New 6-amino-pyrido[2,3-d]pyrimidine-2,4-diones as novel agents to treat type 2 diabetes: A simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study

被引：81

作者：

Adib, Mehdi ^{[1
]}

Peytam, Fariba ^{[1
]}

Rahmanian-Jazi, Mahmoud ^{[1
]}

Mahernia, Shabnam ^{[2
,3
]}

Bijanzadeh, Hamid Reza ^{[4
]}

Jahani, Mehdi ^{[1
]}

Mohammadi-Khanaposhtani, Maryam ^{[5
]}

Imanparast, Somaye ^{[6
]}

Faramarzi, Mohammad Ali ^{[6
]}

Mahdavi, Mohammad ^{[7
]}

Larijani, Bagher ^{[7
]}

机构：

[1] Univ Tehran, Sch Chem, Coll Sci, POB 14155-6455, Tehran, Iran

[2] Univ Tehran, Drug Design & Dev Res Ctr, Fac Pharm, Dept Med Chem, Tehran, Iran

[3] Univ Tehran, Pharmaceut Sci Res Ctr, Inst Pharmaceut Sci, Tehran, Iran

[4] Tarbiat Modares Univ, Fac Nat Resources & Marine Sci, Dept Environm Sci, Nur, Mazandaran, Iran

[5] Babol Univ Med Sci, Hlth Res Inst, Cellular & Mol Biol Res Ctr, Babol Sar, Iran

[6] Univ Tehran Med Sci, Fac Pharm & Biotechnol Res Ctr, Dept Pharmaceut Biotechnol, Tehran, Iran

[7] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 155卷

关键词：

ONE-POT; DERIVATIVES;

D O I：

10.1016/j.ejmech.2018.05.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 6-amino-pyrido[2,3-d]pyrimidine-2,4-dione derivatives 3a-3s were prepared via a facile and efficient reaction from alpha-azidochalcones and 6-amiouracils. The reactions were performed under mild conditions to produce the corresponding compounds in good to excellent yields. Obtained derivatives 3a-3s were evaluated for alpha-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast a-glucosidase inhibition with IC50 values ranging from 78.0 +/- 2.0 to 252.4 +/- 1.0 mu M. For example, the most active compound 3o was around 10-fold more potent than acarbose, a standard drug (IC50 = 750.0 +/- 1.5 mu M). Kinetic study of compound 3o revealed that it inhibited alpha-glucosidase in a competitive mode. Molecular modeling studies of the most active compounds 3o, 3i, 3e and 3m were also performed. (C) 2018 Elsevier Masson SAS. All rights reserved.

引用

页码：353 / 363

页数：11

共 25 条

[1] A new synthetic strategy towards 2,4,5-trisubstituted 1&ITH&IT-imidazoles and highly substituted pyrrolo[1,2-&ITc&IT]imidazoles by use of α-azidochalcones &ITvia&IT Michael addition-cyclization followed by Wittig reaction [J].