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.
| Original language | English (US) |
|---|---|
| Article number | 129329 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 90 |
| DOIs | |
| State | Published - Jun 15 2023 |
Funding
We are grateful for the generous support from the National Institutes of Health for R.B.S (R35GM131788). S.Y received funding from Chapman University Office of Research (Faculty Opportunity Grant). This work made use of the IMSERC at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633); the State of Illinois and International Institute for Nanotechnology (IIN). We also thank the core labs at the Chapman University School of Pharmacy for access to all instrumentation.
Keywords
- Enzyme Inhibitor
- Improved synthesis
- Inhibition of cancers
- Neuronal nitric oxide synthase
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
