Gao Huai, Marhefka Craig, Jacobs Marc D, Cao Jingrong, Bandarage Upul K, Green Jeremy
Vertex Pharmaceuticals, Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
Vertex Pharmaceuticals, Incorporated, 50 Northern Avenue, Boston, MA 02210, USA.
Bioorg Med Chem Lett. 2018 Aug 15;28(15):2616-2621. doi: 10.1016/j.bmcl.2018.06.043. Epub 2018 Jun 21.
Solubilizing groups have been frequently appended to kinase inhibitor drug molecules when solubility is insufficient for pharmaceutical development. Such groups are usually located at substitution sites that have minimal impact on target activity. In this report we describe the incorporation of solubilizing groups in a class of Rho kinase (ROCK) inhibitors that not only confer improved solubility, but also enhance target potency and selectivity against a closely related kinase, PKA.
当溶解度不足以满足药物研发需求时，增溶基团常被添加到激酶抑制剂药物分子上。这类基团通常位于对靶点活性影响最小的取代位点。在本报告中，我们描述了在一类Rho激酶（ROCK）抑制剂中引入增溶基团，这些增溶基团不仅能提高溶解度，还能增强对靶点的效力以及对密切相关激酶PKA的选择性。
