Anticancer Agents Based on a New Class of Transition- State Analog Inhibitors for Serine and Cysteine Proteases.
Abstract
In this report we describe our efforts to develop a new class of competitive inhibitors for serine and cysteine proteases. These compounds are potential anticancer agents that would act by inhibiting metastasis and angiogenesis. The first part of this report describes solution and solid phase methods for the synthesis of inhibitors of the cysteine protease cathepsin B. These inhibitors are based on a cyclohexanone pharmacophore and are designed to interact with both the S and S' subsites of the enzyme active site. In the second part we demonstrate that the 4-heterocyclohexanone pharmacophore can be used to synthesize effective inhibitors of serine proteases. We have constructed an inhibitor of the serine protease plasmin, and shown that it has good activity and significant specificity for plasmin over other proteases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA355419
Entities
People
- Chrchristopher T. Seto
Organizations
- Brown University