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A Novel Synthesis of the NAMPT Inhibitor FK866

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DOI: 10.23977/analc.2023.020117 | Downloads: 12 | Views: 415

Author(s)

Peifeng Zhang 1, Defeng Xu 1

Affiliation(s)

1 School of Pharmacy, Changzhou University, Changzhou, 213164, China

Corresponding Author

Defeng Xu

ABSTRACT

In this article, we report a safe and high-yield synthesis method for the NAMPT inhibitor FK866, which avoids the use of flammable lithium aluminum hydride and highly toxic sodium azide, and the synthesis of key intermediates by the Gabrielle synthesis method to construct the amino group in 33% total reaction yield, which is a twofold increase in yield compared with existing synthesis methods, and enhances the safety of the synthesis method. Nicotinamide adenine dinucleotide (NAD) is an important cofactor in life's energy metabolism, regulating redox-related proteins such as cellular respiration, glycolysis, citric acid cycle, cell communication, transcriptional regulation, post-translational protein modification, and oxidative phosphorylation in cellular respiration. NAD is a core coenzyme of metabolism, mainly involved in redox reactions, but also in post-translational modifications to regulate DNA damage responses or gene expression, as a substrate for poly ADP ribose polymerase (PARP) and deacetylating Sirtuins. In cells, a specific set of synthases regulates the three major biosynthetic pathways of NAD, including the quinolinic acid phosphotransferase (QAPRT)-mediated ab initio synthesis, the nicotinic acid phosphoribosyltransferase (NAPRT)-mediated preprocessor (PH) synthesis pathway, and the NAMPT-mediated salvage pathway. Therefore, enzymes involved in NAD metabolism are attractive targets for drug discovery.

KEYWORDS

NAMPT inhibitor, FK866, synthesis method

CITE THIS PAPER

Peifeng Zhang, Defeng Xu, A Novel Synthesis of the NAMPT Inhibitor FK866. Analytical Chemistry: A Journal (2023) Vol. 2: 131-137. DOI: http://dx.doi.org/10.23977/analc.2023.020117.

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