4'-Methyl-4,5'-bithiazole-based correctors of defective delta F508-CFTR cellular processing.

The synthesis and Delta F508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human Delta F508-CFTR.

Aminodeoxychorismate synthase inhibitors from one-bead one-compound combinatorial libraries: "staged" inhibitor design.

4-Amino-4-deoxychorismate synthase (ADCS) catalyzes the first step in the conversion of chorismate into p-aminobenzoate, which is incorporated into folic acid. We aim to discover compounds that inhibit ADCS and serve as leads for a new class of antimicrobial compounds. This report presents (1) synthesis of a mass-tag encoded library based on a "staged" design, (2) massively parallel fluorescence-based on-bead screening, (3) rapid structural identification of hits, and (4) full kinetic analysis of ADCS.

Stannous chloride in alcohol: a one-pot conversion of 2-nitro-N-arylbenzamides to 2,3-dihydro-1H-quinazoline-4-ones.

A novel one-step synthesis of 2,3-dihydro-1H-quinazolin-4-ones from 2-nitrobenzamides is reported. These reactions are mediated by stannous chloride in 0.02 M methanolic or ethanolic HCl solution and proceed in good yields.

Tweezer-type neutral carrier-based calcium-selective membrane electrode with drastically reduced anionic interference.

A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N-methylcarbamoyl-methoxyacetamidoacetoxy)-5beta-cholan-24-amide (denoted as BACA), was synthesized, and its potentiometric performance has been evaluated in comparison with that of the best known calcium-selective neutral carriers, ETH 129 and ETH 1001. The 1H NMR spectra of BACA titrated with Ca(SCN)2 suggest that BACA forms a 1:1 complex, tweezing a calcium ion between the two parallel diamide groups substituted on a rigid bile acid frame. The calcium-selective membrane based on BACA was less selective to calcium (log K(Ca2+ j)POT = -4.