Opportunities for Tapping into Three-Dimensional Chemical Space through a Quaternary Carbon.,Journal of Medicinal Chemistry

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Opportunities for Tapping into Three-Dimensional Chemical Space through a Quaternary Carbon.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-08-17 , DOI: 10.1021/acs.jmedchem.0c00829
Tanaji T Talele ₁

Affiliation

A quaternary carbon bears four other carbon substituents or combination of four non-hydrogen substituents at four vertices of a tetrahedron. The spirocyclic quaternary carbon positioned at the center of a bioactive molecule offers conformational rigidity, which in turn reduces the penalty for conformational entropy. The quaternary carbon is a predominant feature of natural product structures and has been associated with more effective and selective binding to target proteins compared to planar compounds with a high sp² count. The presence of a quaternary carbon stereocenter allows the exploration of novel chemical space to obtain new molecules with enhanced three-dimensionality. These characteristics, coupled to an increasing awareness to develop sp³-rich molecules, boosted utility of quaternary carbon stereocenters in bioactive compounds. It is hoped that this Perspective will inspire the chemist to utilize quaternary carbon stereocenters to enhance potency, selectivity, and other drug-like properties.

中文翻译：

通过季碳进入三维化学空间的机会。

季碳在四面体的四个顶点上带有四个其他碳取代基或四个非氢取代基的组合。位于生物活性分子中心的螺环季碳原子提供构象刚度，从而降低了构象熵的代价。季碳是天然产物结构的主要特征，并且与具有高sp ²计数的平面化合物相比，已与更有效和选择性地结合至目标蛋白质有关。季碳立体中心的存在允许探索新的化学空间以获得具有增强的三维性的新分子。这些特征，加上对开发sp ^3的认识不断提高丰富的分子，提高了季碳立体中心在生物活性化合物中的应用。希望该《观点》能够激发化学家利用季碳立构中心提高效力，选择性和其他类似药物的特性。

更新日期：2020-08-17

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