CA2721786A1 - Novel class of spiro piperidines for the treatment of neurodegenerative diseases - Google Patents

Info

Publication number

CA2721786A1

CA2721786A1 CA2721786A CA2721786A CA2721786A1 CA 2721786 A1 CA2721786 A1 CA 2721786A1 CA 2721786 A CA2721786 A CA 2721786A CA 2721786 A CA2721786 A CA 2721786A CA 2721786 A1 CA2721786 A1 CA 2721786A1

Authority

CA

Canada

Prior art keywords

methyl

thia

triazaspiro

fluorophenyl

alkyl

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 35
• -1 class of spiro piperidines Chemical class 0.000 title claims description 135
• 208000015122 neurodegenerative disease Diseases 0.000 title description 5
• 230000004770 neurodegeneration Effects 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 137
• 238000000034 method Methods 0.000 claims abstract description 73
• 150000003839 salts Chemical class 0.000 claims abstract description 48
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 211
• 125000000217 alkyl group Chemical group 0.000 claims description 145
• 125000001424 substituent group Chemical group 0.000 claims description 88
• 150000002367 halogens Chemical group 0.000 claims description 83
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 81
• 229910052736 halogen Inorganic materials 0.000 claims description 77
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 74
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 70
• 125000003118 aryl group Chemical group 0.000 claims description 58
• 229910052757 nitrogen Inorganic materials 0.000 claims description 51
• 125000001072 heteroaryl group Chemical group 0.000 claims description 43
• 229910052799 carbon Inorganic materials 0.000 claims description 42
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
• 239000000203 mixture Substances 0.000 claims description 34
• 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 32
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 23
• 125000003386 piperidinyl group Chemical group 0.000 claims description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• CYNJHNQWUQFBEA-FDDCHVKYSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 CYNJHNQWUQFBEA-FDDCHVKYSA-N 0.000 claims description 13
• 241000124008 Mammalia Species 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 208000012902 Nervous system disease Diseases 0.000 claims description 8
• 208000025966 Neurological disease Diseases 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 230000000926 neurological effect Effects 0.000 claims description 8
• 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 6
• 208000020016 psychiatric disease Diseases 0.000 claims description 6
• QSOLHUVFBJBRHK-MUAVYFROSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(3-propan-2-yloxyphenyl)methyl]-3-(pyridin-2-ylmethyl)-2$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 5
• 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$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(CC=4N=CC=CN=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 UZWOFKFOTAZIFO-RBISFHTESA-N 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• DWJUVHMOGMDYRQ-RXFWQSSRSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[[3-(4-methylpyridin-3-yl)phenyl]methyl]-2$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
• 229940122041 Cholinesterase inhibitor Drugs 0.000 claims description 3
• 229940099433 NMDA receptor antagonist Drugs 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
• 201000010099 disease Diseases 0.000 claims description 3
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 3
• ZXOHUCGZHMGSOU-RBISFHTESA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-(2-methylphenyl)phenyl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C=CC=2)C=2C(=CC=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZXOHUCGZHMGSOU-RBISFHTESA-N 0.000 claims description 2
• FBKPLPCTJVWUBC-AFJIDDCJSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-[(2-methyl-1,3-benzoxazol-6-yl)oxy]phenyl]methyl]-2$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$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CCC1=CC=CC=C1C1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 DFEKPRLLWWWLDM-RBTNQOKQSA-N 0.000 claims description 2
• IEUIEHMFISIHRH-GAJHUEQPSA-N (5r,7s)-8-[[4-(cyclobutylmethyl)-1,3-thiazol-5-yl]methyl]-1-(3-fluorophenyl)-3,7-dimethyl-2$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$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound CCC1=CC=CC=C1C1=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=CC=C1O VHWOGUHJOISKNG-KCWXNJEJSA-N 0.000 claims description 2
• RGTZYHRNQTXIMS-WTYVLRPYSA-N 2-(4-fluoro-2-methylphenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$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$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C2CCCCC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 WYSAIGUNBIVZQV-CCLHPLFOSA-N 0.000 claims description 2
• ZWXIZDQZWWRRNN-KSFYIVLOSA-N 2-ethoxy-4-[[(5r,7s)-1-(3-fluorophenyl)-7-methyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C1=C(O)C(OCC)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=C1 ZWXIZDQZWWRRNN-KSFYIVLOSA-N 0.000 claims description 2
• VBOPGXQKDLUCGO-RBTNQOKQSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-(2-methylphenyl)phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 VBOPGXQKDLUCGO-RBTNQOKQSA-N 0.000 claims description 2
• DTCFCCRFGNEDCK-UQBPGWFLSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-(2-methylpropyl)phenol Chemical compound C1=C(O)C(CC(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 DTCFCCRFGNEDCK-UQBPGWFLSA-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
