPTXOE-UHFFFAOYSA-N 3-(4-chloropyridin-2-yl)-5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)=C1 NWDZATBGZPTXOE-UHFFFAOYSA-N 0.000 claims 1
• YNZKQMFSAVRKQY-UHFFFAOYSA-N 3-(4-fluorophenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(F)=CC=2)=C1 YNZKQMFSAVRKQY-UHFFFAOYSA-N 0.000 claims 1
• SGUOHQMLJKPWCH-UHFFFAOYSA-N 3-(4-fluorophenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(F)=CC=2)CC1 SGUOHQMLJKPWCH-UHFFFAOYSA-N 0.000 claims 1
• LOOUDAQKWBKPFA-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1C1=NSC(N2CCN(CCC=3C=C(OC)C=CC=3)CC2)=N1 LOOUDAQKWBKPFA-UHFFFAOYSA-N 0.000 claims 1
• RTRNKHMSPBSNIR-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(OC)=CC=2)CC1 RTRNKHMSPBSNIR-UHFFFAOYSA-N 0.000 claims 1
• QIYOONSAXLYGTF-UHFFFAOYSA-N 3-(4-methylphenyl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 QIYOONSAXLYGTF-UHFFFAOYSA-N 0.000 claims 1
• IVBUCEWGWBYKFT-UHFFFAOYSA-N 3-(4-methylphenyl)-5-[4-(3-phenylpropyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C)=CC=C1C1=NSC(N2CCN(CCCC=3C=CC=CC=3)CC2)=N1 IVBUCEWGWBYKFT-UHFFFAOYSA-N 0.000 claims 1
• HHGGLQNGGGLCAG-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound N1=CC(Cl)=CC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 HHGGLQNGGGLCAG-UHFFFAOYSA-N 0.000 claims 1
• WTGLPFLGFOXSHD-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2N=CC(Cl)=CC=2)CC1 WTGLPFLGFOXSHD-UHFFFAOYSA-N 0.000 claims 1
• BSKZJBXUIBCRGY-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC(Cl)=CC=2)CC1 BSKZJBXUIBCRGY-UHFFFAOYSA-N 0.000 claims 1
• DLTWNFYDNIORSZ-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC(Cl)=CC=2)CC1 DLTWNFYDNIORSZ-UHFFFAOYSA-N 0.000 claims 1
• ZGLHRXLFUFOAOA-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CN=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 ZGLHRXLFUFOAOA-UHFFFAOYSA-N 0.000 claims 1
• FUVMQXYDHZILFN-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 FUVMQXYDHZILFN-UHFFFAOYSA-N 0.000 claims 1
• FHXGKEPQLJHECP-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)=C1 FHXGKEPQLJHECP-UHFFFAOYSA-N 0.000 claims 1
• QCBUXTAGMPDOOG-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 QCBUXTAGMPDOOG-UHFFFAOYSA-N 0.000 claims 1
• JMFQJCFTOUKUFW-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 JMFQJCFTOUKUFW-UHFFFAOYSA-N 0.000 claims 1
• VOZVTRUSWKUZTC-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 VOZVTRUSWKUZTC-UHFFFAOYSA-N 0.000 claims 1
• JCSYYFDCWIRCFS-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-(oxan-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound ClC1=CN=CC(C=2N=C(SN=2)N2CCN(CCC3CCOCC3)CC2)=C1 JCSYYFDCWIRCFS-UHFFFAOYSA-N 0.000 claims 1
• QNHVBCOENHFRBI-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)=C1 QNHVBCOENHFRBI-UHFFFAOYSA-N 0.000 claims 1
• FIPDTTPGCFDVSL-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)-5-[4-[2-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 FIPDTTPGCFDVSL-UHFFFAOYSA-N 0.000 claims 1
• BDEVASZJRAKPCS-UHFFFAOYSA-N 3-(6-methylpyridazin-4-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound N1=NC(C)=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 BDEVASZJRAKPCS-UHFFFAOYSA-N 0.000 claims 1
• CBWOGTUCAFNVQB-UHFFFAOYSA-N 3-(6-methylpyridin-3-yl)-5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 CBWOGTUCAFNVQB-UHFFFAOYSA-N 0.000 claims 1
• OXBRZORDNXPFBC-UHFFFAOYSA-N 3-[5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound N#CC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC=CC=3)CC2)=C1 OXBRZORDNXPFBC-UHFFFAOYSA-N 0.000 claims 1
• KHQWDMQVMFWDBB-UHFFFAOYSA-N 3-[5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 KHQWDMQVMFWDBB-UHFFFAOYSA-N 0.000 claims 1
• BCOGWFLHQFQDLO-UHFFFAOYSA-N 3-[5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)=C1 BCOGWFLHQFQDLO-UHFFFAOYSA-N 0.000 claims 1
• NAIDKLYBNNOZLK-UHFFFAOYSA-N 3-[5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 NAIDKLYBNNOZLK-UHFFFAOYSA-N 0.000 claims 1
• WYHRMHYDSMGNOQ-UHFFFAOYSA-N 3-[5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 WYHRMHYDSMGNOQ-UHFFFAOYSA-N 0.000 claims 1
• XPNZMQLXOFWJQE-UHFFFAOYSA-N 3-[5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 XPNZMQLXOFWJQE-UHFFFAOYSA-N 0.000 claims 1
