Sulfonamide-Based Acyclic and Conformationally Constrained MMP Inhibitors: From Computer-Assisted Design to Nanomolar Compounds

Title: Sulfonamide-Based Acyclic and Conformationally Constrained MMP Inhibitors: From Computer-Assisted Design to Nanomolar Compounds

Volume: 4 Issue: 12

Author(s): Stephen Hanessian and Nicolas Moitessier

Affiliation:

Keywords: computer assisted design, mmp inhibitors, constrained hydroxamic acids, tetrahydrofuran, aziridine, pyrrolidine

Abstract: The present account relates to our studies in the computer assisted design and synthesis of acyclic and cyclic MMP inhibitors. Our early efforts focused on the preparation of cyclopropane and tetrahydrofuran-based mimics of batimastat which were not active. The discovery of subnanomolar sulfonamide-based acyclic inhibitors instigated the design of novel target compounds. Thus, with the help of a fully automated and reliable docking program, we embarked on the design and synthesis of enantiopure inhibitors incorporating cyclic scaffolds. This ultimately led to compounds exhibiting inhibitory activities in the nanomolar range. Interestingly, the qualitative ranking prediction was found to be in good agreement with the observed activities.

Cite this article as:

Hanessian Stephen and Moitessier Nicolas, Sulfonamide-Based Acyclic and Conformationally Constrained MMP Inhibitors: From Computer-Assisted Design to Nanomolar Compounds, Current Topics in Medicinal Chemistry 2004; 4 (12) . https://dx.doi.org/10.2174/1568026043387953