These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A new class of prolylcarboxypeptidase inhibitors, part 2: the aminocyclopentanes.
    Author: Graham TH, Liu W, Verras A, Reibarkh M, Bleasby K, Bhatt UR, Chen Q, Garcia-Calvo M, Geissler WM, Gorski JN, He H, Lassman ME, Lisnock J, Li X, Shen Z, Tong X, Tung EC, Wiltsie J, Xie D, Xu S, Xiao J, Hale JJ, Pinto S, Shen DM.
    Journal: Bioorg Med Chem Lett; 2012 Apr 15; 22(8):2818-22. PubMed ID: 22444685.
    Abstract:
    A series of potent inhibitors of prolylcarboxypeptidase (PrCP) was developed by modifying a lead structure that was discovered by high-throughput screening. The tert-butyl pyrrolidine was replaced by an aminocyclopentane to reduce the metabolic liabilities of the original lead. The compounds demonstrated sub-nanomolar in vitro IC(50) values, minimal activity shifts in pure plasma and improved pharmacokinetics. Complete ex vivo plasma target engagement was achieved with low brain exposure at the 20 h time point following p.o. dosing in a mouse. The results indicate that the aminocyclopentanes are useful tools for studying the therapeutic potential of peripheral (non-CNS) PrCP inhibition.
    [Abstract] [Full Text] [Related] [New Search]