• MEHZXXGPHPVZOI-UHFFFAOYSA-N 3-[5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 MEHZXXGPHPVZOI-UHFFFAOYSA-N 0.000 claims 1
• NMAOKQYIZGGDDE-UHFFFAOYSA-N 3-[5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C=CC=2)C#N)CC1 NMAOKQYIZGGDDE-UHFFFAOYSA-N 0.000 claims 1
• XCNUOOIGNHYSEF-UHFFFAOYSA-N 4-[5-[4-(2-phenylethyl)piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=NSC(N2CCN(CCC=3C=CC=CC=3)CC2)=N1 XCNUOOIGNHYSEF-UHFFFAOYSA-N 0.000 claims 1
• AFLUYBLGMOXKNI-UHFFFAOYSA-N 4-[5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound CC1=CC=CC=C1CN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 AFLUYBLGMOXKNI-UHFFFAOYSA-N 0.000 claims 1
• WROXPPZUVFYEEK-UHFFFAOYSA-N 4-[5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)=C1 WROXPPZUVFYEEK-UHFFFAOYSA-N 0.000 claims 1
• LNHLLRPXBGLNGR-UHFFFAOYSA-N 4-[5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=C(F)C(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 LNHLLRPXBGLNGR-UHFFFAOYSA-N 0.000 claims 1
• KKZCJEJXBUIJRQ-UHFFFAOYSA-N 4-[5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 KKZCJEJXBUIJRQ-UHFFFAOYSA-N 0.000 claims 1
• YSCFZVKOTPSHNK-UHFFFAOYSA-N 4-[5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 YSCFZVKOTPSHNK-UHFFFAOYSA-N 0.000 claims 1
• VFDLCECTBRUJKK-UHFFFAOYSA-N 4-[5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 VFDLCECTBRUJKK-UHFFFAOYSA-N 0.000 claims 1
• IPXARVDMBRYGLQ-UHFFFAOYSA-N 4-[5-[4-[2-(6-methoxypyridin-3-yl)ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=NC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 IPXARVDMBRYGLQ-UHFFFAOYSA-N 0.000 claims 1
• JDKGSDNMKCITHY-UHFFFAOYSA-N 4-[5-[4-[2-[3-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound FC(F)(F)C1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)=C1 JDKGSDNMKCITHY-UHFFFAOYSA-N 0.000 claims 1
• QJLDYOCSBGGQQR-UHFFFAOYSA-N 4-[5-[4-[2-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]-1,2,4-thiadiazol-3-yl]benzonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(=CC=2)C#N)CC1 QJLDYOCSBGGQQR-UHFFFAOYSA-N 0.000 claims 1
• DPRRPJMKGGTIQE-UHFFFAOYSA-N 5-[4-(2-cyclohexylethyl)piperazin-1-yl]-3-(3,4-difluorophenyl)-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1C1=NSC(N2CCN(CCC3CCCCC3)CC2)=N1 DPRRPJMKGGTIQE-UHFFFAOYSA-N 0.000 claims 1
• VEWYBQSPGHOWFE-UHFFFAOYSA-N 5-[4-(2-cyclohexylethyl)piperazin-1-yl]-3-(3-fluorophenyl)-1,2,4-thiadiazole Chemical compound FC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC3CCCCC3)CC2)=C1 VEWYBQSPGHOWFE-UHFFFAOYSA-N 0.000 claims 1
• VIWURBQFWJZQQI-UHFFFAOYSA-N 5-[4-[(2,4-dichlorophenyl)methyl]piperazin-1-yl]-3-(4-methylphenyl)-1,2,4-thiadiazole Chemical compound C1=CC(C)=CC=C1C1=NSC(N2CCN(CC=3C(=CC(Cl)=CC=3)Cl)CC2)=N1 VIWURBQFWJZQQI-UHFFFAOYSA-N 0.000 claims 1
• KCHTVGXXHFPHAS-UHFFFAOYSA-N 5-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC=C1C1=NSC(N2CCN(CC=3C(=CC=CC=3)C)CC2)=N1 KCHTVGXXHFPHAS-UHFFFAOYSA-N 0.000 claims 1
• BYJWWMRMSILVJH-UHFFFAOYSA-N 5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-3-(2-methylpyridin-4-yl)-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=C(C)N=CC=2)=C1 BYJWWMRMSILVJH-UHFFFAOYSA-N 0.000 claims 1
• AUWWMAJCHUCBRL-UHFFFAOYSA-N 5-[4-[2-(2-methoxypyridin-4-yl)ethyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=NC(OC)=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=NC(C)=CC=2)=C1 AUWWMAJCHUCBRL-UHFFFAOYSA-N 0.000 claims 1
• KWQUTMZFSREIMI-UHFFFAOYSA-N 5-[4-[2-(3,4-dichlorophenyl)ethyl]piperazin-1-yl]-3-(4-methylphenyl)-1,2,4-thiadiazole Chemical compound C1=CC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=C(Cl)C(Cl)=CC=3)CC2)=N1 KWQUTMZFSREIMI-UHFFFAOYSA-N 0.000 claims 1
• ZOAIGBASANBVKB-UHFFFAOYSA-N 5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-3-(3-fluorophenyl)-1,2,4-thiadiazole Chemical compound FC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=C(F)C(F)=CC=3)CC2)=C1 ZOAIGBASANBVKB-UHFFFAOYSA-N 0.000 claims 1
• ZAJHPBXADZXBOL-UHFFFAOYSA-N 5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridazin-4-yl)-1,2,4-thiadiazole Chemical compound N1=NC(C)=CC(C=2N=C(SN=2)N2CCN(CCC=3C=C(F)C(F)=CC=3)CC2)=C1 ZAJHPBXADZXBOL-UHFFFAOYSA-N 0.000 claims 1
