PHENYLMETHYL HEXANAMIDES, AND THE USE THEREOF

摘要

The present invention is to compounds of formula (I) or formula (II) or pharmaceutically acceptable salts thereof for the treatment of PKC-mediated disease states, wherein inter alia R1 is hydrogen, lower alkyl or optionally substituted aryl; R2 is hydrogen or lower alkyl; R3 is hydrogen or -(CH¿2)kR?6, wherein R6 is -CO¿2R?7, -NHC(O)R?7, -NR7R8¿, or -C(O)NR7R8, wherein R?7 and R8¿, independently from one another, are hydrogen, or alkyl provided that when R6 is -CO¿2R?7, R7 is not hydrogen; R?4 and R5¿, independently from one another, are hydrogen or lower alkyl, or wherein R?4 and R5¿, together with the nitrogen to which they are bound, form a saturated or unsaturated 5-, 6-, or 7-membered ring; E is CH-R9, wherein R9 is hydrogen, alkoxy, -OH or -NR10R11, wherein R?10 and R11¿, independently from one another, are hydrogen or lower alkyl, or wherein R?10 and R11¿, together with the nitrogen to which they are bound, form a saturated or unsaturated 5-, 6-, or 7-membered ring; X is CH or N; Y is -CH¿2? or -O, and further wherein Y is positioned on the central aromatic ring either ortho, meta or para relative to the amine containing side chain; Z is -CH2 or optionally substituted aryl; k is an integer between 0 and 10; m is an integer between 0 and 10, provided that m is 0 only when Z is optionally substituted aryl or optionally substituted heteroaryl, and further, provided that when m is 0 and Z is optionally substituted aryl or optionally substituted heteroaryl, R?4 and R5¿ are not hydrogen or lower alkyl; n is an integer between 6 and 20; and p is an integer between 0 and 1, provided that p must be 0 when Z is optionally substituted aryl or optionally substituted heteroaryl.