Solid-State Perturbation for Solubility Improvement: A Proof of Concept

被引：12

作者：

Briggner, Lars-Erik ^{[2
]}

Hendrickx, Ramon ^{[3
]}

Kloo, Lars ^{[4
]}

Rosdahl, Jan ^{[4
]}

Svensson, Per H. ^{[1
,4
]}

机构：

[1] AstraZeneca R&D Sodertalje, AstraZeneca Pharm Dev, S-15185 Sodertalje, Sweden

[2] AstraZeneca Pharm Dev, S-22187 Lund, Sweden

[3] AstraZeneca DMPK, S-22187 Lund, Sweden

[4] Royal Inst Technol, Sch Chem Sci & Engn, S-10044 Stockholm, Sweden

来源：

CHEMMEDCHEM | 2011年 / 6卷 / 01期

关键词：

ab initio calculations; crystal packing; drug design; solubility; X-ray diffraction; PREDICTION;

D O I：

10.1002/cmdc.201000405

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Simple and rational: The intrinsic solubility of a compound can be systematically improved by perturbing key interactions in its crystal structure. By carefully choosing the perturbation, the end result will be a molecule similar to the original one, but with significantly higher solubility. This methodology is demonstrated on a subset of benzodiazepines, resulting in significant improvement of their solubility. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：60 / 62

页数：3

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