title: Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.
abstract: A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.
authors.affiliation: Shanghai Hengrui Pharmaceuticals Co., Ltd, Shanghai, China. tangpc@shhrp.com
authors.forename: Tang Peng
authors.initials: TP
authors.lastname: Cho
authors.forename: Yang Fang
authors.initials: YF
authors.lastname: Long
authors.forename: Lin Zhi
authors.initials: LZ
authors.lastname: Gang
authors.forename: Wang
authors.initials: W
authors.lastname: Yang
authors.forename: Lu He
authors.initials: LH
authors.lastname: Jun
authors.forename: Shen Guang
authors.initials: SG
authors.lastname: Yuan
authors.forename: Fu Jian
authors.initials: FJ
authors.lastname: Hong
authors.forename: Wang
authors.initials: W
authors.lastname: Lin
authors.forename: Guan Dong
authors.initials: GD
authors.lastname: Liang
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lei
authors.forename: Luo Jing
authors.initials: LJ
authors.lastname: Jing
authors.forename: Gong Ai
authors.initials: GA
authors.lastname: Shen
authors.forename: She Gao
authors.initials: SG
authors.lastname: Hong
authors.forename: Wang
authors.initials: W
authors.lastname: Dan
authors.forename: Feng
authors.initials: F
authors.lastname: Ying
authors.forename: Yan Pang
authors.initials: YP
authors.lastname: Ke
authors.forename: Leng
authors.initials: L
authors.lastname: Ying
authors.forename: Feng
authors.initials: F
authors.lastname: Jun
authors.forename: Mong Xian
authors.initials: MX
authors.lastname: Tai
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D009795:Octanes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D001391:Azo Compounds; D001643:Bridged Bicyclo Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009795:Octanes; D018819:Dipeptidyl Peptidase 4