Synthesis and Stability of Oxetane Analogs of Thalidomide and Lenalidomide

被引：66

作者：

Burkhard, Johannes A. ^{[1
]}

Wuitschik, Georg ^{[2
]}

Plancher, Jean-Marc ^{[2
]}

Rogers-Evans, Mark ^{[2
]}

Carreira, Erick M. ^{[1
]}

机构：

[1] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland

[2] F Hoffmann La Roche & Cie AG, PRED, Discovery Chem, CH-4070 Basel, Switzerland

来源：

ORGANIC LETTERS | 2013年 / 15卷 / 17期

关键词：

TUNICAMYCIN ANTIBIOTICS; DRUG DISCOVERY; DERIVATIVES; METABOLISM;

D O I：

10.1021/ol401705a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Oxetanes are used in drug discovery to enable physicochemical and metabolic property enhancement for the structures to which they are grafted. An imide C=O to oxetane swap on thalidomide and lenalidomide templates provides analogs with similar physicochemical and in vitro properties of the parent drugs, with an important exception: oxetane analog 2 displays a clear differentiation with respect to human plasma stability. The prospect of limiting in vivo stability/metabolism, blocking in vivo racemization, and potentially altering teratogenicity is appealing.

引用

页码：4312 / 4315

页数：4

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