Synthesis of a Stereochemically Diverse Library of Medium-Sized Lactams and Sultams via SNAr Cycloetherification

被引：33

作者：

Gerard, Baudouin ^{[1
]}

Duvall, Jeremy R. ^{[1
]}

Lowe, Jason T. ^{[1
]}

Murillo, Tiffanie ^{[1
]}

Wei, Jingqiang ^{[1
]}

Akella, Lakshmi B. ^{[1
]}

Marcaurelle, Lisa A. ^{[1
]}

机构：

[1] Harvard & MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA

来源：

ACS COMBINATORIAL SCIENCE | 2011年 / 13卷 / 04期

关键词：

library design; diversity-oriented synthesis; physicochemical properties; diversity-ranking; maximum dissimilarity; sparse matrix; COMBINATORIAL LIBRARY; DRUG DISCOVERY; DOS APPROACH; STRATEGY; DESIGN; METHODOLOGY; SCAFFOLDS; SELECTION; SPACE;

D O I：

10.1021/co2000218

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the Sinksil of SterreocherniCally. diverse 8-membered lactam and sultam Scaffolds: via SNAr cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The.production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).

引用

页码：365 / 374

页数：10

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