8-HYDROCARBYL SUBSTITUTED BENZODIZOCINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS PROTEIN KINASE C (=PKC) MODULATORS

摘要

Compounds of formula (I) wherein R1 is H, (C1-C5)alkyl, OR?a, SRa, N(Ra)(Rb¿), halo, NO¿2?, NHC(O)[(C1-C4)alkyl] or NHOH; R2 is a (C5-C22) hydrocarbyl group, optionally comprising 1-3 double bonds, 1-2 triple bonds or a mixture thereof, or (C6-C12)aryl(C2-C10)alkyl, wherein the alkyl moiety optionally comprises 1-2 double bonds, 1-2 triple bonds or a mixture thereof; wherein said (C5-C22) hydrocarbyl group or said (C6-C12)aryl(C2-C10)alkyl may optionally be substituted with 1 or 2 substituents independently selected from the group consisting of halo, hydroxy, cyano, nitro, (C1-C5)alkyl, (C1-C5)alkoxy, trifluoromethyl, trifluoromethoxy, -C(=O)O(C1-C5)alkyl, and N(R?e)(Rf); R¿1 and R2 together are -CH(Rc)-CH2-C(O)-N(Rd)-, -C(Rc)=CH-C(O)N(Rd)-, -C(Rc)=CH-N(Rd)- or -C(Rc)=CH-O-; R¿3? is H, OH or halo; R?a and Rb¿ are independently H or (C¿1?-C5)alkyl; R?c¿ is a (C¿5?-C22) hydrocarbyl group; R?d¿ is H or (C¿1?-C5)alkyl; R?e and Rf¿ are independently hydrogen, (C¿1?-C5)alkyl, or (C1-C5)alkanoyl, or together with the nitrogen to which they are attached are pyrrolidino, piperidino or morpholino; Z is H or (C1-C5)alkyl, and Y is H or (C1-C5)alkyl; and their pharmaceutically acceptable salts, are PKC modulators and are useful for treating i.e. cancer mammals. Also disclosed are pharmaceutical compositions comprising compounds of formula (I), processes for preparing compounds of formula (I), and intermediates useful for preparing compounds of formula (I).