Craig K. Esser

Substituted 2-aminopyridines as inhibitors of nitric oxide synthase

A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM.

Inhibition of matrix metalloproteinases by N-carboxyalkyl dipeptides: Enhanced potency and selectivity with substituted P1′ homophenylalanines

Abstract A series of N-carboxyalkyl dipeptides were synthesized to evaluate their inhibitory activities against human stromelysin-1(MMP-3), collagenase(MMP-1), and gelatinase-A(MMP-2). Structures with a homophenylalanine residue at P 1′ substituted at the para position with small alkyl groups are potent inhibitors of (MMP-3) and (MMP-2) (K i′ s 2–40 nM), but weak inhibitors of (MMP-1).

Solid-phase synthesis of a N-carboxyalkyl tripeptide combinatorial library

Abstract A combinatorial library of N-carboxyalkyl tripeptides was prepared to generate new leads against metalloproteinases. Using the base labile TentaGel S HMB resin, an Fmoc strategy was employed to yield 100 mixtures of 200 compounds each of the general structure 5. A synthetic protocol combining both mix and split and indexed combinatorial strategies was used, and selected inhibition data against MMP-3 is reported.

The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties

Amino-anthranilic acid derivatives have been identified as a new class of low serum shifted, high affinity full agonists of the human orphan G-protein-coupled receptor GPR109a with improved ADME properties.

GPR109a agonists. Part 1: 5-Alkyl and 5-aryl-pyrazole–tetrazoles as agonists of the human orphan G-protein coupled receptor GPR109a

5-Alkyl and aryl-pyrazole-tetrazoles have been identified as a new class of selective, small-molecule, agonists of the human G-protein-coupled receptor GPR109a, a high affinity receptor for the HDL-raising drug nicotinic acid.

Synthesis of di- and trisubstituted guanidines on multivalent soluble supports

Abstract A library of 48 di- and trisubstituted guanidines was synthesized on a soluble, tetravalent support. Support-bound intermediates and cleaved products were isolated in parallel by size exclusion chromatography using a semiautomated system. Products were generally obtained in good yield and purity.

GPR109a agonists. Part 2: Pyrazole-acids as agonists of the human orphan G-protein coupled receptor GPR109a

5-Alkyl and aryl-pyrazole-acids have been identified as a new class of selective, small-molecule, agonists of the human orphan G-protein-coupled receptor GPR109a, a high affinity receptor for the HDL-raising drug nicotinic acid.