A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids

被引：69

作者：

Kia, Yalda ^{[1
]}

Osman, Hasnah ^{[1
]}

Kumar, Raju Suresh ^{[2
]}

Murugaiyah, Vikneswaran ^{[3
]}

Basiri, Alireza ^{[3
]}

Perumal, Subbu ^{[4
]}

Razak, Ibrahim Abdul ^{[5
]}

机构：

[1] Univ Sains Malaysia, Sch Chem Sci, Usm 11800, Penang, Malaysia

[2] King Saud Univ, Coll Sci, Dept Chem, Riyadh, Saudi Arabia

[3] Univ Sains Malaysia, Sch Pharmaceut Sci, Usm 11800, Penang, Malaysia

[4] Madurai Kamaraj Univ, Sch Chem, Dept Organ Chem, Madurai 625021, Tamil Nadu, India

[5] Univ Sains Malaysia, Sch Phys, Usm 11800, Penang, Malaysia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 10期

关键词：

AChE; BChE; 1,3-Dipolar cycloaddition; Selectivity and spiropyrrolizines; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE INHIBITORS; SITE GORGE; BUTYRYLCHOLINESTERASE; DERIVATIVES; SUBSTRATE; BINDING; BRAIN; PHASE;

D O I：

10.1016/j.bmcl.2013.03.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and L-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13 mu M, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2979 / 2983

页数：5