Synthesis and antisecretory and antiulcer activities of derivatives and analogs of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide

Abstract

New thioamide derivatives of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (29) and related compounds (in which the tetrahydrothiophene ring was replaced by tetrahydrothiopyran, tetrahydrofuran, 1,3-dithiane, or 1,3-oxathiane and where the pyridine ring was replaced by other nitrogen heterocycles) were synthesized and tested for their antisecretory and antiulcer activities. These thioamides were prepared according to one of the following methods: reaction of an isothiocyanate with the carbanion of the corresponding cyclic precursor (for secondary thioamides); reaction of ammonia or an amine with the dithio ester prepared from the same precursor (for primary, secondary, and tertiary thioamides). These thioamides were evaluated by the Shay method to measure their antisecretory activity and by the stress-induced-ulcer method to test their antiulcer activity. Structure-activity relationships are discussed. N-Methyl-2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (R.P. 40749, 30) exhibited activities that were at least 10 times higher than those reported for cimetidine.

Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes

“…Prepared according to a modified previously reported method. 38 Freshly distilled picolinaldehyde (1 mL, 10.51 mmol, 1 equiv) and 1,3-propanedithiol (1.16 mL, 11.56 mmol, 1.1 equiv) were dissolved in DCE (20 mL). p -Toluenosulfonic acid (200 mg, 1.05 mmol, 0.1 equiv) was added to the mixture and the solution refluxed for 24 h. The reaction was cooled to room temperature and quenched with a 10% aqueous NaOH solution (10 mL).…”

“…The solvent was evaporated and the product isolated by flash chromatography (Hex:AcOEt, 70:30) to give 4i as a yellow solid in 54% yield (1.111 g, 5.63 mmol), with same spectral characterization as previously described. 38 1 H NMR (300 MHz, CDCl 3 ) δ ppm 8.57 (dd, J = 4.4, 1.5 Hz, 1H), 7.67 (td, J = 7.6, 1.8 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.22–7.18 (m, 1H), 5.35 (s, 1H), 3.11–2.92 (m, 4H), 2.23–2.13 (m, 1H), 2.05–1.90 (m, 1H).…”

The reaction of carbon disulphide with α-haloketones and primary amines in the presence of potassium iodide as catalyst

“…Its derivatives have showed antisecretory and antiulcer activities. 16 Because of the potential use of thiophenes and annulated thiophenes as pharmaceuticals, conjugated polymers, organic conductors, semiconductors and light emitting devices, their synthesis are of special interest. [17][18][19][20][21][22] Alkylation of an intermediate dimetaloketene dithioacetal is a general strategy employed for the synthesis of alkylthiothiophenes or thienothiophenes.…”

Diastereoselective synthesis and 1H and 13C NMR study of 4‐acetyl‐2,6‐diaroyl‐3,5‐diaryl‐4‐ethoxycarbonylthiane‐1,1‐dioxides

“…To mention a few applications, they are used as anti-inflammatory, 1,2 antihypertensive, 3 antiulcer, 4 antimicrobial 5 and antitumour 6 agents. The synthesis of thianes assumes further importance in view of (i) their non-existence in nature and (ii) a renewed interest in their synthesis.…”