• 150000002431 hydrogen Chemical group 0.000 claims 4
• KZUCNHLHFYXYIH-OYHNWAKOSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[3-(trifluoromethyl)-2h-indazol-5-yl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C3C(=NNC3=CC=2)C(F)(F)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 KZUCNHLHFYXYIH-OYHNWAKOSA-N 0.000 claims 1
• OSYQGIYTQMJNJN-XLNZFTOWSA-N (5r,7s)-8-[[3-[(2r)-butan-2-yl]oxyphenyl]methyl]-1-(3-fluorophenyl)-7-methyl-2$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 1
• UNITYWVLNLNBTD-UZTOHYMASA-N 2-(2-fluorophenyl)-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]phenol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(C(O)=CC=2)C=2C(=CC=CC=2)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 UNITYWVLNLNBTD-UZTOHYMASA-N 0.000 claims 1
• PMSHTXDQONLZAH-AFMDSPMNSA-N 2-cyclopentyl-4-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$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 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 16
• 238000003786 synthesis reaction Methods 0.000 abstract description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 71
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
• 125000005842 heteroatom Chemical group 0.000 description 22
• 208000024827 Alzheimer disease Diseases 0.000 description 21
• 150000001299 aldehydes Chemical class 0.000 description 20
• 239000000047 product Substances 0.000 description 20
• 239000000243 solution Substances 0.000 description 20
• 239000002585 base Substances 0.000 description 18
• 238000010898 silica gel chromatography Methods 0.000 description 18
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
• 150000001721 carbon Chemical group 0.000 description 17
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
• 125000002757 morpholinyl group Chemical group 0.000 description 16
• 125000004432 carbon atom Chemical group C* 0.000 description 15
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 14
• 239000000543 intermediate Substances 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 125000006413 ring segment Chemical group 0.000 description 13
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• 238000005481 NMR spectroscopy Methods 0.000 description 11
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• 235000019439 ethyl acetate Nutrition 0.000 description 11
• 125000000623 heterocyclic group Chemical group 0.000 description 11
• 239000007787 solid Substances 0.000 description 11
• 239000000758 substrate Substances 0.000 description 11
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
• 101800001718 Amyloid-beta protein Proteins 0.000 description 10
• 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 10
• 208000002193 Pain Diseases 0.000 description 10
• 208000010877 cognitive disease Diseases 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 9
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 9
• 206010012289 Dementia Diseases 0.000 description 9
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
• 239000001301 oxygen Substances 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• 229910052717 sulfur Chemical group 0.000 description 9
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 8
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 8
• 102100021257 Beta-secretase 1 Human genes 0.000 description 8
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 125000002837 carbocyclic group Chemical group 0.000 description 8
• 238000003776 cleavage reaction Methods 0.000 description 8
• 230000007017 scission Effects 0.000 description 8
• 239000011593 sulfur Chemical group 0.000 description 8
• CYKZAXPPHLTJOC-GXFFZTMASA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C1CN[C@@H](C)C[C@]11N(C=2C=C(F)C=CC=2)S(=O)(=O)NC1 CYKZAXPPHLTJOC-GXFFZTMASA-N 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 230000029936 alkylation Effects 0.000 description 7
• 238000005804 alkylation reaction Methods 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 210000004556 brain Anatomy 0.000 description 7
• 229940125782 compound 2 Drugs 0.000 description 7
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• VCZKTIKPEDMZNW-UHFFFAOYSA-N O=S(=O)=S Chemical group O=S(=O)=S VCZKTIKPEDMZNW-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 229940125904 compound 1 Drugs 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 238000004949 mass spectrometry Methods 0.000 description 6
• 150000007524 organic acids Chemical class 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• BMHFDRGHQVIYHY-SMDDNHRTSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C1CN[C@@H](C)C[C@]11N(C=2C=C(F)C=CC=2)S(=O)(=O)N(C)C1 BMHFDRGHQVIYHY-SMDDNHRTSA-N 0.000 description 5
• CYKZAXPPHLTJOC-NKUHCKNESA-N (7s)-1-(3-fluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C1CN[C@@H](C)CC11N(C=2C=C(F)C=CC=2)S(=O)(=O)NC1 CYKZAXPPHLTJOC-NKUHCKNESA-N 0.000 description 5
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
• 239000002168 alkylating agent Substances 0.000 description 5
• 229940100198 alkylating agent Drugs 0.000 description 5
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 5
• 235000005985 organic acids Nutrition 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 235000015320 potassium carbonate Nutrition 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 5
• 239000011541 reaction mixture Substances 0.000 description 5
• 238000006268 reductive amination reaction Methods 0.000 description 5
