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: Synthesis and structure-activity relationship of a novel sulfone series of TNF-alpha converting enzyme inhibitors.
    Author: Xue CB, Chen XT, He X, Roderick J, Corbett RL, Ghavimi B, Liu RQ, Covington MB, Qian M, Ribadeneira MD, Vaddi K, Trzaskos J, Newton RC, Duan JJ, Decicco CP.
    Journal: Bioorg Med Chem Lett; 2004 Sep 06; 14(17):4453-9. PubMed ID: 15357971.
    Abstract:
    Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1-methyl-6-[[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl]5-piperidinecarboxamide) with a sulfonyl group led to a new series of alpha,beta-cyclic and beta,beta-cyclic gamma-sulfonyl hydroxamic acids, which were potent TNF-alpha converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy-(4S,5S)-1-methyl-5-[[4-(2-methyl-4-quinolinylmethoxy)phenyl]sulfonylmethyl]-4-pyrrolidinecarboxamide) exhibited IC50 values of < 1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP-1, -2, -9 and -13 and was orally bioavailable with an F value of 46% in mice.
    [Abstract] [Full Text] [Related] [New Search]