• OXIVQBKCCZZCJB-UHFFFAOYSA-N 5-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=C(F)C(F)=CC=3)CC2)=N1 OXIVQBKCCZZCJB-UHFFFAOYSA-N 0.000 claims 1
• XZKLXVYQFWRIHT-UHFFFAOYSA-N 5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-3-(4-methylphenyl)-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(C)=CC=2)=C1 XZKLXVYQFWRIHT-UHFFFAOYSA-N 0.000 claims 1
• PJRTWGIUWXGQNW-UHFFFAOYSA-N 5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=CC(OC(F)(F)F)=CC=2)=C1 PJRTWGIUWXGQNW-UHFFFAOYSA-N 0.000 claims 1
• YOLQXXPKZZLEMQ-UHFFFAOYSA-N 5-[4-[2-(3-methoxyphenyl)ethyl]piperazin-1-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-thiadiazole Chemical compound COC1=CC=CC(CCN2CCN(CC2)C=2SN=C(N=2)C=2C=NC(=CC=2)C(F)(F)F)=C1 YOLQXXPKZZLEMQ-UHFFFAOYSA-N 0.000 claims 1
• SLVMOAYITWPWDC-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(2-chloropyridin-4-yl)-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)N=CC=2)CC1 SLVMOAYITWPWDC-UHFFFAOYSA-N 0.000 claims 1
• NVDIOCYCRTWTCV-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(3,4-difluorophenyl)-1,2,4-thiadiazole Chemical compound C1=C(F)C(F)=CC=C1C1=NSC(N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=N1 NVDIOCYCRTWTCV-UHFFFAOYSA-N 0.000 claims 1
• AKAXVOJBJXZRLU-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(3-fluorophenyl)-1,2,4-thiadiazole Chemical compound FC1=CC=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=C1 AKAXVOJBJXZRLU-UHFFFAOYSA-N 0.000 claims 1
• XGMDSLKBKRSWMW-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(4-chloropyridin-2-yl)-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC=C(Cl)C=2)CC1 XGMDSLKBKRSWMW-UHFFFAOYSA-N 0.000 claims 1
• JPSUVIQPVUITHA-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(5-chloropyridin-2-yl)-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2N=CC(Cl)=CC=2)CC1 JPSUVIQPVUITHA-UHFFFAOYSA-N 0.000 claims 1
• VXVPSNWJYNOHLU-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(5-chloropyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=CC(Cl)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(Cl)C=NC=2)CC1 VXVPSNWJYNOHLU-UHFFFAOYSA-N 0.000 claims 1
• NIMAJHRRNBVJKJ-UHFFFAOYSA-N 5-[4-[2-(4-chlorophenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=CC(Cl)=CC=3)CC2)=N1 NIMAJHRRNBVJKJ-UHFFFAOYSA-N 0.000 claims 1
• NNZMSYUYNMBCHA-UHFFFAOYSA-N 5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-3-(2-methylpyrimidin-5-yl)-1,2,4-thiadiazole Chemical compound C1=NC(C)=NC=C1C1=NSC(N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 NNZMSYUYNMBCHA-UHFFFAOYSA-N 0.000 claims 1
• MOVYRJRQYQLSGS-UHFFFAOYSA-N 5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridazin-4-yl)-1,2,4-thiadiazole Chemical compound N1=NC(C)=CC(C=2N=C(SN=2)N2CCN(CCC=3C=CC(F)=CC=3)CC2)=C1 MOVYRJRQYQLSGS-UHFFFAOYSA-N 0.000 claims 1
• MUOYGOBEGXBYGI-UHFFFAOYSA-N 5-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=NC(C)=CC=C1C1=NSC(N2CCN(CCC=3C=CC(F)=CC=3)CC2)=N1 MUOYGOBEGXBYGI-UHFFFAOYSA-N 0.000 claims 1
• CKQWAMRELQYICT-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-(2-methylpyrimidin-5-yl)-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=NC(C)=NC=2)CC1 CKQWAMRELQYICT-UHFFFAOYSA-N 0.000 claims 1
• PQLYJHGHEWKWOD-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-(4-methylphenyl)-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(C)=CC=2)CC1 PQLYJHGHEWKWOD-UHFFFAOYSA-N 0.000 claims 1
• JPOCADXEETVJIZ-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridazin-4-yl)-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=C(C)N=NC=2)CC1 JPOCADXEETVJIZ-UHFFFAOYSA-N 0.000 claims 1
• DBJLSDMZKVGBDX-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-(6-methylpyridin-3-yl)-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=NC(C)=CC=2)CC1 DBJLSDMZKVGBDX-UHFFFAOYSA-N 0.000 claims 1
• URZSYFLQKDSRGU-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CC(OC(F)(F)F)=CC=2)CC1 URZSYFLQKDSRGU-UHFFFAOYSA-N 0.000 claims 1
• JVDIGUBFJXDVSK-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-[6-(trifluoromethyl)pyridin-3-yl]-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=NC(=CC=2)C(F)(F)F)CC1 JVDIGUBFJXDVSK-UHFFFAOYSA-N 0.000 claims 1
