Michael A. Patane

Selective α-1A adrenergic receptor antagonists. effects of pharmacophore regio- and stereochemistry on potency and selectivity

The anti-anxiety agent ipsapirone has been shown to have modest affinity for alpha-1 receptors. We disclose the discovery of potent alpha-1a receptor subtype selective antagonists based on the ipsapirone structure which possess selectivity versus the 5-HT receptors tested. These antagonists were obtained by tethering a saccharin ring to 4-phenyl-3-carboxyethyl piperidines. The design principles which led to this structural motif are discussed. The synthesis of key analogs, their SAR, as well as results of selected in vitro and in vivo studies are described.

Expedient synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones

Abstract A new procedure for the synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones is described. Two plausible mechanisms for the key chemical transformation are advanced.

COMPLESTATIN TO CHLOROPEPTIN I VIA A QUANTITATIVE ACID CATALYZED REARRANGEMENT. ABSOLUTE STEREOCHEMICAL DETERMINATION OF COMPLESTATIN

Abstract Complestatin and isomeric chloropeptin I are bicyclo hexapeptides isolated from a Streptomyces sp. Both of these compounds are inhibitors of gp120-CD4 HIV fusion activity. In this paper, we describe an efficient acid catalyzed conversion of complestatin to chloropeptin I, provide a plausible mechanism for this transformation, and unambiguously assign the stereochemistry of complestatin.

Phenylacetamides as selective α-1A adrenergic receptor antagonists

A novel class of potent and selective α-1a receptor antagonists has been identified. The structures of these antagonists were derived from truncating the 4-aryl dihydropyridine subunit present in known α-1a antagonists. The design principles which led to the discovery of substituted phenylacetamides, the synthesis and SAR of key analogues, and the results of select in vitro and in vivo studies are described.

Cyclic imides as potent and selective α-1A adrenergic receptor antagonists

We disclose a new compound class of potent and selective α-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are presented.