Synthesis of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines as potent inhibitors of Mycobacterium tuberculosis

A series of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines 7a–p was designed and synthesized from 2-acetyl thiophene in six step reaction sequence involving modified Bohlmann-Rahtz and Vilsmeier-Haack-Arnold reactions as key transformations....

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2019-02, Vol.164, p.171-178
Main Authors: Marvadi, Sandeep Kumar, Krishna, Vagolu Siva, Sriram, Dharmarajan, Kantevari, Srinivas
Format: Article
Language:English
Subjects:
Mycobacterium tuberculosis
Piperazine
Quinoline
Thiophene
Vilsmeier-Haack-Arnold reaction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines 7a–p was designed and synthesized from 2-acetyl thiophene in six step reaction sequence involving modified Bohlmann-Rahtz and Vilsmeier-Haack-Arnold reactions as key transformations. 2-(Thiophen-2-yl)dihydroquinoline was formylated and subsequently chlorinated using DMF-POCl3. The resulting aldehyde was reduced to give an alcohol and then converted to bromide using PBr3. Further coupling of bromide with morpholine, thiomorpholine and N-substituted piperazines resulted in the desired quinolines 7a-p in very good yields. All the new derivatives 7a–p were characterized by their NMR and mass spectral analysis. In vitro screening of new compounds for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), resulted in two derivatives 7f and 7p as most potent antitubercular agents (MIC:1.56 μg/mL) with lower cytotoxicity profiles. [Display omitted] •A series of novel 2-thiophenyl dihydroquinoline derivatives were designed and synthesized.•Morpholine, Thiomorpholine and N-substituted piperazines were coupled to quinoline core.•7f &7p showed most potent in vitro antitubercular activity (MIC: 1.56 μg/mL) & low cytotoxicity.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2018.12.043