Scott A. Biller

A solid phase synthesis of miconazole analogs via an iodoetherification reaction

Abstract A procedure for the preparation of various analogs of miconazole on solid support is described. A novel iodoetherification transformation is utilized as the key synthetic step. This approach has been applied to the combinatorial synthesis of 45 analogs.

Microsomal triglyceride transfer protein inhibitors: discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents

A series of newly synthesized phosphonate esters were evaluated for their effects on microsomal triglyceride transfer protein activity (MTP). The most potent compounds were evaluated for their ability to inhibit lipoprotein secretion in HepG2 cells and to affect VLDL secretion in rats. These inhibitors were also found to lower serum cholesterol levels in a hamster model upon oral dosing.

Aromatic isosteres as conformational probes for an isoprenyl subunit: application to inhibitors of squalene synthase

Abstract A series of aromatic isosteres of the farnesyl chain of potent squalene synthase inhibitor 1 were prepared and evaluated. The results are consistent with the local conformation indicated in structure 2 .

Tetrazole based amides as growth hormone secretagogues

A novel series of N1 substituted tetrazole amides were prepared and showed to be potent growth hormone (GH) secretagogues. Among them, hydroxyl containing analog 31 displayed excellent in vivo activity by increasing plasma GH 10-fold in an anesthetized IV rat model.

Optimization of 1H-tetrazole-1-alkanenitriles as potent orally bioavailable growth hormone secretagogues.

1H-tetrazole-1-alkanenitrile SR-9g exhibits a >10-fold in vivo potency enhancement over the lead nitrile 1 and has acceptable oral bioavailability in rats and dogs. An enantiospecific synthesis of 1H-tetrazole-1-alkanenitrile nitriles 9 has been developed.