• JKINLTJKGHLRNQ-UHFFFAOYSA-N 5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-3-pyridin-4-yl-1,2,4-thiadiazole Chemical compound C1=CC(OC)=CC=C1CCN1CCN(C=2SN=C(N=2)C=2C=CN=CC=2)CC1 JKINLTJKGHLRNQ-UHFFFAOYSA-N 0.000 claims 1
• MRBXVNZKBGWPGS-UHFFFAOYSA-N FC1=CC(=C(C=C1)C1=NSC(=N1)N1CCN(CC1)CCC1=CC=C(C=C1)OC)OC.FC1=CC(=C(C=C1)C1=NSC(=N1)N1CCN(CC1)CCC1=CC(=CC=C1)OC)OC Chemical compound FC1=CC(=C(C=C1)C1=NSC(=N1)N1CCN(CC1)CCC1=CC=C(C=C1)OC)OC.FC1=CC(=C(C=C1)C1=NSC(=N1)N1CCN(CC1)CCC1=CC(=CC=C1)OC)OC MRBXVNZKBGWPGS-UHFFFAOYSA-N 0.000 claims 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• 230000002776 aggregation Effects 0.000 abstract description 14
• 238000004220 aggregation Methods 0.000 abstract description 14
• 231100000433 cytotoxic Toxicity 0.000 abstract description 4
• 230000001472 cytotoxic effect Effects 0.000 abstract description 4
• 229960005141 piperazine Drugs 0.000 description 753
• 230000015572 biosynthetic process Effects 0.000 description 176
• 238000003786 synthesis reaction Methods 0.000 description 176
• 239000007787 solid Substances 0.000 description 121
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 93
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
• 102100040243 Microtubule-associated protein tau Human genes 0.000 description 49
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 38
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 33
• 210000004027 cell Anatomy 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• 239000003921 oil Substances 0.000 description 20
• 235000019198 oils Nutrition 0.000 description 20
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 16
• FOVOGDCYFOXEKN-UHFFFAOYSA-N 1-[2-(4-methoxyphenyl)ethyl]piperazine;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1CCN1CCNCC1 FOVOGDCYFOXEKN-UHFFFAOYSA-N 0.000 description 15
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
• VQRBXYBBGHOGFT-UHFFFAOYSA-N 1-(chloromethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CCl VQRBXYBBGHOGFT-UHFFFAOYSA-N 0.000 description 12
• 208000034799 Tauopathies Diseases 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 239000000126 substance Substances 0.000 description 12
• ZXYICRUHFGEWJE-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)ethyl]piperazine;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC(CCN2CCNCC2)=C1 ZXYICRUHFGEWJE-UHFFFAOYSA-N 0.000 description 11
• 238000001704 evaporation Methods 0.000 description 11
• 230000008020 evaporation Effects 0.000 description 11
• XCKJCCCKEWTUIV-UHFFFAOYSA-N 4-(2-bromoethyl)-1,2-difluorobenzene Chemical compound FC1=CC=C(CCBr)C=C1F XCKJCCCKEWTUIV-UHFFFAOYSA-N 0.000 description 10
• 230000002378 acidificating effect Effects 0.000 description 10
• 239000000460 chlorine Substances 0.000 description 10
• 239000012044 organic layer Substances 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 108090000623 proteins and genes Proteins 0.000 description 9
• 239000000377 silicon dioxide Substances 0.000 description 9
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 9
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 8
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 238000006366 phosphorylation reaction Methods 0.000 description 8
• 102000004169 proteins and genes Human genes 0.000 description 8
• 239000000243 solution Substances 0.000 description 8
• AZLYAPKPZBXCGX-UHFFFAOYSA-N 1-(2-bromoethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCBr)=C1 AZLYAPKPZBXCGX-UHFFFAOYSA-N 0.000 description 7
• 239000007832 Na2SO4 Substances 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 239000000969 carrier Substances 0.000 description 7
• 238000004440 column chromatography Methods 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 102000013498 tau Proteins Human genes 0.000 description 7
• 108010026424 tau Proteins Proteins 0.000 description 7
• 150000004867 thiadiazoles Chemical class 0.000 description 7
• JWSRGCWCXUCWBJ-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1CCC1=CC=CC=C1 JWSRGCWCXUCWBJ-UHFFFAOYSA-N 0.000 description 6
