Monocyclic pyrimidine/pyridine compounds as inhibitors of P97 complex
AssigneeCleave Biosciences, Inc.
InventorsDavid Wustrow, Han-Jie Zhou
Life of this patent
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Abstract
Monocyclic pyrimidine and pyridine compounds having a benzyl amine substituent at the 4 position and a 5:6 bicyclic heteroaryl substituent at the 2 position of the pyrimidine or pyridine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.
Claims12
A monocyclic pyrimidine compound of Formula IIE, IIK or IIP having a pyrimidine scaffold and a benzimidazole, 1-indole or 3-indole group bound to the P2 position of the scaffold:
- Wherein:
- R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, straight, branched or cyclic alkyl of 1 to 6 carbons, carboxylic acid, carboxyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, N-alkylamino methyl with the alkyl group being straight, branched or cyclic of 1 to 6 carbons, sulfonic acid, sulfonyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, sulfonamide, amine (NH2), mono, di or trialkyl amine with the alkyl being straight, branched or cyclic of 1 to 6 carbons, nitrile, carboxamide, N-alkyl carboxamide of 1 to 6 carbons in the straight, branched or cyclic alkyl group, perfluoroalkyl of 1 to 3 carbons, straight, branched or cyclic alkoxy of 1 to 6 carbons;
- Each R3 is independently selected from the group consisting of hydrogen, halogen, straight, branched or cyclic alkyl of 1 to 6 carbons, carboxylic acid, carboxyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, N-alkylamino methyl with the alkyl group being straight, branched or cyclic of 1 to 6 carbons, sulfonic acid, sulfonyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, sulfonamide, amine (NH2), mono, di or trialkyl amine with the alkyl being straight, branched or cyclic of 1 to 6 carbons, nitrile, carboxamide, N-alkyl carboxamide of 1 to 6 carbons in the straight, branched or cyclic alkyl group, perfluoroalkyl of 1 to 3 carbons, straight, branched or cyclic alkoxy of 1 to 6 carbons;
- R4 is selected from the group consisting of carboxylic acid, carboxyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, N-alkylaminomethyl with the alkyl group being straight, branched or cyclic of 1 to 6 carbons, sulfonic acid, sulfonyl ester with the ester group being straight, branched or cyclic alkyl of 1 to 6 carbons, sulfonamide, nitrile, carboxamide, N-alkyl carboxamide of 1 to 6 carbons in the straight, branched or cyclic alkyl group, CH2NH2 or CH2OH;
- Ar is unsubstituted phenyl or fluorophenyl.
Dependencies are inferred from the claim text.