• 201000000980 schizophrenia Diseases 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 239000007921 spray Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• CWGAHWNAPIPZCT-GKIFFHSXSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-3-(5-phenyl-4,5-dihydro-1,2-oxazol-3-yl)-8-[(3-propan-2-yloxyphenyl)methyl]-2$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(C=4CC(ON=4)C=4C=CC=CC=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 CWGAHWNAPIPZCT-GKIFFHSXSA-N 0.000 description 4
• UFOREQIFXQCGQT-MGPUTAFESA-N (5r,7s)-1-(3-fluorophenyl)-8-[(3-iodophenyl)methyl]-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2C=C(I)C=CC=2)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 UFOREQIFXQCGQT-MGPUTAFESA-N 0.000 description 4
• YRAJNWYBUCUFBD-UHFFFAOYSA-N 2,2,6,6-tetramethylheptane-3,5-dione Chemical compound CC(C)(C)C(=O)CC(=O)C(C)(C)C YRAJNWYBUCUFBD-UHFFFAOYSA-N 0.000 description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 4
• 208000020925 Bipolar disease Diseases 0.000 description 4
• 208000028698 Cognitive impairment Diseases 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 208000019695 Migraine disease Diseases 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 4
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 4
• RVDIMCUGAKSXAL-BJQOMGFOSA-N benzyl (7s)-1-(3-fluorophenyl)-7-methyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound C([C@@H](N(CC1)C(=O)OCC=2C=CC=CC=2)C)C21CNS(=O)(=O)N2C1=CC=CC(F)=C1 RVDIMCUGAKSXAL-BJQOMGFOSA-N 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 230000002490 cerebral effect Effects 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• 125000000842 isoxazolyl group Chemical group 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 206010027599 migraine Diseases 0.000 description 4
• 230000036407 pain Effects 0.000 description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 125000003226 pyrazolyl group Chemical group 0.000 description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 description 4
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 125000003831 tetrazolyl group Chemical group 0.000 description 4
• 125000000335 thiazolyl group Chemical group 0.000 description 4
• 125000001425 triazolyl group Chemical group 0.000 description 4
• 208000037259 Amyloid Plaque Diseases 0.000 description 3
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 3
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 3
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• 201000010374 Down Syndrome Diseases 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 3
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 238000006069 Suzuki reaction reaction Methods 0.000 description 3
• 206010044688 Trisomy 21 Diseases 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
• RVDIMCUGAKSXAL-HRAATJIYSA-N benzyl (5r,7s)-1-(3-fluorophenyl)-7-methyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound C([C@@]12C[C@@H](N(CC2)C(=O)OCC=2C=CC=CC=2)C)NS(=O)(=O)N1C1=CC=CC(F)=C1 RVDIMCUGAKSXAL-HRAATJIYSA-N 0.000 description 3
• 238000004296 chiral HPLC Methods 0.000 description 3
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 3
• 101150047356 dec-1 gene Proteins 0.000 description 3
• 238000001212 derivatisation Methods 0.000 description 3
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 3
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 3
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
• 125000001786 isothiazolyl group Chemical group 0.000 description 3
• 238000001819 mass spectrum Methods 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 230000035772 mutation Effects 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 description 3
• 125000002971 oxazolyl group Chemical group 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 3
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
• 125000002098 pyridazinyl group Chemical group 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 238000003756 stirring Methods 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 238000003419 tautomerization reaction Methods 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 238000011200 topical administration Methods 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
• 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
• 229910052721 tungsten Inorganic materials 0.000 description 3
• 229910052727 yttrium Inorganic materials 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
• MESBEJMKDIGUIE-TVQRCGJNSA-N (5r,7s)-1-(3,5-difluorophenyl)-7-methyl-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C1CN[C@@H](C)C[C@]11N(C=2C=C(F)C=C(F)C=2)S(=O)(=O)NC1 MESBEJMKDIGUIE-TVQRCGJNSA-N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 2
• QMWYDZLBWGJQOY-UHFFFAOYSA-N 1,3,8-triazaspiro[4.5]decane Chemical compound N1CNCC11CCNCC1 QMWYDZLBWGJQOY-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• WNPFDMGMNSMOMD-UHFFFAOYSA-M 1-imidazol-1-ylsulfonyl-3-methylimidazol-3-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=[N+](C)C=CN1S(=O)(=O)N1C=NC=C1 WNPFDMGMNSMOMD-UHFFFAOYSA-M 0.000 description 2
• NFIDBGJMFKNGGQ-UHFFFAOYSA-N 2-(2-methylpropyl)phenol Chemical compound CC(C)CC1=CC=CC=C1O NFIDBGJMFKNGGQ-UHFFFAOYSA-N 0.000 description 2
• PGJXFACHLLIKFG-UHFFFAOYSA-N 2-methyl-6-phenylphenol Chemical compound CC1=CC=CC(C=2C=CC=CC=2)=C1O PGJXFACHLLIKFG-UHFFFAOYSA-N 0.000 description 2
• QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 2
• IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
• PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 description 2
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• 102000009091 Amyloidogenic Proteins Human genes 0.000 description 2