• HDMIQDOSXQQYBE-UHFFFAOYSA-N 5-(2-bromoethyl)-2-methoxypyridine Chemical compound COC1=CC=C(CCBr)C=N1 HDMIQDOSXQQYBE-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 231100000135 cytotoxicity Toxicity 0.000 description 6
• 230000003013 cytotoxicity Effects 0.000 description 6
• 239000006260 foam Substances 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• YAFMYKFAUNCQPU-UHFFFAOYSA-N 1-(2-bromoethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CCBr)C=C1 YAFMYKFAUNCQPU-UHFFFAOYSA-N 0.000 description 5
• IWMBLVYJXPYLPN-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]piperazine;dihydrochloride Chemical compound Cl.Cl.C1=CC(Cl)=CC=C1CCN1CCNCC1 IWMBLVYJXPYLPN-UHFFFAOYSA-N 0.000 description 5
• BJMPGMOWXAYATG-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]piperazine;dihydrochloride Chemical compound Cl.Cl.C1=CC(F)=CC=C1CCN1CCNCC1 BJMPGMOWXAYATG-UHFFFAOYSA-N 0.000 description 5
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 5
• JXFHGHFHEXTLOL-UHFFFAOYSA-N 4-(2-bromoethyl)-2-methoxypyridine Chemical compound COC1=CC(CCBr)=CC=N1 JXFHGHFHEXTLOL-UHFFFAOYSA-N 0.000 description 5
• SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 210000002569 neuron Anatomy 0.000 description 5
• 229930002330 retinoic acid Natural products 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 229960001727 tretinoin Drugs 0.000 description 5
• FLRUNCJXOVYWDH-UHFFFAOYSA-N 1-(2-bromoethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCBr)C=C1 FLRUNCJXOVYWDH-UHFFFAOYSA-N 0.000 description 4
• JRQAAYVLPPGEHT-UHFFFAOYSA-N 2-bromoethylcyclohexane Chemical compound BrCCC1CCCCC1 JRQAAYVLPPGEHT-UHFFFAOYSA-N 0.000 description 4
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 4
• 239000001828 Gelatine Substances 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 239000000825 pharmaceutical preparation Substances 0.000 description 4
• 150000004885 piperazines Chemical class 0.000 description 4
• 238000002953 preparative HPLC Methods 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• UZKQKTLIRNYOBG-UHFFFAOYSA-N tert-butyl 4-(3-bromo-1,2,4-thiadiazol-5-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC(Br)=NS1 UZKQKTLIRNYOBG-UHFFFAOYSA-N 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 230000001988 toxicity Effects 0.000 description 4
• 231100000419 toxicity Toxicity 0.000 description 4
• WTCVMJLGKMOROW-UHFFFAOYSA-N 1-(2-bromoethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CCBr)C=C1 WTCVMJLGKMOROW-UHFFFAOYSA-N 0.000 description 3
• OXHPTABOQVHKLN-UHFFFAOYSA-N 1-(2-bromoethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCBr)C=C1 OXHPTABOQVHKLN-UHFFFAOYSA-N 0.000 description 3
• MACVYUROJLHHKH-UHFFFAOYSA-N 1-[2-(2-methoxypyridin-4-yl)ethyl]piperazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1=NC(OC)=CC(CCN2CCNCC2)=C1 MACVYUROJLHHKH-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical group COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 102000029749 Microtubule Human genes 0.000 description 3
• 108091022875 Microtubule Proteins 0.000 description 3
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000012894 fetal calf serum Substances 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
• 210000001589 microsome Anatomy 0.000 description 3
• 210000004688 microtubule Anatomy 0.000 description 3
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
• RYFZYYUIAZYQLC-UHFFFAOYSA-N perchloromethyl mercaptan Chemical compound ClSC(Cl)(Cl)Cl RYFZYYUIAZYQLC-UHFFFAOYSA-N 0.000 description 3
• AUYNWRLEXAPZAJ-UHFFFAOYSA-N piperazine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CNCCN1 AUYNWRLEXAPZAJ-UHFFFAOYSA-N 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• 229920005862 polyol Polymers 0.000 description 3
• 150000003077 polyols Chemical class 0.000 description 3
• 235000017550 sodium carbonate Nutrition 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 3
• XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 2
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 2
• UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 2
