A comparative SAR and computer modeling study of benzisothiazolone, mechanism-based inhibitors with porcine pancreatic and human leukocyte elastase
✍ Scribed by Dennis J. Hlasta; John J. Court; Ranjit C. Desai; Timothy G. Talomie; Jian Shen; Richard P. Dunlap; Catherine A. Franke; Albert J. Mura
- Publisher
- Elsevier Science
- Year
- 1996
- Tongue
- English
- Weight
- 332 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0960-894X
No coin nor oath required. For personal study only.
✦ Synopsis
Distinct differences in the SAR for HLE and PPE inhibition in this class of compounds were observed. For example, larger lipophilic substituents at the benzisothiazolone 4-position afforded inhibitors that were potent against HLE, but inactive against PPE. These findings are consistent with computer models of inhibitor-enzyme complexes built using the X-ray structure coordinates of HLE and PPE. These models show that substituents at the benzisothiazolone 4-position fit into the S 1 specificity pocket of the enzyme and that other differences in the SAR can be explained based on the structural differences of riLE and PPE.