Bioorganic and Medicinal Chemistry Letters p. 5071 - 5075 (2017)
Update date:2022-09-26
Topics:
AlNeyadi, Shaikha S.
Adem, Abdu
Amer, Naheed
Salem, Alaa A.
Abdou, Ibrahim M.
The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small-molecule GLP-1 receptor agonists. In this study, two series of new pyrimidine derivatives were designed and synthesized using an efficient route, and were evaluated in terms of GLP-1 receptor agonist activity. In the first series, novel pyrimidines substituted at positions 2 and 4 with groups varying in size and electronic properties were synthesized in a good yield (78–90%). In the second series, the designed pyrimidine templates included both urea and Schiff base linkers, and these compounds were successfully produced with yields of 77–84%. In vitro experiments with cultured cells showed that compounds 3a and 10a (10?15–10?9 M) significantly increased insulin secretion compared to that of the control cells in both the absence and presence of 2.8 mM glucose; compound 8b only demonstrated significance in the absence of glucose. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1 receptor agonists that can be administered orally.
View MoreZhengzhou Xinlian Chemical Tech Co. ,Ltd
Contact:0371-65771781 021-52042910
Address:H Part, Building I, No. 700 Gonglu Road, Pudong New Area, Shanghai
JIN TAN CHENG'EN CHEMICAL CO.,LTD.
Contact:86-519-82116250
Address:NO.102,village Dongfang,conomic development zone
website:http://www.debyesci.com
Contact:+85221376140
Address:Rm. 19C, Lockhart Ctr., 301-307 Lockhart Rd., Wan Chai
Weifang Yuexiang Chemical Co.,Ltd
Contact:86-536-8734188
Address:Economic development zone Weifang city ,Shandong province ,China
Tianjin Emulsion Science&Technology Development Co.,Ltd
Contact:13901380442
Address:Vake Garden New Town New Yi Bai Road Beichen District Tianjin,China
Doi:10.1016/j.tet.2015.05.001
(2016)Doi:10.1002/jlcr.1698
(2010)Doi:10.1039/b926498a
(2010)Doi:10.1134/S1070428009020284
(2010)Doi:10.1016/j.tetasy.2010.05.027
(2010)Doi:10.1016/j.jorganchem.2010.04.031
(2010)