Wayne C. Schairer

Design and synthesis of novel conformationally restricted HIV protease inhibitors

A set of HIV protease inhibitors represented by compound 2 has previously been described. Structural and conformational analysis of this compound suggested that conformational restriction of the P1/P2 portion of the molecule could lead to a novel set of potent protease inhibitors. Thus, probe compounds 3-7 were designed, synthesized, and found to be potent inhibitors of HIV protease.

Achiral internucleoside linkages: CH2-CH2-NH and nH-CH2-CH2 linkages

The synthesis of CH2-CH2-NH and NH-CH2-CH2 internucleoside linkages are described. Antisense oligonucleosides containing these dimer modifications hybridized to the sense sequence. Furthermore incorporation of these backbone modifications enhanced the nuclease resistance of the antisense strand.

Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency.

Achiral internucleoside linkages 3: CH2NHCH2 linkage

Abstract A stereoselective method for the synthesis of 3′-α-or 3′-β-carbon substituted pyrimidine nucleosides was developed. The synthesis of the CH 2 NHCH 2 linkage is described. The linkage offers enhanced resistance to 3′-exonuclease.