Effect of functional group polarity on the antimalarial activity of spiro and dispiro-1,2,4-trioxolanes

被引：57

作者：

Dong, Yuxiang

Tang, Yuanqing

Chollet, Jacques

Matile, Hugues

Wittlin, Sergio

Charman, Susan A.

Charman, William N.

Tomas, Josefina Santo

Scheurer, Christian

Snyder, Christopher

Scorneaux, Bernard

Bajpai, Saroi

Alexander, Scott A.

Wang, Xiaofang

Padmanilayam, Manlyan

Cheruku, Srinivasa R.

Brun, Reto

Vennerstrom, Jonathan L.

机构：

[1] Univ Nebraska, Med Ctr, Coll Pharm, Omaha, NE 68182 USA

[2] Swiss Trop Inst, CH-4002 Basel, Switzerland

[3] F Hoffmann La Roche Ltd, CH-4070 Basel, Switzerland

[4] Monash Univ, Victorian Coll Pharm, Ctr Drug Candidate Optimisat, Parkville, Vic 3052, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 18期

关键词：

1,2,4-trioxolane; secondary ozonide; antimalarial; artemisinin;

D O I：

10.1016/j.bmc.2006.05.041

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：

Based on the structures of several lipophilic trioxolane antimalarial prototypes, we set out to determine which functional groups were associated with good antimalarial profiles and identify more polar (lower LogP/LogD) lead compounds with good physicochemical properties. More lipophilic trioxolanes tended to have better oral activities than their more polar counterparts. Trioxolanes with a wide range of neutral and basic, but not acidic, functional groups had good antimalarial profiles. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：6368 / 6382

页数：15

共 30 条

[21]

Tang YQ, 2004, SYNTHESIS-STUTTGART, P2540

[22] Synthesis of tetrasubstituted ozonides by the griesbaum coozonolysis reaction: Diastereoselectivity and functional group transformations by post-ozonolysis reactions [J].