Nanoscale Neuromodulating Platform for Retina Neuron Activation Apparatus and Method

摘要

The present invention relates to methods and compositions for modulating receptors in postsynaptic neurons of damaged or diseased retinas. The invention also related to methods for using the compositions set forth herein for treatment of diseases of hyperexcitability such as epilepsy.

主权项

1. A compound of formula: and pharmaceutically acceptable salts thereof, wherein R1 and R2 are independently C1-C12 alkyl, halo(C1-C12 alkyl), C2-C12 alkenyl, or C2-C12 alkynyl, each optionally substituted with 1, 2, 3 or 4 substituents selected from halogen, —CN, —NO2, —OR6, —NR62, —CO2R6, —CONR62, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, heteroaryl, and heterocycle, wherein each cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocycle is optionally substituted with 1, 2, 3 or 4 R7; R3 is hydrogen, C1-C6 alkyl, or halo(C1-C6 alkyl); R4 and R5 are independently halogen, —CN, —NO2, C1-C6 alkyl, halo(C1-C6 alkyl), —OR6, —NR62, —CO2R6, or —CONR62; X is —N(R8)—, —N(R8)CH2—, —N(R8)CHR8—, —N(R8)(CHR8)2-5—, or —O—; Y═Z is —N═N— or —C(R8)═C(R8)—; and R9 is hydrogen, —CHR6a, —OR6a, —NR6a2, —CO2R6a, —CONR6a2, —CON(R8)—(CH2)1-6—NR6a2, —N(R8)CO—(CH2)1-6—NR6a2, —CON(R8)—(CH2)1-6—N(R8)COR6a, —N(R8)CO—(CH2)1-6—N(R8)COR6a, —CON(R8)—(CH2)1-6—N(R8)COR10, or —N(R8)CO—(CH2)1-6—N(R8)COR10, wherein R10 is —CH2CH2(OCH2CH2)2-50—N(R8)COR6a; where each R6 independently is hydrogen, C1-C6 alkyl, halo(C1-C6 alkyl), C3-C8 cycloalkyl, aryl, heteroaryl, heterocycle, aryl(C1-C6 alkyl)-, C3-C8cycloalkyl(C1-C6 alkyl)-, aryl(C1-C6 alkyl)-, heteroaryl(C1-C6 alkyl)-, or heterocycle(C1-C6 alkyl)-, wherein each alkyl, cycloalkyl, aryl, heteroaryl, and heterocycle is optionally substituted with 1, 2, 3 or 4 R7, or two R6 with the nitrogen to which they are attached form a heterocycle optionally substituted with 1, 2, 3 or 4 R7; where each Rha independently is hydrogen, C1-C6 alkyl, halo(C1-C6 alkyl), C3-C8 cycloalkyl, aryl, heteroaryl, heterocycle, aryl(C1-C6 alkyl)-, C3-C8cycloalkyl(C1-C6 alkyl)-, aryl(C1-C6 alkyl)-, heteroaryl(C1-C6 alkyl)-, or heterocycle(C1-C6 alkyl)-, wherein each alkyl, cycloalkyl, aryl, heteroaryl, and heterocycle is optionally substituted with 1, 2, 3 or 4 R7, or two R6 with the nitrogen to which they are attached form a heterocycle optionally substituted with 1, 2, 3 or 4 R7; where each R7 independently is halogen, —CN, —NO2, —N3, C1-C6 alkyl, halo(C1-C6 alkyl), C1-C6 alkoxy, amino, C1-C6alkylamino, diC1-C6alkylamino, —CO2H, —COH, —CO2R8, or —CON(R8)2; and where each R8 independently is hydrogen or C1-C6 alkyl.