• LQDHVNHVHAYANB-UHFFFAOYSA-N 1-(2-bromoethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCBr)=C1 LQDHVNHVHAYANB-UHFFFAOYSA-N 0.000 description 2
• XQJAHBHCLXUGEP-UHFFFAOYSA-N 2-bromo-1-(4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CBr)C=C1 XQJAHBHCLXUGEP-UHFFFAOYSA-N 0.000 description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
• CEUHPOVLEQUFCC-UHFFFAOYSA-N 3,5-dichloro-1,2,4-thiadiazole Chemical compound ClC1=NSC(Cl)=N1 CEUHPOVLEQUFCC-UHFFFAOYSA-N 0.000 description 2
• CXUWGEWQRCXJDC-UHFFFAOYSA-N 3-bromo-5-chloro-1,2,4-thiadiazole Chemical compound ClC1=NC(Br)=NS1 CXUWGEWQRCXJDC-UHFFFAOYSA-N 0.000 description 2
• HDJRNMVQLGESEX-UHFFFAOYSA-N 4-chlorothiadiazole Chemical class ClC1=CSN=N1 HDJRNMVQLGESEX-UHFFFAOYSA-N 0.000 description 2
• 208000000044 Amnesia Diseases 0.000 description 2
• 101150051438 CYP gene Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 125000003275 alpha amino acid group Chemical group 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 208000017004 dementia pugilistica Diseases 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 230000008034 disappearance Effects 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 239000003925 fat Substances 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 2
• 230000006951 hyperphosphorylation Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 125000005647 linker group Chemical group 0.000 description 2
• 210000001853 liver microsome Anatomy 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 230000003228 microsomal effect Effects 0.000 description 2
• 230000009456 molecular mechanism Effects 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 230000007991 neuronal integrity Effects 0.000 description 2
• 231100000189 neurotoxic Toxicity 0.000 description 2
• 230000002887 neurotoxic effect Effects 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 208000002593 pantothenate kinase-associated neurodegeneration Diseases 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• RMGYQBHKEWWTOY-UHFFFAOYSA-N (3,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(F)=C1 RMGYQBHKEWWTOY-UHFFFAOYSA-N 0.000 description 1
• SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• QMAIOGFYFFJARE-UHFFFAOYSA-N (6-methylpyridine-3-carboximidoyl)azanium;chloride Chemical compound [Cl-].CC1=CC=C(C([NH3+])=N)C=N1 QMAIOGFYFFJARE-UHFFFAOYSA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical class C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• YINMBNZKJFUYLO-UHFFFAOYSA-N 1-(1h-pyrrol-2-yl)piperazine Chemical compound C1CNCCN1C1=CC=CN1 YINMBNZKJFUYLO-UHFFFAOYSA-N 0.000 description 1
• AECBVDLERUETKG-UHFFFAOYSA-N 1-(2-bromoethyl)-2-chlorobenzene Chemical compound ClC1=CC=CC=C1CCBr AECBVDLERUETKG-UHFFFAOYSA-N 0.000 description 1
• FQGDFWIQBCQXPS-UHFFFAOYSA-N 1-(2-bromoethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCBr FQGDFWIQBCQXPS-UHFFFAOYSA-N 0.000 description 1
• UIIJKBSUGZNVQN-UHFFFAOYSA-N 1-(2-bromoethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CCBr UIIJKBSUGZNVQN-UHFFFAOYSA-N 0.000 description 1
• CQRJXCNUPKDKQH-UHFFFAOYSA-N 1-(2-bromoethyl)-3-(difluoromethoxy)benzene Chemical compound FC(F)OC1=CC=CC(CCBr)=C1 CQRJXCNUPKDKQH-UHFFFAOYSA-N 0.000 description 1
• RZHWLCIKYSVRGJ-UHFFFAOYSA-N 1-(2-bromoethyl)-3-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC(CCBr)=C1 RZHWLCIKYSVRGJ-UHFFFAOYSA-N 0.000 description 1
• LKPWGXCMVLJRIK-UHFFFAOYSA-N 1-(2-bromoethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CCBr)=C1 LKPWGXCMVLJRIK-UHFFFAOYSA-N 0.000 description 1
• GLVSPVSJMYQIPJ-UHFFFAOYSA-N 1-(2-bromoethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CCBr)=C1 GLVSPVSJMYQIPJ-UHFFFAOYSA-N 0.000 description 1
• STQJFINZGUXVEX-UHFFFAOYSA-N 1-(2-bromoethyl)-3-methylbenzene Chemical compound CC1=CC=CC(CCBr)=C1 STQJFINZGUXVEX-UHFFFAOYSA-N 0.000 description 1
• ZXBGXQNGLVEFBJ-UHFFFAOYSA-N 1-(2-bromoethyl)-3-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC(CCBr)=C1 ZXBGXQNGLVEFBJ-UHFFFAOYSA-N 0.000 description 1
• HUAGKSUHLKYSRG-UHFFFAOYSA-N 1-(2-bromoethyl)-4-(difluoromethoxy)benzene Chemical compound FC(F)OC1=CC=C(CCBr)C=C1 HUAGKSUHLKYSRG-UHFFFAOYSA-N 0.000 description 1
