Preparation of ureidoaryl- and carbamoylaryl-bridged morpholinopyrimidine derivatives for use as mTOR and PI3 kinase inhibitors.

Abstract

Title compds. I [A = (un)substituted 9- to 10-membered heterobicyclic ring or 13-membered heterotricyclic ring; T = O, S, or NR4; X = bond, (un)substituted alkenyl, or alkynyl; Y = (un)substituted aryl or heteroaryl; Z = NH, O, or S; R1, R2, R3, and R4 independently = (un)substituted alkyl, alkoxy, or alkylamine; where at least one of R1 and R2, or R3 and R4, or R2 and R3, or R1 and R4 together with the atoms that they bonded to join to form a ring; R5 = H, (un)substituted alkyl, aryl, heteroaryl, etc.; with provisions], and their pharmaceutically acceptable salts, are prepd. and disclosed as mTOR and PI3 kinase inhibitors. Thus, e.g., II was prepd. by general procedure (procedure given). Select I were evaluated for mTOR and PI3K inhibitory activity, and e.g., II demonstrated IC50 values of 1.500 and 492.000 nM towards mTOR and PI3K-α, resp. [on SciFinder(R)]