KR20110000749A - 신경변성 질환의 치료용 스피로 피페리딘류 - Google Patents

Info

Publication number

KR20110000749A

KR20110000749A KR1020107024794A KR20107024794A KR20110000749A KR 20110000749 A KR20110000749 A KR 20110000749A KR 1020107024794 A KR1020107024794 A KR 1020107024794A KR 20107024794 A KR20107024794 A KR 20107024794A KR 20110000749 A KR20110000749 A KR 20110000749A

Authority

KR

South Korea

Prior art keywords

methyl

thia

fluorophenyl

alkyl

triazaspiro

Prior art date

2008-05-05

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.)

Ceased

Links

• Espacenet
• Global Dossier
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• -1 Spiro piperidines Chemical class 0.000 title claims description 138
• 208000015122 neurodegenerative disease Diseases 0.000 title description 4
• 230000004770 neurodegeneration Effects 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 129
• 238000000034 method Methods 0.000 claims abstract description 64
• 150000003839 salts Chemical class 0.000 claims abstract description 47
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 145
• 125000001424 substituent group Chemical group 0.000 claims description 89
• 150000002367 halogens Chemical class 0.000 claims description 83
• 229910052736 halogen Inorganic materials 0.000 claims description 77
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 71
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 71
• 125000003118 aryl group Chemical group 0.000 claims description 57
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
• 125000001072 heteroaryl group Chemical group 0.000 claims description 44
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
• 229910052757 nitrogen Inorganic materials 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 30
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 24
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 21
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
• 125000003386 piperidinyl group Chemical group 0.000 claims description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 125000003342 alkenyl group Chemical group 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• CYNJHNQWUQFBEA-FDDCHVKYSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 CYNJHNQWUQFBEA-FDDCHVKYSA-N 0.000 claims description 11
• 241000124008 Mammalia Species 0.000 claims description 11
• 208000012902 Nervous system disease Diseases 0.000 claims description 9
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• QSOLHUVFBJBRHK-MUAVYFROSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-3-(pyridin-2-ylmethyl)-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(CC=4N=CC=CC=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 QSOLHUVFBJBRHK-MUAVYFROSA-N 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 208000025966 Neurological disease Diseases 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 230000000926 neurological effect Effects 0.000 claims description 7
• 208000020016 psychiatric disease Diseases 0.000 claims description 7
• 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 6
• 239000003693 atypical antipsychotic agent Substances 0.000 claims description 5
• 229940127236 atypical antipsychotics Drugs 0.000 claims description 5
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• UZWOFKFOTAZIFO-RBISFHTESA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-3-(pyrimidin-2-ylmethyl)-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(CC=4N=CC=CN=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 UZWOFKFOTAZIFO-RBISFHTESA-N 0.000 claims description 4
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• DWJUVHMOGMDYRQ-RXFWQSSRSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[[3-(4-methylpyridin-3-yl)phenyl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C=CC=2)C=2C(=CC=NC=2)C)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 DWJUVHMOGMDYRQ-RXFWQSSRSA-N 0.000 claims description 3
• 125000003282 alkyl amino group Chemical group 0.000 claims description 3
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
• ZXOHUCGZHMGSOU-RBISFHTESA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-(2-methylphenyl)phenyl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C=CC=2)C=2C(=CC=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZXOHUCGZHMGSOU-RBISFHTESA-N 0.000 claims description 2
• KZUCNHLHFYXYIH-OYHNWAKOSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-(trifluoromethyl)-2h-indazol-5-yl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C3C(=NNC3=CC=2)C(F)(F)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 KZUCNHLHFYXYIH-OYHNWAKOSA-N 0.000 claims description 2
• FBKPLPCTJVWUBC-AFJIDDCJSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-[(2-methyl-1,3-benzoxazol-6-yl)oxy]phenyl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(OC=3C=C4OC(C)=NC4=CC=3)C=CC=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 FBKPLPCTJVWUBC-AFJIDDCJSA-N 0.000 claims description 2
• QZUGLLTUPJXOEF-HTAPYJJXSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[4-(2-methylpropyl)-1,3-thiazol-5-yl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound N1=CSC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=C1CC(C)C QZUGLLTUPJXOEF-HTAPYJJXSA-N 0.000 claims description 2
• FSXGJLJJXJVZMS-KDYSTLNUSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-3-(1,2-oxazol-3-ylmethyl)-8-[(3-propan-2-yloxyphenyl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(CC4=NOC=C4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 FSXGJLJJXJVZMS-KDYSTLNUSA-N 0.000 claims description 2
• CPNYKYVZIZDRFM-KDYSTLNUSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-3-pyrimidin-2-yl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C=4N=CC=CN=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 CPNYKYVZIZDRFM-KDYSTLNUSA-N 0.000 claims description 2
• IMAPVYYXLMWACS-KDYSTLNUSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[[3-(2-methylphenyl)phenyl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C=CC=2)C=2C(=CC=CC=2)C)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 IMAPVYYXLMWACS-KDYSTLNUSA-N 0.000 claims description 2
• FUWIMDVZJVRXTN-BXKMTCNYSA-N (5r,7s)-8-[(3-ethyl-2h-indazol-5-yl)methyl]-1-(3-fluorophenyl)-3,7-dimethyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@]12CCN([C@H](C2)C)CC2=CC=C3NN=C(C3=C2)CC)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 FUWIMDVZJVRXTN-BXKMTCNYSA-N 0.000 claims description 2