• 108010048112 Amyloidogenic Proteins Proteins 0.000 description 2
• 206010059245 Angiopathy Diseases 0.000 description 2
• 208000019901 Anxiety disease Diseases 0.000 description 2
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 201000006062 Asperger syndrome Diseases 0.000 description 2
• 206010003805 Autism Diseases 0.000 description 2
• 208000020706 Autistic disease Diseases 0.000 description 2
• 229910015845 BBr3 Inorganic materials 0.000 description 2
• 101710150192 Beta-secretase 1 Proteins 0.000 description 2
• 201000006474 Brain Ischemia Diseases 0.000 description 2
• 206010048962 Brain oedema Diseases 0.000 description 2
• 206010008120 Cerebral ischaemia Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000000094 Chronic Pain Diseases 0.000 description 2
• 208000027691 Conduct disease Diseases 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
• 206010011878 Deafness Diseases 0.000 description 2
• 208000031124 Dementia Alzheimer type Diseases 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 208000011688 Generalised anxiety disease Diseases 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 239000007818 Grignard reagent Substances 0.000 description 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• 206010019196 Head injury Diseases 0.000 description 2
• 208000010496 Heart Arrest Diseases 0.000 description 2
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• 208000004404 Intractable Pain Diseases 0.000 description 2
• 206010026749 Mania Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 208000019022 Mood disease Diseases 0.000 description 2
• 208000008238 Muscle Spasticity Diseases 0.000 description 2
• 208000021642 Muscular disease Diseases 0.000 description 2
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 2
• 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• 208000037273 Pathologic Processes Diseases 0.000 description 2
• 229940049937 Pgp inhibitor Drugs 0.000 description 2
• 206010065016 Post-traumatic pain Diseases 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• 239000007868 Raney catalyst Substances 0.000 description 2
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• 206010041250 Social phobia Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 208000005392 Spasm Diseases 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
• 206010043118 Tardive Dyskinesia Diseases 0.000 description 2
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• 208000009205 Tinnitus Diseases 0.000 description 2
• 206010044565 Tremor Diseases 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 206010046543 Urinary incontinence Diseases 0.000 description 2
• 201000004810 Vascular dementia Diseases 0.000 description 2
• 206010047700 Vomiting Diseases 0.000 description 2
• 208000005298 acute pain Diseases 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical group C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
• RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 229960004372 aripiprazole Drugs 0.000 description 2
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
• 229940049706 benzodiazepine Drugs 0.000 description 2
• 150000001557 benzodiazepines Chemical class 0.000 description 2
• 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 2
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 2
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 2
• MTYDOWZLPPHCPC-BJQOMGFOSA-N benzyl (2s)-4-(aminomethyl)-4-(3-fluoroanilino)-2-methylpiperidine-1-carboxylate Chemical compound C([C@@H]1C)C(CN)(NC=2C=C(F)C=CC=2)CCN1C(=O)OCC1=CC=CC=C1 MTYDOWZLPPHCPC-BJQOMGFOSA-N 0.000 description 2
• KTEGGOXSIVMIRM-BJQOMGFOSA-N benzyl (2s)-4-cyano-4-(3-fluoroanilino)-2-methylpiperidine-1-carboxylate Chemical compound C([C@@H]1C)C(C#N)(NC=2C=C(F)C=CC=2)CCN1C(=O)OCC1=CC=CC=C1 KTEGGOXSIVMIRM-BJQOMGFOSA-N 0.000 description 2
• JBDLSOBXWILEQE-WTYVLRPYSA-N benzyl (2s,4r)-4-(3-fluoroanilino)-4-[[(2-hydroxy-3-methoxyphenoxy)sulfonylamino]methyl]-2-methylpiperidine-1-carboxylate Chemical compound COC1=CC=CC(OS(=O)(=O)NC[C@@]2(C[C@H](C)N(CC2)C(=O)OCC=2C=CC=CC=2)NC=2C=C(F)C=CC=2)=C1O JBDLSOBXWILEQE-WTYVLRPYSA-N 0.000 description 2
• SRBPTEWVLVELLD-HTAPYJJXSA-N benzyl (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane-8-carboxylate Chemical compound C([C@@]12C[C@@H](N(CC2)C(=O)OCC=2C=CC=CC=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 SRBPTEWVLVELLD-HTAPYJJXSA-N 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 208000006752 brain edema Diseases 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 230000000747 cardiac effect Effects 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 206010008118 cerebral infarction Diseases 0.000 description 2
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 229960004170 clozapine Drugs 0.000 description 2
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
• 238000011260 co-administration Methods 0.000 description 2
• 229960003920 cocaine Drugs 0.000 description 2
• 230000036461 convulsion Effects 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000006735 deficit Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 2
• 229960003530 donepezil Drugs 0.000 description 2
• 206010015037 epilepsy Diseases 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 125000003838 furazanyl group Chemical group 0.000 description 2
• 229960003980 galantamine Drugs 0.000 description 2
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
• 208000029364 generalized anxiety disease Diseases 0.000 description 2
• 239000002748 glycoprotein P inhibitor Substances 0.000 description 2
