Steven R. Schow

The use of HIV-1 protease structure in inhibitor design☆

Abstract The X-ray structure of HIV-1 protease and molecular dynamics studies were used in the design of pseudo-symmetrical enzyme inhibitors 1 and 2 . Short bidirectional syntheses of these compounds are described.

An asymmetric synthesis of differentially protected meso-2,6-diaminopimelic acid

Abstract meso -2,6-Diaminopimelic acid, an important linking component of bacterial cell walls and a biosynthetic precursor of l -lysine has been prepared differentially protected in a stereospecific manner from both l -aspartic and l -glutamic acid. The key step to establish the second chiral center involves the asymmetric reduction of a pyruvate moiety with Alpine-Borane®. S -2-Amino-6-oxopimelic acid, the hydrolyzed open chain form of tetrahydrodipicolinic acid, a biosynthetic precursor of meso -2,6-diaminopimelic acid, was also prepared via deprotection of the key pyruvate intermediate.

Synthesis and biological evaluation of a series of HIV-1 protease inhibitors

Abstract A series of HIV-1 protease inhibitors was prepared and evaluated against the free enzyme for inhibition properties, and for their anti-viral properties in human T lymphoid cells infected with HIVIIIB. Compounds 12, and 19 are the most potent anti-viral agents prepared in this study and are compared to Ro 31-8959, a compound currently in clinical trials for the treatment of AIDS.

Design, structure activity and x-ray crystallographic studies of pseudosymmetrical nonpeptidyl HIV-1 protease inhibitors

Abstract A new class of nonamino acid derived HIV-1 protease inhibitors of structure 1 are described. Structure activity relationships are discussed in the context of a protein crystal complex.

A synthesis or indolizidines related to castanospermine and swainsonine.

Abstract A general synthetic route to indolizidine alkaloids which are structurally similar to castanospermine and swainsonine is described. The described route uses modified pentose sugars and chiral reagents to control the absolute configuration at each asymmetric center.

Structure activity studies on pseudo-symmetrical HIV-1 protease inhibitors

Abstract Lead compound 1, obtained from a previously reported structure-assisted design approach, was optimized to 17 using a traditional medicinal chemistry approach.