ATP citrate lyase (ACLY) is an important metabolic enzyme involved in the synthesis of fatty acid and cholesterol. The inhibition of ACLY is considered as a promising therapeutic strategy for various metabolic diseases and numerous malignancies. In this study, a novel macrocyclic compound 2 has been identified as a potent ACLY inhibitor with the "ring closing" strategy for conformational restriction based on NDI-091143. It showed potent ACLY inhibitory activity and binding affinity comparable to the positive control. Furthermore, compared with the positive control (T 1/2 = 3.36 min), the metabolic stability of 2 in HLMs (T 1/2 = 531.22 min) was significantly improved. All of these results characterized 2 as a promising lead compound worthy of further study
A series of indole-fused scaffolds and derivatives was synthesized by cyclization reaction of 2-indolylmethanols with azonaphthalene. These reactions were realized under mild reaction conditions through catalyst control, providing structurally diverse...
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