• 150000004795 grignard reagents Chemical class 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 230000010370 hearing loss Effects 0.000 description 2
• 231100000888 hearing loss Toxicity 0.000 description 2
• 208000016354 hearing loss disease Diseases 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 239000003326 hypnotic agent Substances 0.000 description 2
• 230000000147 hypnotic effect Effects 0.000 description 2
• 230000002218 hypoglycaemic effect Effects 0.000 description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 description 2
• 125000002636 imidazolinyl group Chemical group 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 2
• 125000005990 isobenzothienyl group Chemical group 0.000 description 2
• 125000005438 isoindazolyl group Chemical group 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 229960003194 meglumine Drugs 0.000 description 2
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
• 229960004640 memantine Drugs 0.000 description 2
• 206010027175 memory impairment Diseases 0.000 description 2
• 208000027061 mild cognitive impairment Diseases 0.000 description 2
• 230000003387 muscular Effects 0.000 description 2
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
• 201000003631 narcolepsy Diseases 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
• 230000000626 neurodegenerative effect Effects 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 230000003961 neuronal insult Effects 0.000 description 2
• 208000021722 neuropathic pain Diseases 0.000 description 2
• 229960002715 nicotine Drugs 0.000 description 2
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
• 150000002825 nitriles Chemical class 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 229960005017 olanzapine Drugs 0.000 description 2
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
• 229940127240 opiate Drugs 0.000 description 2
• 229960001057 paliperidone Drugs 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 208000019906 panic disease Diseases 0.000 description 2
• 230000009054 pathological process Effects 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 208000033300 perinatal asphyxia Diseases 0.000 description 2
• 235000019271 petrolatum Nutrition 0.000 description 2
• 239000008363 phosphate buffer Substances 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 208000028173 post-traumatic stress disease Diseases 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 239000003380 propellant Substances 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
• 125000002755 pyrazolinyl group Chemical group 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• MZPWKJZDOCIALD-UHFFFAOYSA-N pyrocatechol sulfate Chemical compound OC1=CC=CC=C1OS(O)(=O)=O MZPWKJZDOCIALD-UHFFFAOYSA-N 0.000 description 2
• 229960004431 quetiapine Drugs 0.000 description 2
• URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
• 229960001534 risperidone Drugs 0.000 description 2
• RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 2
• 229940125723 sedative agent Drugs 0.000 description 2
• 239000000932 sedative agent Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 208000019116 sleep disease Diseases 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 208000018198 spasticity Diseases 0.000 description 2
• 210000000278 spinal cord Anatomy 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 238000010189 synthetic method Methods 0.000 description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 231100000886 tinnitus Toxicity 0.000 description 2
• 235000019505 tobacco product Nutrition 0.000 description 2
• 230000000699 topical effect Effects 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
• 230000008733 trauma Effects 0.000 description 2
• 125000004306 triazinyl group Chemical group 0.000 description 2
• 125000004950 trifluoroalkyl group Chemical group 0.000 description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 description 2
• 229960000281 trometamol Drugs 0.000 description 2
• 229910052720 vanadium Inorganic materials 0.000 description 2
• 235000012431 wafers Nutrition 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
• 229960000607 ziprasidone Drugs 0.000 description 2
• MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• OFDARGFSZLIHQQ-SIKLNZKXSA-N (5r,7s)-1-(3-fluoro-4-methylphenyl)-3,7-dimethyl-8-[(1-propan-2-yloxycyclobutyl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound N1([C@H](C[C@]2(N(S(=O)(=O)N(C)C2)C=2C=C(F)C(C)=CC=2)CC1)C)CC1(OC(C)C)CCC1 OFDARGFSZLIHQQ-SIKLNZKXSA-N 0.000 description 1
• CVPXZTQJPHYLAQ-YADARESESA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[(3-propan-2-yloxyphenyl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 CVPXZTQJPHYLAQ-YADARESESA-N 0.000 description 1
• PAYUPVYKZAFKBN-KSFYIVLOSA-N (5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-8-[[4-(oxetan-3-ylmethyl)-1,3-thiazol-5-yl]methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound C([C@@]12C[C@@H](N(CC2)CC2=C(N=CS2)CC2COC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 PAYUPVYKZAFKBN-KSFYIVLOSA-N 0.000 description 1
• MTXHYMVFEGQFPT-HTAPYJJXSA-N (5r,7s)-1-(3-fluorophenyl)-7-methyl-8-[(6-propan-2-yloxypyridin-2-yl)methyl]-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide Chemical compound CC(C)OC1=CC=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)NC3)C=3C=C(F)C=CC=3)CC2)C)=N1 MTXHYMVFEGQFPT-HTAPYJJXSA-N 0.000 description 1
• JISWKJZPVUHQEI-KSFYIVLOSA-N (5r,7s)-8-[(4-cyclobutyloxy-1,3-thiazol-5-yl)methyl]-1-(3-fluorophenyl)-3,7-dimethyl-2$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)OC2CCC2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 JISWKJZPVUHQEI-KSFYIVLOSA-N 0.000 description 1
