Synthesis, Characterization and Anticancer Activity of 5-Substituted 4,5,6,7-Tetrahydro- N-(tetrahydro-2H-pyran-4-yl)thieno[3,2-c]pyridine-2-carboxamide Derivatives

Abstract

4,5,6,7-Tetrahydrothieno pyridine (THTP) and their derivatives are an important heterocyclic compounds that exhibits various biological activities viz.,antimicrobial activity, antileishmanial activity, antiarrhythmic activity, antiinflammatory activity, antihyperlipidemic activity, antidepressant activity, anticancer activity, antiplatelet activity and antidiabetic etc. The present study describes the synthesis, characterization and in vitro cytotoxic potential against human lung carcinoma of some novel derivatives of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (7A-M) with benzylic and amide substitution on the nitrogen atom of tetrahydro theino pyridine ring. The synthetic steps involves (i) Vilsmeyer protocol in step 1 (ii) formation of tetrahydothieno[3,2-c]pyridine ring in presence of 2-mercaptoacetate in step 2 (iii) alkaline hydrolysis followed by amide coupling with tetrahydro-2H-pyran-4-amine in step 3 and step 4. The newly synthesized compounds 7A-M was sufficiently characterized by 1 H NMR, IR and mass techniques. Furthermore, these derivatives were screened for their in vitro cytotoxic potential against human lung carcinoma (HCT-116) cell line using the MTT assay. Compound 7B (IC50: 69.52 µg) and compound 7K (IC50: 66.35 µg) exhibited significant activity at micro molar concentration when compared to standard drug camptothecin.This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which allows others to copy and redistribute the material in any medium or format, remix, transform, and build upon the material, as long as appropriate credit is given and the new creations are licensed under the identical terms. tert-Butyl 3-formyl-4-oxopiperidine-1-carboxylate (2):To a stirred solution of tert-butyl 4-oxopiperidine-1-carboxylate (1) (40 g, 0.20 mol) in dichloromethane (500 mL) was added DMF (30.9 mL, 0.40 mol) followed by POCl3 (30 mL, 0.32 mol) at 0 °C and the reaction mixture was stirred at room temperature for 4 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with aqueous sodium acetate solution (at 0 °C), diluted with water and extracted with ethyl acetate (2 × 100 mL). The organic layer was washed with water (3 × 50 mL), brine solution, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to obtain compound 2. The crude compound was used in the next step without any purification. Yellow oil; Yield: 30 g, 65 %; Elemental analysis, C11H17NO4, calcd. (found) %: C 58.14 (58.11), H 7.54 (7.56), N 6.16 (6.12). IR (KBr, νmax, cm -1 ): 2926 (-CH str.), 1695, 1635 (-C=O str.), 1122 (-C-OCstr.); 1 H NMR (500 MHz, CDCl3) δ: 10.14 (s, 1H), 4.15 (d, J = 7.0 Hz, 2H), 3.72 (t, J = 6.0 Hz, 2H), 2.44 (t, J = 6.0 Hz, 2H), 2.09 (brs, 2H), 1.45 (s, 9H); MS: calcd. for C15H21NO4S [m/z] 311.40; found: 312.6 [M+H] + . 5-tert-Butyl 2-ethyl-6,7-dihydrothieno[3,2-c]pyridine-2,5-(4H)-dicarboxylate (3):To a stirred solution of compound 2 (30 g, 0.13...

Preparation and characterization of chalcone compounds.

“…The carbonyl, the alkene double bond adjacent to the carbonyl appears in two positions (E)Trans and (Z)Cis. (2) Figure (1-1): represents the structure of the chalcone Presence of the effective group ( ) In the composition of chalcone, it has a wide range of biological activities (3) , so it occupies an important place in medical and biological chemistry because of its therapeutic properties that fight cancer and infections (4) , germs and viruses (5), antioxidants and fungi (6), combating HIV HIV, tuberculosis and tumors, as well as an analgesic (7), combating high blood pressure, irregular heartbeat, gout, combating anxiety, convulsions, obesity and combating diabetes (8,9) In addition, pyrazole, oxazoline, oxazine pyrimidine, and others are considered because they contain successive double bonds that lead to delocalization of electrons by π, and this reduces their electrophilic property When chalcones interact with reagents searching for the nucleus to (10). prepare heterogeneous cyclic compounds, they act as a reagent searching for electrons according to Michael's addition reaction, where in the cyclocondensation reaction the chalcones act as a binary detector searching for electrons interacting with a binary detector searching for the nucleus as in the general equation below (2 -1).…”

Thermoacoustic Parameters of Some Liquid Mixtures of O-chloroaniline with F, NMF and N, N-DMF

“…The speed of sound (U) density (ρ) and viscosity (η) of binary or ternary liquids are indispensable in most fluid mechanics, solution theory, molecular thermodynamics, and various methodical uses. [1][2][3][4][5] These values carry a significant role to elucidate the behavior of liquids and their mixtures. 6,7 The analysis of excess functions and deviations from ideality is essential to interpret the interactions in the mixing process.…”