Shahzad Sharooq Rahman

The discovery of a selective, small molecule agonist for the MAS-related gene X1 receptor.

The novel 7-transmembrane receptor MrgX1 is located predominantly in the dorsal root ganglion and has consequently been implicated in the perception of pain. Here we describe the discovery and optimization of a small molecule agonist and initial docking studies of this ligand into the receptor in order to provide a suitable lead and tool compound for the elucidation of the physiological function of the receptor.

A solid-phase synthetic route to substituted 7-azabenzimidazoles suitable for combinatorial library synthesis

Abstract A novel route for the solid-phase synthesis of 1,2,5-substituted 7-azabenzimidazole derivatives has been developed. Primary amines are attached to an aldehyde resin then coupled to 6-chloro-5-nitro-nicotinyl chloride. Subsequent alkylation with amines, reduction of the nitro group and cyclisation with aldehydes gives 1,2,5-substituted 7-azabenzimidazole derivatives.

Inhibitors of human collagenase: dipeptide mimetics with lactam and azalactam moieties at the P2′P3′ position

Abstract A series of thiol-, aminophosphonic acid-, and hydroxamic acid-containing collagenase inhibitors, with lactam and azalactam P 2′ P 3′ substituents has been prepared and evaluated in vitro as inhibitors of human fibroblast collagenase. The most potent inhibitor was the hydroxamic acid 17a (IC50 12 nM). Introduction of a basic amino function into the lactam ring had little effect on potency, but greatly enhanced aqueous solubility.

Synthesis of aminoazalactams as cyclic mimetics of basic alkyl amino acids

Novel medium ring conformationaly constrained amino acid derivatives 2 for incorporation into collagenase inhibitors were prepared, utilising natural amino acids as starting materials, via a reductive intramolecular imine cyclisation.