title: Bicyclic cyanothiazolidines as novel dipeptidyl peptidase 4 inhibitors.
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.
authors.affiliation: Phenomix Corporation, 5871 Oberlin Drive, Suite 200, San Diego, CA 92121, USA. juan.betancort@phenomixcorp.com
authors.forename: Juan M
authors.initials: JM
authors.lastname: Betancort
authors.forename: David T
authors.initials: DT
authors.lastname: Winn
authors.forename: Ruzhang
authors.initials: R
authors.lastname: Liu
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Xu
authors.forename: Junjuan
authors.initials: J
authors.lastname: Liu
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liao
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Carney
authors.forename: Denise
authors.initials: D
authors.lastname: Hanway
authors.forename: James
authors.initials: J
authors.lastname: Schmeits
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Li
authors.forename: Eric
authors.initials: E
authors.lastname: Gordon
authors.forename: David A
authors.initials: DA
authors.lastname: Campbell
mesh_terms: D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003920:Diabetes Mellitus / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011759:Pyrrolidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D053961:Azabicyclo Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D013844:Thiazoles; D053778:Thiazolidines