Rapamycin Analogues and the Uses Thereof in the Treatment of Neurological Disorders
Method of treatment of neurological disorders or complications due to stroke or head injury through the administration of a pharmaceutical composition including a pharmaceutically acceptable excipient or carrier and a compound of formula I are provided:
1 . A method of treating neurological disorders comprising administering to a subject in need thereof a composition comprising a pharmaceutically acceptable excipient or carrier and a compound of the formula I:
wherein:
R 1 and R 2 are different, independent groups and are selected from the group consisting of OR 3 and N(R 3′ )(R 3″ ); or
R 1 and R 2 are different, are connected through a single bond, and are selected from the group consisting of O and NR 3 ;
R 3 , R 3′ , and R 3″ are independently selected from the group consisting of H, C 1 to C 6 alkyl, C 1 to C 6 substituted alkyl, C 3 to C 8 cycloalkyl, substituted C 3 to C 8 cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
R 4 and R 4′ are:
(a) independently selected from the group consisting of H, OH, O(C 1 to C 6 alkyl), O(substituted C 1 to C 6 alkyl), O(acyl), O(aryl), O(substituted aryl), and halogen; or
(b) taken together to form a double bond to O;
R 5 , R 6 , and R 7 are independently selected from the group consisting of H, OH, and OCH 3 ;
R 8 and R 9 are connected through a single bond and are CH 2 ;
R 15 is selected from the group consisting of C═O, CHOH, and CH 2 ;
n is 1 or 2; or
a pharmaceutically acceptable salt thereof.
2 . The method according to claim 1 , wherein said neurological disorder is selected from Alzheimer's disease; epilepsy; Huntington's Disease; Parkinson's Disease; stroke; spinal cord injury; traumatic brain injury; Lewy body dementia; Pick's disease; Niewmann-Pick disease; amyloid angiopathy; cerebral amyloid angiopathy; systemic amyloidosis; hereditary cerebral hemorrhage with amyloidosis of the Dutch type; inclusion body myositis; mild cognitive impairment; Down's syndrome; amyotrophic lateral sclerosis (ALS); multiple sclerosis; Duchenne dystrophy; Becker muscular dystrophy; Facioscapulohumeral (Landouzy-Dejerine) muscular dystrophy; and limb-girdle muscular dystrophy (LGMD).
3 . A method according to claim 2 wherein the disorder is stroke.
4 . A method of treating complications due to stroke or head trauma comprising administering to a subject in need thereof a composition according to claim 1 .