• CYNJHNQWUQFBEA-MBSDFSHPSA-N (5s,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-MBSDFSHPSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
• SHTKKEZYEHSFEO-UHFFFAOYSA-N 1,3-diazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraene Chemical compound C1CCCN2C=NC3=CC=CC1=C23 SHTKKEZYEHSFEO-UHFFFAOYSA-N 0.000 description 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
• HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 description 1
• JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 description 1
• KDDVZGFLGMXKRC-UHFFFAOYSA-N 1-(bromomethyl)-3-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC(CBr)=C1 KDDVZGFLGMXKRC-UHFFFAOYSA-N 0.000 description 1
• AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
• 125000006083 1-bromoethyl group Chemical group 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• 238000004791 1D NOESY Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 1
• ICFGFAUMBISMLR-UHFFFAOYSA-N 1h-pyrazole-5-carbaldehyde Chemical compound O=CC=1C=CNN=1 ICFGFAUMBISMLR-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
• XUVWQPHDYOOCMD-UHFFFAOYSA-N 2,4-diazatricyclo[5.3.1.04,11]undeca-1(10),2,7(11),8-tetraene Chemical compound C1=NC2=CC=CC3=C2N1CC3 XUVWQPHDYOOCMD-UHFFFAOYSA-N 0.000 description 1
• JQDNCGRNPYKRAO-UHFFFAOYSA-N 2-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=CC=N1 JQDNCGRNPYKRAO-UHFFFAOYSA-N 0.000 description 1
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
• DHJFONFHJYXGEV-ORAYPTAESA-N 2-[[(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-(trifluoromethoxy)pyrimidin-5-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=C(OC(F)(F)F)C(O)=CN=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 DHJFONFHJYXGEV-ORAYPTAESA-N 0.000 description 1
• VBGBZIYSKYSDFL-ORAYPTAESA-N 2-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(trifluoromethyl)pyrimidin-5-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=C(C(O)=CN=2)C(F)(F)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 VBGBZIYSKYSDFL-ORAYPTAESA-N 0.000 description 1
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
• FWTQCPRPCOHXPK-QMHKHESXSA-N 2-cyclopropyloxy-6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=C(OC3CC3)C(O)=CC=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 FWTQCPRPCOHXPK-QMHKHESXSA-N 0.000 description 1
• ZNCUUYCDKVNVJH-UHFFFAOYSA-N 2-isopropoxyphenol Chemical compound CC(C)OC1=CC=CC=C1O ZNCUUYCDKVNVJH-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• IFZZDINNCWFGEO-UHFFFAOYSA-N 2-propan-2-yloxypyridine Chemical compound CC(C)OC1=CC=CC=N1 IFZZDINNCWFGEO-UHFFFAOYSA-N 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• LFZCNPNMQPPMRK-UHFFFAOYSA-N 24246-26-2 Chemical compound C1CCC2=CC=CC3=C2N1C=N3 LFZCNPNMQPPMRK-UHFFFAOYSA-N 0.000 description 1
• 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• MOLKLIYWXFEEJM-UHFFFAOYSA-N 2h-triazole-4-carbaldehyde Chemical compound O=CC1=CNN=N1 MOLKLIYWXFEEJM-UHFFFAOYSA-N 0.000 description 1
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
• KQOIBXZRCYFZSO-UHFFFAOYSA-N 3,5-difluoroaniline Chemical compound NC1=CC(F)=CC(F)=C1 KQOIBXZRCYFZSO-UHFFFAOYSA-N 0.000 description 1
• QQCLMRHDATZXIO-QDOBKRIMSA-N 3-[(5r,7s)-3,7-dimethyl-8-[(2-methylcyclobutyl)methyl]-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-1-yl]-5-fluoropyridine-2-carbonitrile Chemical compound CC1CCC1CN1[C@@H](C)C[C@]2(N(S(=O)(=O)N(C)C2)C=2C(=NC=C(F)C=2)C#N)CC1 QQCLMRHDATZXIO-QDOBKRIMSA-N 0.000 description 1
• LNXKJBBQEFYTQV-UHFFFAOYSA-N 3-bromo-5-phenyl-4,5-dihydro-1,2-oxazole Chemical compound C1C(Br)=NOC1C1=CC=CC=C1 LNXKJBBQEFYTQV-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• OOGOFUKAJDPHDJ-UHFFFAOYSA-N 3-fluoro-4-hydroxy-5-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(F)=C1O OOGOFUKAJDPHDJ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• NOBKCEXLDDGYID-UHFFFAOYSA-N 3-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC=CC(C=O)=C1 NOBKCEXLDDGYID-UHFFFAOYSA-N 0.000 description 1
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• WHFLTORLWBHUJN-HFJWLAOPSA-N 4-(2-chlorophenyl)-6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C=2C(=CC=CC=2)Cl)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 WHFLTORLWBHUJN-HFJWLAOPSA-N 0.000 description 1
• MCQWSAJFQHKZOP-HFJWLAOPSA-N 4-(2-fluorophenyl)-6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C=2C(=CC=CC=2)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 MCQWSAJFQHKZOP-HFJWLAOPSA-N 0.000 description 1
• OFLZAVKYXKUOTN-UPCLLVRISA-N 4-(5-chlorothiophen-2-yl)-6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=3SC(Cl)=CC=3)C=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 OFLZAVKYXKUOTN-UPCLLVRISA-N 0.000 description 1
• WPBHJFDUQLUDGD-GAJHUEQPSA-N 4-[[(5r,7s)-1-(1,3-dimethylpyrazol-4-yl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C(=NN(C)C=3)C)CC2)C)=C1 WPBHJFDUQLUDGD-GAJHUEQPSA-N 0.000 description 1
• PFJXMIHWRXIUSR-BXKMTCNYSA-N 4-[[(5r,7s)-1-(3,4-difluorophenyl)-3,7-dimethyl-2,2-dioxo-2$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(F)=CC=3)CC2)C)=C1 PFJXMIHWRXIUSR-BXKMTCNYSA-N 0.000 description 1
• MQZUDGCBCBUMLX-GAJHUEQPSA-N 4-[[(5r,7s)-1-(3-ethyl-1,2-oxazol-4-yl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound CCC1=NOC=C1N1S(=O)(=O)N(C)C[C@]21C[C@H](C)N(CC=1C=C(OC(C)C)C(O)=CC=1)CC2 MQZUDGCBCBUMLX-GAJHUEQPSA-N 0.000 description 1
• RGOUGEKOMAEETC-AFMDSPMNSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-7-methyl-2,2-dioxo-3-(1,3-thiazol-2-yl)-2$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=4SC=CN=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 RGOUGEKOMAEETC-AFMDSPMNSA-N 0.000 description 1
