Synthesis of 1,2,4-Oxadiazin-5(6H)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors
Presnukhina S.I. Kotlyarova V.D. Shetnev A.A. Baykov S.V. Turmanov R. Appazov N. Zhapparbergenov R. Zhussupova L. Togyzbayeva N. Cloete S.J. Korsakov M.K. Boyarskiy V.P. Petzer A. Petzer J.P.
December 2024Multidisciplinary Digital Publishing Institute (MDPI)
Molecules
2024#29Issue 23
Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6H)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6H)-ones. The results of the in vitro MAO inhibition studies showed that the 1,2,4-oxadiazin-5(6H)-ones were indeed inhibitors of human MAO with the most potent inhibition observed for 5f (IC50 = 0.900 µM) and 7c (IC50 = 0.371 µM). It was concluded that, with appropriate substitution, 1,2,4-oxadiazin-5(6H)-one derivatives would act as good potency MAO-B inhibitors and lead compounds for the development of antiparkinsonian drugs. In Parkinson’s disease, MAO-B inhibitors enhance central dopamine levels and reduce MAO-mediated production of hydrogen peroxide and resultant oxidative injury. This study represents one of few works to investigate synthetic approaches and biological activities of the 1,2,4-oxadiazin-5(6H)-one class of heterocycles.
inhibition , MAO , monoamine oxidase , oxadiazine , Parkinson’s disease
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Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, Saint Petersburg, 199034, Russian Federation
Pharmaceutical Technology Transfer Centre, Yaroslavl State Pedagogical University Named after K.D. Ushinsky, Respublikanskaya St., 108, Yaroslavl, 150000, Russian Federation
Laboratory of Engineering Profile “Physical and Chemical Methods of Analysis”, Korkyt Ata Kyzylorda University, 29 Aiteke Bi Str., Kyzylorda, 120014, Kazakhstan
Moscow Center for Advanced Studies, 20, Kulakova Str., Moscow, 123592, Russian Federation
“DPS Kyzylorda” LLP, Amangeldy Imanov Str., 112A, Kyzylorda, 120008, Kazakhstan
CNEC” LLP, Dariger Ali Lane, 2, Kyzylorda, 120001, Kazakhstan
Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, 2520, United States
Institute of Chemistry
Pharmaceutical Technology Transfer Centre
Laboratory of Engineering Profile “Physical and Chemical Methods of Analysis”
Moscow Center for Advanced Studies
“DPS Kyzylorda” LLP
CNEC” LLP
Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences
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