Phosphodiesterase inhibitors and uses thereof

摘要

The invention provides for compounds that are phosphodiesterase inhibitors. The invention further provides for a method for screening compounds that bind to and modulate a phosphosdiesterase protein. The invention also provides methods for treating conditions associated with accumulated amyloid-beta peptide deposit accumulations by administering a phosphodiesterase-binding compound to a subject.

主权项

1. A method for treating a subject afflicted with Alzheimer's disease, Lewy body dementia, inclusion body myositis, or cerebral amyloid angiopathy, the method comprising:
administering to the subject an effective amount of a composition comprising a PDE5 inhibitor compound of Formula (V): wherein:
A is O or N;X is —(CH2)n, C(O), S(O), or S(O)2;R1 is C3-C8 cycloalkyl, —NR7R8, or —SR7;R2 is —CH2OR6 or —CO2R8;R3 is hydrogen or halogen;R4 is —CN or halogen;R5 is hydrogen or —OR6;R6 is hydrogen, —C1-C6 alkyl, —C3-C8 cycloalkyl, or —C(O)R9;R7 and R8 are each independently hydrogen, —C1-C6 alkyl, —C3-C8 cycloalkyl, or —C(O)R9, wherein the C1-C6 alkyl or C3-C8 cycloalkyl are optionally substituted with —C1-C6 alkyl, —C3-C8 cycloalkyl, —NR9R10, —SR9, or heterocyclyl; or, R7 and R8 together with the nitrogen atom to which they are attached form a 3 to 8-membered heterocycle, wherein any one of the ring carbon atoms is optionally replaced with a heteroatom, and wherein the heterocycle is optionally substituted with C1-C6 alkyl; andR9 and R10 are each independently hydrogen, C1-C6 alkyl, or C3-C8 cycloalkyl; and n is 1, 2, or 3,or a pharmaceutically acceptable salt or tautomer thereof.