• XPPOIAXKZPNLCP-AFMDSPMNSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-7-methyl-3-(1,2-oxazol-4-yl)-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C4=CON=C4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 XPPOIAXKZPNLCP-AFMDSPMNSA-N 0.000 description 1
• MOTVEVXNVLRPFB-AFMDSPMNSA-N 4-[[(5r,7s)-1-(3-fluorophenyl)-7-methyl-3-(1,3-oxazol-2-yl)-2,2-dioxo-2$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=4OC=CN=4)C3)C=3C=C(F)C=CC=3)CC2)C)=C1 MOTVEVXNVLRPFB-AFMDSPMNSA-N 0.000 description 1
• BDNXFSUFWRPKFU-BXKMTCNYSA-N 4-[[(5r,7s)-1-(5-fluoro-6-methylpyridin-3-yl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C=3C=C(F)C(C)=NC=3)CC2)C)=C1 BDNXFSUFWRPKFU-BXKMTCNYSA-N 0.000 description 1
• CHGFZOILZQVYJS-BXKMTCNYSA-N 4-[[(5r,7s)-1-[5-fluoro-2-(2,2,2-trifluoroethylamino)pyridin-3-yl]-3,7-dimethyl-2,2-dioxo-2$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(=NC=C(F)C=3)NCC(F)(F)F)CC2)C)=C1 CHGFZOILZQVYJS-BXKMTCNYSA-N 0.000 description 1
• ZDOFAMHUFNDYHB-KSFYIVLOSA-N 4-[[(5r,7s)-3,7-dimethyl-1-(5-methyl-1,3-thiazol-4-yl)-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-propan-2-yloxyphenol Chemical compound C1=C(O)C(OC(C)C)=CC(CN2[C@H](C[C@]3(N(S(=O)(=O)N(C)C3)C3=C(SC=N3)C)CC2)C)=C1 ZDOFAMHUFNDYHB-KSFYIVLOSA-N 0.000 description 1
• HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
• BKHMVYFYHYQLPH-OYHNWAKOSA-N 4-cyclopropyloxy-2-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyrimidin-5-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=C(OC3CC3)C(O)=CN=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 BKHMVYFYHYQLPH-OYHNWAKOSA-N 0.000 description 1
• JMQFIZKKAOGNHT-QMHKHESXSA-N 4-cyclopropyloxy-6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(OC3CC3)C=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 JMQFIZKKAOGNHT-QMHKHESXSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• TWSIYGATPWEKBK-UHFFFAOYSA-N 4h-1,3-benzodioxine Chemical compound C1=CC=C2OCOCC2=C1 TWSIYGATPWEKBK-UHFFFAOYSA-N 0.000 description 1
• QAHCQGXGAYRHHW-UHFFFAOYSA-N 5-bromo-2,3-difluorophenol Chemical compound OC1=CC(Br)=CC(F)=C1F QAHCQGXGAYRHHW-UHFFFAOYSA-N 0.000 description 1
• WRSPJAHKGRZXMS-UHFFFAOYSA-N 5-methoxy-1,3,2$l^{6}-benzodioxathiole 2,2-dioxide Chemical compound COC1=CC=C2OS(=O)(=O)OC2=C1 WRSPJAHKGRZXMS-UHFFFAOYSA-N 0.000 description 1
• DFZGHONGFLATSY-UHFFFAOYSA-N 6-(hydroxymethyl)-3-phenylmethoxy-3h-pyridin-4-one Chemical compound C1=NC(CO)=CC(=O)C1OCC1=CC=CC=C1 DFZGHONGFLATSY-UHFFFAOYSA-N 0.000 description 1
• ZVYICOUSCDLTBT-AFMDSPMNSA-N 6-[[(5R,7S)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2lambda6-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(3-methylpyridin-2-yl)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C=2C(=CC=CN=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZVYICOUSCDLTBT-AFMDSPMNSA-N 0.000 description 1
• CWDVOXSHJMJRLV-VBKZILBWSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-2-(trifluoromethoxy)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=C(OC(F)(F)F)C(O)=CC=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 CWDVOXSHJMJRLV-VBKZILBWSA-N 0.000 description 1
• VWWHCVQJWLRCLT-CCLHPLFOSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(2-methylphenyl)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C=2C(=CC=CC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 VWWHCVQJWLRCLT-CCLHPLFOSA-N 0.000 description 1
• FHFNFBWLIQRUPY-AVRWGWEMSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(3-methylthiophen-2-yl)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C3=C(C=CS3)C)C=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 FHFNFBWLIQRUPY-AVRWGWEMSA-N 0.000 description 1
• FZMVROJUMOEGCH-AFMDSPMNSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(4-methylpyridin-3-yl)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C=2C(=CC=NC=2)C)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 FZMVROJUMOEGCH-AFMDSPMNSA-N 0.000 description 1
• ZBNTXBXNKAIFDM-VBKZILBWSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(trifluoromethoxy)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(OC(F)(F)F)C=2)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 ZBNTXBXNKAIFDM-VBKZILBWSA-N 0.000 description 1
• NTVNMNSMYXAFEG-VBKZILBWSA-N 6-[[(5r,7s)-1-(3-fluorophenyl)-3,7-dimethyl-2,2-dioxo-2$l^{6}-thia-1,3,8-triazaspiro[4.5]decan-8-yl]methyl]-4-(trifluoromethyl)pyridin-3-ol Chemical compound C([C@@]12C[C@@H](N(CC2)CC=2N=CC(O)=C(C=2)C(F)(F)F)C)N(C)S(=O)(=O)N1C1=CC=CC(F)=C1 NTVNMNSMYXAFEG-VBKZILBWSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 208000018282 ACys amyloidosis Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 229940126077 BACE inhibitor Drugs 0.000 description 1
• 0 BN([C@]1(C[C@@](*)N(*)CC1)C(*)(*)N1*)S1(=O)=O Chemical compound BN([C@]1(C[C@@](*)N(*)CC1)C(*)(*)N1*)S1(=O)=O 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 229920001661 Chitosan Polymers 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 1
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
• 208000003311 Cytochrome P-450 Enzyme Inhibitors Diseases 0.000 description 1
• 229940122280 Cytochrome P450 inhibitor Drugs 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 241000283953 Lagomorpha Species 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 101000931108 Mus musculus DNA (cytosine-5)-methyltransferase 1 Proteins 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• 229910014299 N-Si Inorganic materials 0.000 description 1
• 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 102000029797 Prion Human genes 0.000 description 1
