Synthesis of halogen-substituted 1,5-benzothiazepine derivatives and their vasodilating and hypotensive activities

Abstract

In an attempt to improve the effectiveness and duration of the action of diltiazem (1), a 1,5-benzothiazepine calcium channel blocker, its derivatives (2) with halogen substituents on the fused benzene ring were synthesized. These compounds were evaluated for their effects on vertebral and coronary blood flows and antihypertensive activity. The structure-activity relationships are discussed. The 8-chloro derivative ((+)-2b), the most potent compound in this series, was selected for clinical evaluation as a cerebral vasodilating and antihypertensive agent.

Amidation of Aldehydes and Alcohols through α‐Iminonitriles and a Sequential Oxidative Three‐Component Strecker Reaction/Thio‐Michael Addition/Alumina‐Promoted Hydrolysis Process to Access β‐Mercaptoamides from Aldehydes, Amines, and Thiols

“…www.chemeurj.org ed into their corresponding amides with cyclopropylamine, 4-methoxyaniline, and phenethylamine as reaction partners ( Thio-Michael addition of a,b-unsaturated-a-iminonitriles and subsequent hydrolysis into b-mercaptoamides: Mercaptoamides hold a special interest in medicinal chemistry owing to their presence in a number of bioactive compounds [35] that show anti-inflammatory, [36] antiviral and antifungal, [37] antipsychotic, [38] antihypertensive, [39] and anginarelieving activities, etc. [40] The thio-Michael addition reaction is obviously one of the most direct ways to make this family of compounds and both metal-and organocatalyzed Michael additions of thiols to a,b-unsaturated carbonyl compounds are well documented.…”

Plant Assisted Zinc Oxide Nano-Particles for Synthesis of 1, 5-Benzothiazepines

“…Two α, β-unsaturated carbonyl groups at ortho and para position of -OH group in bis-chalcones were converted into 1,5-benzothiazepine rings by cyclocondensation reaction of bis-chalcones (1-9) (10 mmol) with 2-aminobenzenethiol (10 mmol) using plant assisted zinc oxide nanoparticles as catalyst. Formation of desired compounds (1-9) were confirmed by IR, 1 H NMR, 13 C NMR, IR spectrum of compound displayed band around 300 cm -1 for -OH stretching of phenolic ring, band at 1500 cm -1 for C=N stretching and band at 820, 756 cm -1 for C-S stretching clearly reflecting the formation the formation of desired product. Presence of two 1,5benzothiazepine rings, one at ortho and second at para position of -OH group in phenol was clearly indicated by the 1 H NMR spectra, for example, in 1 H NMR spectrum of compounds 1,5-benzothiazepine ring at para position of -OH in phenol displayed two doublet of doublet peaks for methylene and methine protons at δ 3.12 and δ 5.32 whereas 1,5-benzothiazepine ring at ortho position of -OH in phenol displayed two doublet of doublet peaks for methylene and methine protons at δ 3.57 and δ 5.48.…”

“…Now a day's 1,5benzothiazepines are being used as calcium antagonists and coronary vasodilators, as antidepressants. The 1,5-benzothiazepine moiety is important class of pharmacophore, as compounds bearing this structural unit possess very broad spectrum of biological activities such as anticonvulsant,1 Ca +2 channel antagonist,2 anti-anginal,3 anti HIV,4 1,5 antimicrobial 5 ,antifungal 6 ,antihypertensive 7 , anticancer 8 , antiarrhythmic 9 , anti-inflammatory 10 , coronary vasodilatory 11 , anticonvulsant 12 , CNS depressant 13 , anti-HIV 14 etc. Number of different methods have been reported for the synthesis of 1, 5benzothiazepines 15 .Very common used method involves the reaction of 2-aminobenzenethiol with α, β-unsaturated carbonyl compounds i.e.…”

Sustainable Catalytic Process with a High Eco‐Scale Score for the Synthesis of Five‐, Six‐, and Seven‐Membered Heterocyclic Compounds Using Nanocrystalline Zeolites

“…1,5‐Benzoheteroazepines are nitrogen‐ and sulfur‐containing seven‐membered heterocyclic compounds that exhibit a broad range of interesting biological activities, and numerous drug molecules have been developed based on 1,5‐benzothiazepines (Scheme ). For example, 1,5‐benzothiazepine‐based compounds have been reported to exhibit Ca 2+ channel antagonistic activity, CNS depressant activity, antiplatelet aggregator activity, anticancer activity, anti ‐HIV activity, antimicrobial activity, cardiovascular activity, and cholinesterase inhibitory activity . 1,5‐Benzodiazepines (seven‐membered heterocyclic compounds containing two nitrogen atoms) are widely used as anticonvulsant, anti‐anxiety, sedative, and antidepressants .…”