Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: New lead-agents with analgesic and antipyretic properties

被引：90
作者：
Bezerra-Netto, Heleno J. C.
Lacerda, Daniel I.
Miranda, Ana Luisa P.
Alves, Helio M.
Barreiro, Eliezer J.
Fraga, Carlos A. M.
机构：
[1] Univ Fed Rio de Janeiro, Fac Farm, LASSBio, BR-21944971 Rio De Janeiro, Brazil
[2] Univ Fed Rio de Janeiro, Fac Farm, Programa Mestrado Ciencias Farmaceut, BR-21944971 Rio De Janeiro, Brazil
[3] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Programa Pos Grad Farmacol & Terapeut Expt, Dept Farmacol Basica & Clin, Rio De Janeiro, Brazil
[4] Univ Fed Rio de Janeiro, Fac Farm, Dept Prod Nat & Alimentos, Rio De Janeiro, Brazil
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 23期
关键词：
N-acylhydrazone; safrole; analgesic activity; antipyretic activity; 1,3-benzodioxote derivatives; privileged structure;
D O I：
10.1016/j.bmc.2006.07.046
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In this work, we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5-yloxy)-acetylhydrazone derivatives (3), designed exploring molecular hybridization and isosteric replacement approaches between nimesulide (1) and carbanalogue NAH series (2) developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (4) as starting material. The evaluation of the antinociceptive properties of this series led us to discover a new potent prototype of analgesic and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which showed to be more potent than dipyrone used as standard. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：7924 / 7935
页数：12
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