Poudapally Suresh, Battu Shankar, Velatooru Loka Reddy, Bethu Murali Satyanarayana, Janapala Venkateswara Rao, Sharma Somesh, Sen Subhabrata, Pottabathini Narender, Iska Vijaya Bhaskara Reddy, Katangoor Vidya
Medicinal Chemistry Division, GVK Biosciences Pvt. Ltd, Plot 28A, IDA Nacharam, Hyderabad, India; JNTUH-College of Engineering, Nachupally, Karimnagar, India.
Medicinal Chemistry Division, GVK Biosciences Pvt. Ltd, Plot 28A, IDA Nacharam, Hyderabad, India.
Bioorg Med Chem Lett. 2017 May 1;27(9):1923-1928. doi: 10.1016/j.bmcl.2017.03.042. Epub 2017 Mar 18.
A robust economic approach to N-(quinazoline-4-yl)sulfonamides was developed and synthesized different aryl, hetero aryl, alkyl and cyclopropyl sulfonamides in excellent yields. All the compounds were evaluated for cytotoxic affinity to SKOV3, DU145, THP1, U937, and COLO205 cell lines. Interesting to find that the bulkiness of substituent at C-2 position of quinazoline forces the molecule to flip around in order to bind in the active site, when compared to the binding preference of previously known quinazoline compounds. Among the 21 compounds synthesized 2b, 2d, 2e, 2h, 2i, 3c, 3d, 3f, 3g and 3h found to be active on all the cell lines tested with IC values <10µg/mL. Performed docking simulations to understand the binding preference of various C-2 substituted quinazoline sulfonamides.
开发了一种用于 N-(喹唑啉-4-基)磺酰胺的稳健经济方法，并以优异产率合成了不同的芳基、杂芳基、烷基和环丙基磺酰胺。对所有化合物进行了对 SKOV3、DU145、THP1、U937 和 COLO205 细胞系的细胞毒性亲和力评估。有趣的是，与先前已知的喹唑啉化合物的结合偏好相比，喹唑啉 C-2 位取代基的体积迫使分子翻转以结合到活性位点。在合成的 21 种化合物中，发现 2b、2d、2e、2h、2i、3c、3d、3f、3g 和 3h 对所有测试细胞系均有活性，IC 值 <10µg/mL。进行对接模拟以了解各种 C-2 取代喹唑啉磺酰胺的结合偏好。
