Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-X and BCL-2.

The BCL-2 family of proteins (including the prosurvival proteins BCL-2, BCL-X, and MCL-1) is an important target for the development of novel anticancer therapeutics. Despite the challenges of targeting protein-protein interaction (PPI) interfaces with small molecules, a number of inhibitors (called BH3 mimetics) have entered the clinic and the BCL-2 inhibitor, ABT-199/venetoclax, is already proving transformative. For BCL-X, new validated chemical series are desirable.

De-novo designed library of benzoylureas as inhibitors of BCL-XL: synthesis, structural and biochemical characterization.

The prosurvival BCL-2 proteins are attractive yet challenging targets for medicinal chemists. Their involvement in the initiation and progression of many, if not all, tumors makes them prime targets for developing new anticancer therapies. We present our approach based on de novo structure-based drug design.

Remarkable in vitro bactericidal activity of bismuth(III) sulfonates against Helicobacter pylori.

Four new tris-substituted bismuth(III) sulfonates of general formula [Bi(O(3)SR)(3)] (R = phenyl 1, p-tolyl 2, 2,4,6-mesityl 3 and S-(+)-10-camphoryl 4) have been synthesised and characterised. Their synthesis by solvent-free (SF) and solvent-mediated (SM) methods has been explored and their activity against Helicobacter pylori has been investigated. The compounds 1-4 display a remarkable in vitro activity against three laboratory strains of H.

Backbone assignments of the 34 kDa ketopantoate reductase from E. coli.

Ketopantoate reductase is an essential enzyme for pantothenate (vitamin B5) synthesis and a potential antibiotic target. Here we report the 15N and 1HN, 13C', 13C(alpha) and 13C(beta) chemical shift assignments of the 34 kDa ketopantoate reductase in its apo state.

8-Chloro-5-(4-phenethylpiperazin-1--yl)pyrido[2,3-b][1,5]benzoxazepine.

As part of an anti-psychotic drug discovery program, we report the crystal structure of the title compound, C(24)H(23)ClN(4)O. The mol-ecule has a tricyclic framework with a characteristic buckled V-shaped pyridobenzoxazepine unit, with the central seven-membered heterocycle in a boat configuration. The piperazine ring displays a chair conformation with the 2-phenyl-ethyl substituent assuming an equatorial orientation.