Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor.
Basic Information
ID: ALA5247665
Journal: Bioorg Med Chem Lett
Title: Improved synthesis and anticancer activity of a potent neuronal nitric oxide synthase inhibitor.
Authors: Vasu D, Reidl CT, Wang E, Yang S, Silverman RB.
Abstract: An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that were reported in the previous report. Compound 1, which previously was shown to inhibit IFN-γ-induced tumor growth in a human melanoma xenograft mouse model, was found to inhibit the growth of metastatic melanoma, glioblastoma, and hepatocellular carcinoma in vitro.
CiteXplore: 37196870
DOI: 10.1016/j.bmcl.2023.129329
Patent ID: ┄