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Journals / Türk Biyokimya Dergisi / 2018 / Cilt: 43 - Sayı: 6

Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers

Potansiyel kalsiyum kanal blokerleri olarak kaynaşmış 1,4-dihidropiridin türevlerinin sentezi

Cihat ŞAFAK
Yıldırım SARA
Alper Bektaş İSKİT
Rahime ŞİMŞEK
Miyase Gözde GÜNDÜZ
Erdem Kamil ÖZER
Ahmed EL-KHOULY
Pages
578–586
Publication Date
2022-11-05
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The inhibitory actionsof compounds 1–10 on calcium channel blocking activitywere tested on isolated rat aorta preparations.Results: The obtained pharmacological results showedthat although all compounds are potent relaxing agentson isolated rat aorta smooth muscle, introduction of abenzoyloxy substitiuent on the phenyl ring (compound6–10) decreased the relaxant effect of these compunds.Conclusion: The reported 1,4-DHP derivatives have calciumchannel blocking activity on rat aorta smooth muscle.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: The aim of this study was to synthesize ten1,4-dihydropyridine (DHP) derivatives in which substitutedcyclohexane rings were fused to the DHP ring andto determine how different ester groups and the benzoylsubstituent introduced in 4-phenyl ring affected theircalcium channel blocking activity.Methods: A microwave-assisted one-pot method wasapplied for the synthesis of compound 1–5 according toa modified Hantzsch reaction.
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Key Findings & Data:The benzoyl moiety wasintroduced in the 4-phenyl ring of these dihydropyridinesby refluxing with benzoyl chloride in acetone in the presenceof anhydrous potassium carbonate.
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Conclusion & Impact:The inhibitory actionsof compounds 1–10 on calcium channel blocking activitywere tested on isolated rat aorta preparations.Results: The obtained pharmacological results showedthat although all compounds are potent relaxing agentson isolated rat aorta smooth muscle, introduction of abenzoyloxy substitiuent on the phenyl ring (compound6–10) decreased the relaxant effect of these compunds.Conclusion: The reported 1,4-DHP derivatives have calciumchannel blocking activity on rat aorta smooth muscle.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objective: The aim of this study was to synthesize ten1,4-dihydropyridine (DHP) derivatives in which substitutedcyclohexane rings were fused to the DHP ring andto determine how different ester groups and the benzoylsubstituent introduced in 4-phenyl ring affected theircalcium channel blocking activity.Methods: A microwave-assisted one-pot method wasapplied for the synthesis of compound 1–5 according toa modified Hantzsch reaction. The benzoyl moiety wasintroduced in the 4-phenyl ring of these dihydropyridinesby refluxing with benzoyl chloride in acetone in the presenceof anhydrous potassium carbonate. Synthesizedproducts were characterized by elemental analysis, IR,1H-NMR and 13C-NMR spectroscopy. The inhibitory actionsof compounds 1–10 on calcium channel blocking activitywere tested on isolated rat aorta preparations.Results: The obtained pharmacological results showedthat although all compounds are potent relaxing agentson isolated rat aorta smooth muscle, introduction of abenzoyloxy substitiuent on the phenyl ring (compound6–10) decreased the relaxant effect of these compunds.Conclusion: The reported 1,4-DHP derivatives have calciumchannel blocking activity on rat aorta smooth muscle.

Özet

Amaç: Bu çalışmanın amacı, sübstitüe siklohekzan halkasının 1,4-dihidropiridin (DHP) halkasına kaynaştırıldığı on DHP türevi sentezlemek ve farklı ester grupları ile 4-fenil halkasına eklenen benzoil sübstitüentinin kalsiyum kanal bloke edici aktiviteyi ne kadar etkilediğini belirlemektir. Yöntem: 1-5 no’lu bileşiklerin sentezi için mikrodalga yardımıyla tek basamak olarak modifiye Hantzsch reaksiyonu uygulanmıştır. Benzoil grubu, bu dihidropiridinlerin 4-fenil halkasına, susuz potasyum karbonat varlığında aseton içinde benzoil klorür ile kaynatılarak sübstitüe edilmiştir. Sentezlenmiş bileşikler, eleman analizi, IR, 1H-NMR ve 13C-NMR spektroskopi ile karakterize edilmiştir. 1-10 no’lu bileşiklerin kalsiyum kanalı inhibe edici etkileri izole sıçan aort preparatları üzerinde test edilmiştir. Sonuç: Elde edilen farmakolojik sonuçlar, tüm bileşiklerin izole sıçan aort düz kasında güçlü bir gevşetici ajan olmasına rağmen, fenil halkasına (bileşik 6-10) bir benzoiloksi sübstitüentinin katılmasının, bu bileşiklerin gevşetici etkisini azalttığını göstermiştir. Tartışma: Bildirilen 1,4-DHP türevleri, sıçan aortu düz kası üzerinde kalsiyum kanal bloke edici aktiviteye sahiptir.

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Cite This Article

ŞAFAK, C., SARA, Y., İSKİT, A. B., ŞİMŞEK, R., GÜNDÜZ, M. G., ÖZER, E. K., EL-KHOULY, A. (2022). Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi, Cilt: 43 - Sayı: 6, 578–586. https://ajindex.com/articles/620999

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