Article

Bicyclic cyanothiazolidines as novel dipeptidyl peptidase 4 inhibitors.

Phenomix Corporation, 5871 Oberlin Drive, Suite 200, San Diego, CA 92121, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.65). 06/2009; 19(15):4437-40. DOI: 10.1016/j.bmcl.2009.05.048
Source: PubMed

ABSTRACT The synthesis and biochemical evaluation of novel cyanothiazolidine inhibitors of dipeptidyl peptidase 4 (DPP4) is described. Their main structural feature is a constrained bicyclic core that prevents the intramolecular formation of inactive cyclic species. The inhibitors show good to moderate biochemical potency against DPP4 and display distinct selectivity profiles towards DPP7, DPP8 and DPP9 depending on their substitution.

0 Bookmarks
 · 
60 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chiral sulfoxides/N-oxides (R)- and (R,R)- are effective chiral promoters in the enantioselective allylation of α-keto ester N-benzoylhydrazone derivatives to generate the corresponding N-benzoylhydrazine derivatives , with enantiomeric excesses as high as 98%. Representative hydrazine derivatives were subsequently treated with SmI2 , and the resulting amino esters with LiOH to obtain quaternary α-substituted α-allyl α-amino acids , whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data. Chirality 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
    Chirality 07/2013; · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Contemporary medicinal chemistry faces diverse challenges from several directions, including the need for both potency and specificity of any therapeutic agent; the increasingly demanding requirements of low toxicity shown across all patients treated; and the need for novelty in intellectual property, given the extensive use of benzenoid and heteroaromatic ring systems in numerous patents. Increasingly, such challenges are being met by a shift to new and/or unusual ring systems (scaffolds) that lie outside the field of (hetero)aromatic systems. This critical review surveys a necessarily limited selection of currently atypical scaffolds, chiefly drawn from the literature of the last three years, that have found application in medicinal chemistry, some being present in agents with therapeutic potential while others are found in agents already in clinical use (163 references).
    Chemical Society Reviews 08/2011; 40(11):5514-33. · 24.89 Impact Factor