Varnavas A, Lassiani L, Valenta V, Ciogli A, Gasparrini F, Mennuni L, Makovec F
Department of Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy.
Med Chem. 2005 Sep;1(5):501-17. doi: 10.2174/1573406054864070.
Starting from our lead compound, VL-0395, an anthranilic acid based CCK1 receptor antagonist, and following the well established "step by step" lead investigation strategy, we describe the final step of the anthranilic acid N-terminal optimization. Improvements for both affinity and selectivity towards CCK1 receptors have been accomplished through introduction of the fluoro substituent at C-5 and C-7 position of the indole ring together with the appropriate configuration of the aminoacidic chiral center.
从我们的先导化合物VL-0395（一种基于邻氨基苯甲酸的CCK1受体拮抗剂）出发，并遵循成熟的“逐步”先导研究策略，我们描述了邻氨基苯甲酸N端优化的最后一步。通过在吲哚环的C-5和C-7位置引入氟取代基以及氨基酸手性中心的适当构型，实现了对CCK1受体亲和力和选择性的提高。
