Chen_2015_J.Med.Chem_58_8529

Reference

Title : Discovery of a Novel Series of Imidazo[1,2-a]pyrimidine Derivatives as Potent and Orally Bioavailable Lipoprotein-Associated Phospholipase A2 Inhibitors - Chen_2015_J.Med.Chem_58_8529
Author(s) : Chen X , Xu W , Wang K , Mo M , Zhang W , Du L , Yuan X , Xu Y , Wang Y , Shen J
Ref : Journal of Medicinal Chemistry , 58 :8529 , 2015
Abstract : Inhibition of lipoprotein-associated phospholipase A2 (Lp-PLA2) has been suggested to be a promising therapeutic strategy for several inflammation-associated diseases, including atherosclerosis, Alzheimer's disease, and diabetic macular edema. Herein, we report the discovery of a novel series of Lp-PLA2 inhibitors constructed on an imidazo[1,2-a]pyrimidine scaffold through a conformational restriction strategy. Structure-activity relationship (SAR) analysis resulted in the identification of several compounds with high potency in vitro and good metabolic stability in liver S9 fractions. Compounds 7c and 14b selected for further exploration in vivo demonstrated excellent pharmacokinetic profiles and exhibited significant inhibitory efficacy in SD rats upon oral dosing.
ESTHER : Chen_2015_J.Med.Chem_58_8529
PubMedSearch : Chen_2015_J.Med.Chem_58_8529
PubMedID: 26479945
Gene_locus related to this paper: human-PLA2G7

Related information

Gene_locus related to this paper: human-PLA2G7

Citations formats

Chen X, Xu W, Wang K, Mo M, Zhang W, Du L, Yuan X, Xu Y, Wang Y, Shen J (2015)
Discovery of a Novel Series of Imidazo[1,2-a]pyrimidine Derivatives as Potent and Orally Bioavailable Lipoprotein-Associated Phospholipase A2 Inhibitors
Journal of Medicinal Chemistry 58 :8529

Chen X, Xu W, Wang K, Mo M, Zhang W, Du L, Yuan X, Xu Y, Wang Y, Shen J (2015)
Journal of Medicinal Chemistry 58 :8529