• RYVDUZLLFJTDKF-UHFFFAOYSA-N 1-(2-bromoethyl)-4-ethoxybenzene Chemical compound CCOC1=CC=C(CCBr)C=C1 RYVDUZLLFJTDKF-UHFFFAOYSA-N 0.000 description 1
• JYRFCOBEWYKKJB-UHFFFAOYSA-N 1-(2-bromoethyl)-4-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=C(CCBr)C=C1 JYRFCOBEWYKKJB-UHFFFAOYSA-N 0.000 description 1
• LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 description 1
• VYKXBWXIOSLDQR-UHFFFAOYSA-N 1-[(2,4-dichlorophenyl)methyl]piperazine Chemical compound ClC1=CC(Cl)=CC=C1CN1CCNCC1 VYKXBWXIOSLDQR-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• OWINIGBJQWGIJU-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)ethyl]piperazine Chemical compound C1=C(Cl)C(Cl)=CC=C1CCN1CCNCC1 OWINIGBJQWGIJU-UHFFFAOYSA-N 0.000 description 1
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000003070 2-(2-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• UPUQEDRMMJOAKD-UHFFFAOYSA-N 2-(2-methoxypyridin-4-yl)ethanol Chemical compound COC1=CC(CCO)=CC=N1 UPUQEDRMMJOAKD-UHFFFAOYSA-N 0.000 description 1
• JABKESJVYSQBGF-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1-phenylethanone Chemical compound C1=CC(OC)=CC=C1CC(=O)C1=CC=CC=C1 JABKESJVYSQBGF-UHFFFAOYSA-N 0.000 description 1
• ITAQNNGDCNFGID-UHFFFAOYSA-N 2-bromo-1-(3-fluorophenyl)ethanone Chemical compound FC1=CC=CC(C(=O)CBr)=C1 ITAQNNGDCNFGID-UHFFFAOYSA-N 0.000 description 1
• IOOHBIFQNQQUFI-UHFFFAOYSA-N 2-bromo-1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(=O)CBr)=C1 IOOHBIFQNQQUFI-UHFFFAOYSA-N 0.000 description 1
• SONBKIBXOFXRHV-UHFFFAOYSA-N 2-chloropyridine-4-carboximidamide Chemical compound NC(=N)C1=CC=NC(Cl)=C1 SONBKIBXOFXRHV-UHFFFAOYSA-N 0.000 description 1
• NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 1
• UYPHFBKQVOALNA-UHFFFAOYSA-N 2-methoxybenzenecarboximidamide;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C(N)=N UYPHFBKQVOALNA-UHFFFAOYSA-N 0.000 description 1
• FFLPJEKRAYZAMU-UHFFFAOYSA-N 3,5-dichlorobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC(Cl)=CC(Cl)=C1 FFLPJEKRAYZAMU-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 1
• XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XKLOKJSAFAEHRR-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=C(OC(F)(F)F)C=C1 XKLOKJSAFAEHRR-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• ZYSUCPSLKDRMHS-UHFFFAOYSA-N 4-chloro-2-fluorobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=C(Cl)C=C1F ZYSUCPSLKDRMHS-UHFFFAOYSA-N 0.000 description 1
• HESAARZNMYTITM-UHFFFAOYSA-N 4-chloropyridine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC(Cl)=CC=N1 HESAARZNMYTITM-UHFFFAOYSA-N 0.000 description 1
• SSQJCWTYXQYGGN-UHFFFAOYSA-N 4-fluoro-2-methoxybenzenecarboximidamide;hydrochloride Chemical compound Cl.COC1=CC(F)=CC=C1C(N)=N SSQJCWTYXQYGGN-UHFFFAOYSA-N 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• MRKRYPWJHHBKHD-UHFFFAOYSA-N 5-chloro-3-(2-methoxyphenyl)-1,2,4-thiadiazole Chemical compound COC1=CC=CC=C1C1=NSC(Cl)=N1 MRKRYPWJHHBKHD-UHFFFAOYSA-N 0.000 description 1
• AIOJVZFDKUBUTE-UHFFFAOYSA-N 5-chloropyridine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=C(Cl)C=N1 AIOJVZFDKUBUTE-UHFFFAOYSA-N 0.000 description 1
• LATJFPJHQHOXEJ-UHFFFAOYSA-N 5-chloropyridine-3-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CN=CC(Cl)=C1 LATJFPJHQHOXEJ-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• HUKUESHULWUKHP-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=C(C(F)(F)F)N=C1 HUKUESHULWUKHP-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 208000037259 Amyloid Plaque Diseases 0.000 description 1
• 101000605172 Aspergillus niger (strain CBS 513.88 / FGSC A1513) Probable endopolygalacturonase E Proteins 0.000 description 1
• 101000605171 Aspergillus niger Endopolygalacturonase E Proteins 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 102000004308 Carboxylic Ester Hydrolases Human genes 0.000 description 1
• 108090000863 Carboxylic Ester Hydrolases Proteins 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 1
• 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 201000004066 Ganglioglioma Diseases 0.000 description 1
• 108010081348 HRT1 protein Hairy Proteins 0.000 description 1
