US2006270729A1PendingUtilityA1
Agents useful for reducing amylioid precursor protein and treating dementia and methods of use thereof
Est. expiryNov 2, 2020(expired)· nominal 20-yr term from priority
Inventors:Nigel H. GreigKaren T. Y. ShawQiang YuHarold W. HollowayTada UtsukiTimothy T. SoncrantDonald K. IngramArnold BrossiAnthony GiordanoGordon PowersDiane DavidsonMichael Sturgess
A61K 31/407C07D 495/04A61K 31/345C07D 487/08C07D 209/38A61K 31/325C07D 487/04A61K 31/382C07D 471/04C07D 209/16C07D 209/36C07D 453/04A61P 25/28C07D 491/04C07D 277/82A61K 31/343A61K 31/403A61K 31/405C07D 209/34A61K 31/381
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Claims
Abstract
The present invention provides compounds and methods of administering compounds to a subject that can reduce βAPP production and that is not toxic in a wide range of dosages. The present invention also provides non-carbamate compounds and methods of administering such compounds to a subject that can reduce βAPP production and that is not toxic in a wide range of dosages. It has been discovered that either the racemic or enantiomerically pure non-carbamate compounds can be used to decrease βAPP production.
Claims
exact text as granted — not AI-modified1 - 92 . (canceled)
93 . A pharmaceutical composition comprising a compound of formula VII,
wherein R 5 is an aralkyl and R 8 is a hydrogen, branched or straight chain C 1 -C 8 alkyl, substituted or unsubstituted aryl, or aralkyl, and a carrier.
94 . The pharmaceutical composition of claim 93 , wherein R 8 is a branched or straight chain C 1 -C 8 alkyl.
95 . The pharmaceutical composition of claim 93 , wherein R 5 is benzyl and R 8 is methyl.
96 . The pharmaceutical composition of claim 93 , wherein R 5 is benzyl and R 8 is hydrogen.
97 . The pharmaceutical composition of claim 93 , wherein the compound is a salt.
98 . A method of inhibiting production of amyloid precursor protein in a mammalian cell, comprising contacting the cell with a composition comprising a carrier and compound comprising formula VII:
wherein R 5 is an aralkyl and R 8 is a hydrogen, branched or straight chain C 1 -C 8 alkyl, substituted or unsubstituted aryl, or aralkyl,
whereby the compound inhibits production of amyloid precursor protein in the cell.
99 . The method of claim 98 , wherein R 5 is benzyl and R 8 is methyl.
100 . The method of claim 98 , wherein R 5 is benzyl and R 8 is hydrogen.
101 . The method of claim 98 , wherein the cell is in vivo.
102 . The method of claim 98 , wherein the cell is a human cell.
103 . The method of claim 98 , wherein the composition is in an oral dosage unit.
104 . The method of claim 98 , wherein the compound inhibits the production of amyloid precursor protein and Aβ 1-40 or Aβ 1-42 .
105 . The method of claim 98 , wherein the compound is a salt.
106 . The method of claim 105 , wherein the salt is a tartrate salt.
107 . A method of inhibiting production of amyloid precursor protein in a mammalian cell, comprising contacting the cell with a compound comprising formula V or VI:
wherein R 8 is hydrogen, branched or straight chain C 1 -C 8 alkyl, substituted or unsubstituted aryl, aralkyl, or CR 9 R 10 OR 11 , where R 9 and R 10 are, independently, hydrogen or alkyl, and R 11 is alkyl;
R 3 is branched or straight chain C 1 -C 4 alkyl, or substituted or unsubstituted aryl;
X and Y are, independently, O, S, C(H)R 4 , or NR 5 , wherein R 4 and R 5 are, independently, hydrogen, oxygen, branched or straight chain C 1 -C 8 alkyl, C 2 -C 8 alkenyl, or C 2 -C 8 alkynyl, aralkyl, or substituted or unsubstituted aryl; and
R 6 is hydrogen; C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, aralkyl, or substituted or unsubstituted aryl, or (CH 2 ) n R 7 , where R 7 is hydroxy, alkoxy, cyano, ester, carboxylic acid, substituted or unsubstituted amino, and n is from 1 to 4,
whereby the compound inhibits production of amyloid precursor protein in the mammalian cell,
with the proviso that when the compound is formula V, X is NCH 3 , and Y is NR 5 , where R 5 is hydrogen, loweralkyl, arylloweralkyl, heteroarylloweralkyl, cycloalkylmethyl, or loweralkenyl methyl, R 3 is not methyl or R 8 is not H or loweralkyl.
108 . The method of claim 107 , wherein the compound is a substantially pure (+)-enantiomer.
109 . The method of claim 107 , wherein the compound comprises a substantially pure (−)-enantiomer.
110 . The method of claim 107 , wherein when the compound comprises formula V, and X and Y are NR 5 .
111 . The method of claim 107 , wherein R 5 is branched or straight chain C 1 -C 8 alkyl.
112 . The method of claim 107 , wherein R 5 is methyl.
113 . The method of claim 107 , wherein the compound comprises formula V, R 3 is methyl and X is NCH 3 .
114 . The method of claim 107 , wherein the compound comprises formula V, R 3 is methyl, X is NCH 3 , and Y is NCH 3 .
115 . The method of claim 107 , wherein the compound comprises formula V, and R 8 is C 1 -C 8 straight chain alkyl.
116 . The method of claim 107 , wherein the compound comprises formula V, and R 8 is methyl.
117 . The method of claim 116 , wherein R 3 is methyl, and Y and X are each NCH 3 .
118 . The method of claim 107 , wherein the cell is in vivo.
119 . The method of claim 107 , wherein the cell is a human cell.
120 . The method of claim 107 , wherein the compound inhibits the production of amyloid precursor protein and Aβ 1-40 or Aβ 1-42 .Cited by (0)
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