Discovery of conformationally rigid 3-azabicyclo[3.1.0]hexane-derived dipeptidyl peptidase-IV inhibitors.
The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P(2) region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure-activity relationship, and selectivity against related proteases are delineated.
Sattigeri
Jitendra A
JA
Department of Medicinal Chemistry, Ranbaxy Research Laboratories, Gurgaon 122001, India. jitendra.sattigeri@ranbaxy.com
Andappan
Murugaiah M S
MM
Kishore
Kaushal
K
Thangathirupathy
Srinivasan
S
Sundaram
Sinduja
S
Singh
Shuchita
S
Sharma
Suchitra
S
Davis
Joseph A
JA
Chugh
Anita
A
Bansal
Vinay S
VS
D020816:Amino Acid Motifs; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000628:therapy; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015195:Drug Design; D006586:Hexanes / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects*
C532932:3-azabicyclo(3.1.0)hexane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006586:Hexanes; D008024:Ligands; D010880:Piperidines; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4