title: Discovery of a new class of potent prolylcarboxypeptidase inhibitors derived from alanine.
abstract: Efforts to modify the central proline portion of lead compound 4 lead to the discovery of novel prolylcarboxypeptidase (PrCP) inhibitors. Especially, replacement with alanine afforded compound 19 displaying more potent human and mouse PrCP inhibitory activity than 4 and an overall comparable profile.
authors.affiliation: Department of Discovery Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. zhicai_wu@merck.com
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Wu
authors.forename: Cangming
authors.initials: C
authors.lastname: Yang
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xiong
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Matthew
authors.initials: M
authors.lastname: Lombardo
authors.forename: Andreas
authors.initials: A
authors.lastname: Verras
authors.forename: Renee M
authors.initials: RM
authors.lastname: Chabin
authors.forename: Suoyu
authors.initials: S
authors.lastname: Xu
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Mike E
authors.initials: ME
authors.lastname: Lassman
authors.forename: Urmi R
authors.initials: UR
authors.lastname: Bhatt
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Garcia-Calvo
authors.forename: Wayne
authors.initials: W
authors.lastname: Geissler
authors.forename: Zhu
authors.initials: Z
authors.lastname: Shen
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.forename: Ranabir
authors.initials: R
authors.lastname: Sinharoy
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
authors.forename: Shirly
authors.initials: S
authors.lastname: Pinto
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Shen
authors.forename: Steven L
authors.initials: SL
authors.lastname: Colletti
mesh_terms: D000409:Alanine / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase; D000409:Alanine