Synthesis of Novel Benzo[ b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors

Larisa N Kulikova; Ghulam Reza Raesi; Daria D Levickaya; Rosa Purgatorio; Gabriella La Spada; Marco Catto; Cosimo D Altomare; Leonid G Voskressensky

doi:10.3390/molecules28041662

Synthesis of Novel Benzo[ b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors

Molecules. 2023 Feb 9;28(4):1662. doi: 10.3390/molecules28041662.

Authors

Larisa N Kulikova¹, Ghulam Reza Raesi¹, Daria D Levickaya¹, Rosa Purgatorio², Gabriella La Spada², Marco Catto², Cosimo D Altomare², Leonid G Voskressensky¹

Affiliations

¹ Organic Chemistry Department, Peoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6., 117198 Moscow, Russia.
² Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.

Abstract

In this work, 2-alkyl-10-chloro-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines were obtained and their reactivity was studied. Novel derivatives of the tricyclic scaffold, including 1-phenylethynyl (5), 1-indol-3-yl (8), and azocino[4,5-b]quinoline (10) derivatives, were synthesized and characterized herein for the first time. Among the newly synthesized derivatives, 5c-h proved to be MAO B inhibitors with potency in the low micromolar range. In particular, the 1-(2-(4-fluorophenyl)ethynyl) analog 5g achieved an IC₅₀ of 1.35 μM, a value close to that of the well-known MAO B inhibitor pargyline.

Keywords: Alzheimer’s disease; MAO inhibitors; activated alkynes; benzonaphthyridine.

MeSH terms

Monoamine Oxidase / metabolism
Monoamine Oxidase Inhibitors* / pharmacology
Naphthyridines
Pargyline*
Structure-Activity Relationship

Substances

Monoamine Oxidase Inhibitors
Pargyline
Monoamine Oxidase
Naphthyridines

Grants and funding

C.D.A., M.C., and R.P. acknowledge the financial support of the Italian Ministry of Education, Universities and Research (PRIN, Grant 201744BNST_004).