Fused pyrimidines as inhibitors of p97 complex

Abstract

Disclosed are fused pyrimidine compounds having scaffolds composed of left and right rings, the left ring being a saturated carbocyclic or heterocyclic ring and the right ring being a pyrimidine ring. The left saturated ring is fused to the pyrimidine ring at the 5 and 6 carbons of the pyrimidine. The saturated ring may be 5 or 6 members in size and may be all carbon or may contain a single oxygen, sulfur or nitrogen atom as one of the non-fused members of the ring. The pyrimidine ring is substituted at the two position by a 5:6 bicyclic aromatic heterocycle such as indole, benzimidazole or benzopyrazole and at the four position by an aryl methyl amino group. The 5:6 bicyclic aromatic heterocycle is substituted at its 2 position by hydrogen or an aliphatic or functional aliphatic group and at the 4 position by a functional group as described herein. The aryl methyl amino group may be aminobenzyl or aminomethyl-substituted phenyl. These fused pyrimidine compounds are inhibitors of the AAA proteosome complex containing the enzyme complex p97 and are effective medicinal agents for the treatment of diseases associated with p97 bioactivity such as cancer.