Carboxylic acid (bio)isosteres in drug design.
Carboxylic acid (bio)isosteres in drug design.
复制标题
DOI：
10.1002/cmdc.201200585
复制
发表时间：
2013-03
期刊：
影响因子：
3.4
通讯作者：
Smith, Amos B., III
中科院分区：
文献类型：
--
作者：
Ballatore, Carlo;Huryn, Donna M.;Smith, Amos B., III
羧酸官能团可以是药效团的重要组成部分，然而，这种官能团的存在也可能导致显著的缺点，包括代谢不稳定、毒性以及有限的被动扩散通过生物膜。为了避免其中的一些缺点，同时保留所需的属性的羧酸部分，药物化学家经常研究使用羧酸(生物)等位体。同样类型的战略也可以有效地用于各种其他目的，例如，增加生物活性化合物的选择性或创造新的知识产权。已经报道了几个羧酸等位体，然而，任何等位体取代的结果都不容易预测，因为这一策略通常被发现依赖于特定的背景(即，药物和药物靶标的特征性质)。因此，通常需要对一组同位素体进行筛选。在这种背景下，发现和开发能够补充现有同位素调色板的新型羧酸替代品仍然是一个重要的研究领域。这篇小综述的目的是提供最常用的羧酸(BIO)同工酶的概述，并提供具有代表性的例子，说明每种同工酶在药物设计中的用途和用途。
The carboxylic acid functional group can be an important constituent of a pharmacophore, however, the presence of this moiety can also be responsible for significant drawbacks, including metabolic instability, toxicity, as well as limited passive diffusion across biological membranes. To avoid some of these shortcomings while retaining the desired attributes of the carboxylic acid moiety, medicinal chemists often investigate the use of carboxylic acid (bio)isosteres. The same type of strategy can also be effective for a variety other purposes, for example, to increase the selectivity of a biologically active compound or to create new intellectual property. Several carboxylic acid isosteres have been reported, however, the outcome of any isosteric replacement cannot be readily predicted as this strategy is generally found to be dependent upon the particular context (i.e., the characteristic properties of the drug and the drug–target). As a result, screening of a panel of isosteres is typically required. In this context, the discovery and development of novel carboxylic acid surrogates that could complement the existing palette of isosteres remains an important area of research. The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio)isosteres and to present representative examples demonstrating the use and utility of each isostere in drug design.
登录
查看更多内容
影响因子：
4.1
作者：
Alvarez-Sanchez, Ruben;Montavon, Francois;Paehler, Axel
通讯作者：
Paehler, Axel
影响因子：
7.3
作者：
Frolund, B;Jensen, LS;Liljefors, T
通讯作者：
Liljefors, T
影响因子：
3.6
作者：
Bunch, L;Krogsgaard-Larsen, P;Madsen, U
通讯作者：
Madsen, U
影响因子：
3.5
作者：
Costantino, G;Maltoni, K;Pellicciari, R
通讯作者：
Pellicciari, R
影响因子：
15
作者：
Bell, PH;Roblin, RO Jr
通讯作者：
Roblin, RO Jr