Novel piperazine and morpholine substituted quinolines: Selective synthesis through activation of 3,6,8-tribromoquinoline, characterization and their some metabolic enzymes inhibition potentials


Cakmak O. , Okten S., Alimli D., Ersanli C. C. , Taslimi P., KOÇYİĞİT Ü. M.

JOURNAL OF MOLECULAR STRUCTURE, vol.1220, 2020 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1220
  • Publication Date: 2020
  • Doi Number: 10.1016/j.molstruc.2020.128666
  • Title of Journal : JOURNAL OF MOLECULAR STRUCTURE
  • Keywords: Nitration, Quinoline, Piperazine substituted quinoline, Morpholine substituted quinoline, Enzyme inhibition, IN-VITRO, CRYSTAL-STRUCTURE, DERIVATIVES, ACETYLCHOLINESTERASE, CHOLINESTERASE, IDENTIFICATION, CORONAVIRUS, SAR

Abstract

Regioselective routes are described for convenient preparation of novel piperazine/morpholine substituted quinoline derivatives at C-3, C-6 and C-8 starting with 3,6,8-tribromoquinoline (6) by nucleophilic substitution via conventional heating or microwave assisted reaction conditions. 3,6,8-Tribromoquinoline (6) was treated with piperazine and morpholine under microvawe irradiation, which selectively furnished 3-mopholinyl and 3-piperazinyl quinoline derivatives 7 and 8 in yields of 58% and 60%, respectively. On the other hand, the activation of benzene cycle of quinoline by nitration of 3,6,8-tribromoquinoline, giving 5-nitro-3,6,8-tribromoquinoline (18) in quantitative yield, was enabled. Then, the bromines at C-6 and C-8 were selectively exchanged by morpholine and piperazine via SNAr reactions. Thus, 6,8-dimopholinylquinoline (22) and 5-nitro-6,8-dipiperazinylquinoline (24), biologically valuable derivatives, were prepared in high yields (82% and 72%, respectively). The synthesized compounds were fully characterizated by H-1 NMR, C-13 NMR, 2D NMR, XRD, HRMS and IR spectra. The novel molecules had effective inhibition profiles against some metabolic enzymes. Also, they have the potential of drug candidates to treat of some diseases including glaucoma, epilepsy, Alzheimer's disease (AD), leukemia, and type-2 diabetes mellitus (T2DM). (C) 2020 Elsevier B.V. All rights reserved.