• 108091000054 Prion Proteins 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 101800000130 Soluble APP-beta Proteins 0.000 description 1
• 102400000576 Soluble APP-beta Human genes 0.000 description 1
• 238000007059 Strecker synthesis reaction Methods 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000003172 aldehyde group Chemical group 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000003942 amyloidogenic effect Effects 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000011948 assay development Methods 0.000 description 1
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
• 125000004599 benzpyrazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• NKUKIRSAMUEXPP-NSHDSACASA-N benzyl (2s)-2-methyl-4-oxopiperidine-1-carboxylate Chemical compound C[C@H]1CC(=O)CCN1C(=O)OCC1=CC=CC=C1 NKUKIRSAMUEXPP-NSHDSACASA-N 0.000 description 1
• MTYDOWZLPPHCPC-HRAATJIYSA-N benzyl (2s,4r)-4-(aminomethyl)-4-(3-fluoroanilino)-2-methylpiperidine-1-carboxylate Chemical compound C([C@](CN)(C[C@@H]1C)NC=2C=C(F)C=CC=2)CN1C(=O)OCC1=CC=CC=C1 MTYDOWZLPPHCPC-HRAATJIYSA-N 0.000 description 1
• KTEGGOXSIVMIRM-HRAATJIYSA-N benzyl (2s,4r)-4-cyano-4-(3-fluoroanilino)-2-methylpiperidine-1-carboxylate Chemical compound C([C@](C[C@@H]1C)(NC=2C=C(F)C=CC=2)C#N)CN1C(=O)OCC1=CC=CC=C1 KTEGGOXSIVMIRM-HRAATJIYSA-N 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 239000000227 bioadhesive Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000005586 carbonic acid group Chemical group 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 239000003636 conditioned culture medium Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
• 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000006264 debenzylation reaction Methods 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• UOQACRNTVQWTFF-UHFFFAOYSA-N decane-1,10-dithiol Chemical compound SCCCCCCCCCCS UOQACRNTVQWTFF-UHFFFAOYSA-N 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
• JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229950010286 diolamine Drugs 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 125000005883 dithianyl group Chemical group 0.000 description 1
• 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 238000010410 dusting Methods 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 239000010408 film Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• PUPFATUGTIQBQA-UZQPLGKSSA-N fluorophen Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@H]2[C@@H]1C)CN2CCC1=CC=C(F)C=C1 PUPFATUGTIQBQA-UZQPLGKSSA-N 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 102000044297 human BACE1 Human genes 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 150000002429 hydrazines Chemical class 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000007915 intraurethral administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 238000007914 intraventricular administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000005969 isothiazolinyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000003514 metabotropic receptor agonist Substances 0.000 description 1
• CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical group [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
• GHNGBFHLUOJHKP-UHFFFAOYSA-N methyl 3-iodo-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(I)=C1 GHNGBFHLUOJHKP-UHFFFAOYSA-N 0.000 description 1
• KJJSHOHQQHACLE-UHFFFAOYSA-N methyl 5-hydroxypyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(O)=C1 KJJSHOHQQHACLE-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• YKFLJYAKACCWMH-UHFFFAOYSA-N methyl piperidine-1-carboxylate Chemical compound COC(=O)N1CCCCC1 YKFLJYAKACCWMH-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000003595 mist Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 230000036457 multidrug resistance Effects 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 239000002353 niosome Substances 0.000 description 1
• 125000002560 nitrile group Chemical group 0.000 description 1
• VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229950004864 olamine Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000013110 organic ligand Substances 0.000 description 1
• 125000005880 oxathiolanyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000003551 oxepanyl group Chemical group 0.000 description 1
• 125000003585 oxepinyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 125000003544 oxime group Chemical group 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
• 125000001828 phenalenyl group Chemical group C1(C=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 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 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical group [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000009790 rate-determining step (RDS) Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 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
• 230000003248 secreting effect Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229960001367 tartaric acid Drugs 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
• 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
• 238000012360 testing method Methods 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000001583 thiepanyl group Chemical group 0.000 description 1
• 125000003777 thiepinyl group Chemical group 0.000 description 1
• 125000002053 thietanyl group Chemical group 0.000 description 1
• 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
• 125000001806 thionaphthenyl group Chemical group 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1