Noncovalent inhibitors of human leukocyte elastase based on the 4-imidazolidinone scaffold.
A central problem associated with the design of enzyme inhibitors in general, and serine protease inhibitors in particular, is the identification of templates capable of binding to the active site of an enzyme in a predictable and substrate-like fashion, orienting appended recognition elements in a correct spatial relationship so that favorable binding interactions with multiple sites are achieved. Described herein for the first time is the design of noncovalent inhibitors of human leukocyte elastase that employs a functionalized 4-imidazolidinone scaffold.
Wei
Liuqing
L
Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
Gan
Xiangdong
X
Zhong
Jiaying
J
Alliston
Kevin R
KR
Groutas
William C
WC
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy
D004791:Enzyme Inhibitors; D007093:Imidazoles; D019272:Leukocyte Elastase