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
• 206010022998 Irritability Diseases 0.000 description 1
• RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
• 208000009829 Lewy Body Disease Diseases 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
• 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
• 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
• 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
• 206010027951 Mood swings Diseases 0.000 description 1
• 208000001089 Multiple system atrophy Diseases 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 208000014060 Niemann-Pick disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 206010048327 Supranuclear palsy Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• IONKMFGAXKCLMI-UHFFFAOYSA-N [amino(pyridin-4-yl)methylidene]azanium;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=NC=C1 IONKMFGAXKCLMI-UHFFFAOYSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 230000016571 aggressive behavior Effects 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 206010002022 amyloidosis Diseases 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 208000013968 amyotrophic lateral sclerosis-parkinsonism-dementia complex Diseases 0.000 description 1
• 208000014450 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 Diseases 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 230000001857 anti-mycotic effect Effects 0.000 description 1
• 239000002543 antimycotic Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000007963 capsule composition Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 210000003092 coiled body Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 238000002784 cytotoxicity assay Methods 0.000 description 1
• 231100000263 cytotoxicity test Toxicity 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000003797 essential amino acid Substances 0.000 description 1
• 235000020776 essential amino acid Nutrition 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 239000013613 expression plasmid Substances 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 229930003944 flavone Natural products 0.000 description 1
• 150000002212 flavone derivatives Chemical class 0.000 description 1
• 235000011949 flavones Nutrition 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 201000005649 gangliocytoma Diseases 0.000 description 1
• 201000008361 ganglioneuroma Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 231100000171 higher toxicity Toxicity 0.000 description 1
• QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
• MTDUPZAXNYELOU-UHFFFAOYSA-N hydron;4-methylbenzenecarboximidamide;chloride Chemical compound Cl.CC1=CC=C(C(N)=N)C=C1 MTDUPZAXNYELOU-UHFFFAOYSA-N 0.000 description 1
• 230000003116 impacting effect Effects 0.000 description 1
• 210000003000 inclusion body Anatomy 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 125000002346 iodo group Chemical group I* 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
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• SAVQQRYWWAGSQW-UHFFFAOYSA-N n-methyl-n-(trifluoro-$l^{4}-sulfanyl)methanamine Chemical group CN(C)S(F)(F)F SAVQQRYWWAGSQW-UHFFFAOYSA-N 0.000 description 1
• 208000033510 neuroaxonal dystrophy Diseases 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 231100000989 no adverse effect Toxicity 0.000 description 1
• 230000001473 noxious effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 238000012430 stability testing Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-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
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• URAGJMBGNVOIJC-UHFFFAOYSA-N thiophene-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CS1 URAGJMBGNVOIJC-UHFFFAOYSA-N 0.000 description 1
• 229910052719 titanium Inorganic materials 0.000 description 1
• 239000010936 titanium Substances 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 208000009999 tuberous sclerosis Diseases 0.000 description 1
• VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 238000005550 wet granulation Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1