Potential protease inhibitors based on a functionalized cyclic sulfamide scaffold
Date
2004-07-01Author
Zhong, Jiaying
Gan, Xiangdong
Alliston, Kevin R.
Lai, Zhong
Yu, Hongyi
Groutas, Christopher S.
Wong, Tzutshin
Groutas, William C.
Metadata
Show full item recordCitation
Journal of combinatorial chemistry. 2004 Jul-Aug; 6(4): 556-63.
Abstract
Exploratory studies related to the design and synthesis of functionalized cyclic sulfamides (I) as potential inhibitors of proteolytic enzymes were carried out. The structural motif and three diversity sites embodied in the scaffold render it amenable to combinatorial parallel synthesis and the facile generation of lead discovery prospecting libraries. The scaffold was readily assembled starting with (DL) serine methyl ester, and a series of compounds was generated and screened against human leukocyte elastase. Modification of the P(1) recognition element, believed to be accommodated at the primary specificity site (S(1) subsite) of the enzyme, yielded compounds that inhibited the enzyme by an apparent hyperbolic partial mixed-type inhibition.
Description
Click on the DOI link below to access the article (may not be free).