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4-Chloropyridine is an inhibitor of nicotinamide N-methyltransferase (NNMT). It can act as a substrate for NNMT and, during its catalytic reaction, enhances the electrophilicity of the C4 position by methylating the nitrogen atom of the pyridine ring. This promotes an aromatic nucleophilic substitution reaction with the non-catalytic cysteine (C159) in NNMT, ultimately leading to the suicide inhibition of NNMT's activity. 4-Chloropyridine holds potential for the development of NNMT activity-based probes [1].

Pour 4-chloropyridine into distilled water, and excess of 6M NaOH is added to give pH 12. The organic phase is separated and extracted with four volumes of diethyl ether. The combined extracts are filtered through paper to remove water, and the solvent is evaporated. The dark brown residual liquid is kept under high vacuum [Vaidya & Mathias J Am Chem Soc 108 5514 1986]. It can be distilled, but readily darkens and is best kept as the hydrochloride [7379-35-3] M 150.1, m 163-165o(dec). [Beilstein 20/5 V 410.]

[1] Sen S, et al. Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase. ACS Chem Biol. 2019 Apr 19;14(4):613-618. DOI:10.1021/acschembio.9b00211