• ZNJPYGAZHWKTMZ-AFMDSPMNSA-N (5r,7s)-8-[[3-(2-chlorophenyl)phenyl]methyl]-1-(3-fluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C=CC=2)C=2C(=CC=CC=2)Cl)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 ZNJPYGAZHWKTMZ-AFMDSPMNSA-N 0.000 claims description 2
• DFEKPRLLWWWLDM-RBTNQOKQSA-N (5r,7s)-8-[[3-(2-ethylphenyl)phenyl]methyl]-1-(3-fluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CCC1=CC=CC=C1C1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 DFEKPRLLWWWLDM-RBTNQOKQSA-N 0.000 claims description 2
• OSYQGIYTQMJNJN-XLNZFTOWSA-N (5r,7s)-8-[[3-[(2r)-butan-2-yl]oxyphenyl]methyl]-1-(3-fluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC[C@@H](C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 OSYQGIYTQMJNJN-XLNZFTOWSA-N 0.000 claims description 2
• IEUIEHMFISIHRH-GAJHUEQPSA-N (5r,7s)-8-[[4-(cyclobutylmethyl)-1,3-thiazol-5-yl]methyl]-1-(3-fluorophenyl)-3,7-dimethyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC2=C(N=CS2)CC2CCC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 IEUIEHMFISIHRH-GAJHUEQPSA-N 0.000 claims description 2
• ZQJULPZFMZOSLA-KSFYIVLOSA-N (5r,7s)-8-[[4-(cyclopropylmethyl)-1,3-thiazol-5-yl]methyl]-1-(3-fluorophenyl)-3,7-dimethyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC2=C(N=CS2)CC2CC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZQJULPZFMZOSLA-KSFYIVLOSA-N 0.000 claims description 2
• ZUBYHDWXQQPSEZ-UZTOHYMASA-N 2-(2-chlorophenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=CC=2)Cl)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZUBYHDWXQQPSEZ-UZTOHYMASA-N 0.000 claims description 2
• VHWOGUHJOISKNG-KCWXNJEJSA-N 2-(2-ethylphenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound CCC1=CC=CC=C1C1=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=CC=C1O VHWOGUHJOISKNG-KCWXNJEJSA-N 0.000 claims description 2
• UNITYWVLNLNBTD-UZTOHYMASA-N 2-(2-fluorophenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=CC=2)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 UNITYWVLNLNBTD-UZTOHYMASA-N 0.000 claims description 2
• RGTZYHRNQTXIMS-WTYVLRPYSA-N 2-(4-fluoro-2-methylphenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC(F)=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 RGTZYHRNQTXIMS-WTYVLRPYSA-N 0.000 claims description 2
• BAKGYLUMYDNTII-WTYVLRPYSA-N 2-(5-fluoro-2-methylphenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=C(F)C=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 BAKGYLUMYDNTII-WTYVLRPYSA-N 0.000 claims description 2
• SOJBMZPXFYLDJM-VBKZILBWSA-N 2-chloro-4-[[(5r,7s)-1-(3-fluorophenyl)-7-methyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(Cl)C(O)=CC=2)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 SOJBMZPXFYLDJM-VBKZILBWSA-N 0.000 claims description 2
• WYSAIGUNBIVZQV-CCLHPLFOSA-N 2-cyclohexyl-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C2CCCCC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 WYSAIGUNBIVZQV-CCLHPLFOSA-N 0.000 claims description 2
• PMSHTXDQONLZAH-AFMDSPMNSA-N 2-cyclopentyl-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C2CCCC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 PMSHTXDQONLZAH-AFMDSPMNSA-N 0.000 claims description 2
• VBOPGXQKDLUCGO-RBTNQOKQSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-(2-methylphenyl)phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 VBOPGXQKDLUCGO-RBTNQOKQSA-N 0.000 claims description 2
• UICGCQDWRACUBV-MHECFPHRSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 UICGCQDWRACUBV-MHECFPHRSA-N 0.000 claims description 2
• WBPLJGRIZTYLDG-GAJHUEQPSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-propan-2-yloxypyridin-3-ol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=N1 WBPLJGRIZTYLDG-GAJHUEQPSA-N 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
• 229940044551 receptor antagonist Drugs 0.000 claims description 2
• 239000002464 receptor antagonist Substances 0.000 claims description 2
• 150000002431 hydrogen Chemical group 0.000 claims 4
• 229940122041 Cholinesterase inhibitor Drugs 0.000 claims 1
• JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 claims 1
• 230000015572 biosynthetic process Effects 0.000 abstract description 14
• 239000000543 intermediate Substances 0.000 abstract description 14
• 238000003786 synthesis reaction Methods 0.000 abstract description 11
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• 239000000203 mixture Substances 0.000 description 31
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 28
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 26
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• 125000004432 carbon atom Chemical group C* 0.000 description 24
• 208000024827 Alzheimer disease Diseases 0.000 description 22
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• 239000000047 product Substances 0.000 description 20
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• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 17
• 125000002757 morpholinyl group Chemical group 0.000 description 16
• 238000002360 preparation method Methods 0.000 description 16
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• 238000005481 NMR spectroscopy Methods 0.000 description 14
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
• 239000003814 drug Substances 0.000 description 13
• 125000006413 ring segment Chemical group 0.000 description 13
• 101800001718 Amyloid-beta protein Proteins 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
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• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 10
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• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
• 229910000024 caesium carbonate Inorganic materials 0.000 description 10
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• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
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• 206010012289 Dementia Diseases 0.000 description 9
• 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 9
• 125000004429 atom Chemical group 0.000 description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
• 150000001721 carbon Chemical group 0.000 description 9
• 125000000623 heterocyclic group Chemical group 0.000 description 9
• 239000001301 oxygen Substances 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
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