Synthesis and evaluation of novel 2-pyridone derivatives as inhibitors of phosphodiesterase3 (PDE3): A target for heart failure and platelet aggregation

被引：54

作者：

Ravinder, Mettu ^{[2
]}

Mahendar, Budde ^{[2
]}

Mattapally, Saidulu ^{[3
]}

Hamsini, Kommi Venkata ^{[2
,3
]}

Reddy, Thatikonda Narendar ^{[2
]}

Rohit, Chilappa ^{[1
]}

Srinivas, Kolupula ^{[1
]}

Banerjee, Sanjay Kumar ^{[3
]}

Rao, Vaidya Jayathirtha ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res, Hyderabad 500037, Andhra Pradesh, India

[2] Indian Inst Chem Technol, Organ Chem Div 2, Hyderabad 500607, Andhra Pradesh, India

[3] Indian Inst Chem Technol, Div Pharmacol, Hyderabad 500607, Andhra Pradesh, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 18期

关键词：

Baylis-Hillman acetates; Enamines; 2-Pyridone derivatives; PDE3; inhibition; Docking studies; Leads; BAYLIS-HILLMAN ADDUCTS; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; SUBSTITUTED; 2-CHLORONICOTINALDEHYDES; BIOLOGICAL EVALUATION; AGENTS; IDENTIFICATION; HYDROGENATION; MODULATION; CILOSTAZOL; MILRINONE;

D O I：

10.1016/j.bmcl.2012.05.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Twenty-six 2-pyridone derivatives (8a-8z), which are structurally analogous to amrinone and milrinone two important cardiotonic drugs, are synthesized and characterized. The synthesis of 2-pyridone derivatives involves addition, followed by cyclization between Baylis-Hillman acetates (7a-7k) and enamino esters or nitriles (3a-3e). Thus synthesized pyridones were subjected to PDE3 inhibitory activity, 14 pyridones were found to be hits out of 26 pyridones synthesized and out of 14 hits, there are 5 pyridones found to be lead compounds having excellent PDE3 inhibitory activity. Further we have carried out computational analysis to understand protein/enzyme and 2-pyridone derivative interactions to identify amino acid residues involved in the vicinity of binding and compared with milrinone drug. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：6010 / 6015

页数：6