Abstract

DESIGN AND SYNTHESIS OF 2-SUBSTITUTED-1HBENZIMIDAZOLE- 4-CARBOXAMIDES AS INHIBITORS OF POLY (ADP-RIBOSE) POLYMERASE-1 (PARP-1)

Kalam Bhupathi Reddy, Kiran Kumar Murahari, Sunitha Kanakam, Kombu Subramanaian Rajan, Gangula Mohan Rao, Baru Vijaya Kumar*

ABSTRACT

Novel 2-subtituted-1H-benzimidazole-4-carboxamide poly (ADPribose) polymerase-1 (PARP-1) inhibitors have been synthesized by treating 2-(trichloromethyl)-1H-benzo[d]imidazole-4-carboxamide (4) with various amines in acetonitrile medium using potassium carbonate as base. The compound 4 was synthesised from 2-amino-3- nitrobenzoicacid (1). All the synthesized compounds have been characterized by 1H NMR and Mass spectral data together with elemental analysis. The synthesised compounds (6a-6f) were screened for PARP-1 inhibitory activity. Among these 5a (IC50= 31nM) and 5b ((IC50= 51nM)) were highly active PARP-1 inhibitors.

Keywords: 1H-benzimidazole-4-carboxamide, PARP inhibitors, IC50.