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

GÜNDÜZ, MİYASE GÖZDE; ŞAFAK, OSMAN CİHAT; EL-KHOULY, Ahmed; SARA, MEHMET YILDIRIM; ÖZER, Erdem Kamil; Simsek, Rahime; İSKİT, ALPER BEKTAŞ

doi:10.1515/tjb-2016-0247

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

Erdem Kamil ÖZER, (Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, Turkey)

Miyase Gözde GÜNDÜZ, (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey)

Ahmed EL-KHOULY, (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey)

MEHMET YILDIRIM SARA, (Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey)

Rahime ŞİMŞEK, (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey)

Alper Bektaş İSKİT, (Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey)

OSMAN CİHAT ŞAFAK (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey)

Türk Biyokimya Dergisi

2 0

Yıl: 2018 Cilt: 43 Sayı: 6 Sayfa Aralığı: 578 - 586 Metin Dili: İngilizce DOI: 10.1515/tjb-2016-0247 İndeks Tarihi: 09-10-2019

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

Öz:

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.

Anahtar Kelime:

Konular: Diş Hekimliği Toksikoloji Biyokimya ve Moleküler Biyoloji Farmakoloji ve Eczacılık

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

Öz:

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.

Anahtar Kelime:

Konular: Diş Hekimliği Toksikoloji Biyokimya ve Moleküler Biyoloji Farmakoloji ve Eczacılık

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	ÖZER E, GÜNDÜZ M, EL-KHOULY A, SARA M, Simsek R, İSKİT A, ŞAFAK O (2018). Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. , 578 - 586. 10.1515/tjb-2016-0247
Chicago	ÖZER Erdem Kamil,GÜNDÜZ MİYASE GÖZDE,EL-KHOULY Ahmed,SARA MEHMET YILDIRIM,Simsek Rahime,İSKİT ALPER BEKTAŞ,ŞAFAK OSMAN CİHAT Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. (2018): 578 - 586. 10.1515/tjb-2016-0247
MLA	ÖZER Erdem Kamil,GÜNDÜZ MİYASE GÖZDE,EL-KHOULY Ahmed,SARA MEHMET YILDIRIM,Simsek Rahime,İSKİT ALPER BEKTAŞ,ŞAFAK OSMAN CİHAT Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. , 2018, ss.578 - 586. 10.1515/tjb-2016-0247
AMA	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. . 2018; 578 - 586. 10.1515/tjb-2016-0247
Vancouver	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. . 2018; 578 - 586. 10.1515/tjb-2016-0247
IEEE	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O "Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers." , ss.578 - 586, 2018. 10.1515/tjb-2016-0247
ISNAD	ÖZER, Erdem Kamil vd. "Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers". (2018), 578-586. https://doi.org/10.1515/tjb-2016-0247

APA	ÖZER E, GÜNDÜZ M, EL-KHOULY A, SARA M, Simsek R, İSKİT A, ŞAFAK O (2018). Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi, 43(6), 578 - 586. 10.1515/tjb-2016-0247
Chicago	ÖZER Erdem Kamil,GÜNDÜZ MİYASE GÖZDE,EL-KHOULY Ahmed,SARA MEHMET YILDIRIM,Simsek Rahime,İSKİT ALPER BEKTAŞ,ŞAFAK OSMAN CİHAT Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi 43, no.6 (2018): 578 - 586. 10.1515/tjb-2016-0247
MLA	ÖZER Erdem Kamil,GÜNDÜZ MİYASE GÖZDE,EL-KHOULY Ahmed,SARA MEHMET YILDIRIM,Simsek Rahime,İSKİT ALPER BEKTAŞ,ŞAFAK OSMAN CİHAT Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi, vol.43, no.6, 2018, ss.578 - 586. 10.1515/tjb-2016-0247
AMA	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi. 2018; 43(6): 578 - 586. 10.1515/tjb-2016-0247
Vancouver	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers. Türk Biyokimya Dergisi. 2018; 43(6): 578 - 586. 10.1515/tjb-2016-0247
IEEE	ÖZER E,GÜNDÜZ M,EL-KHOULY A,SARA M,Simsek R,İSKİT A,ŞAFAK O "Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers." Türk Biyokimya Dergisi, 43, ss.578 - 586, 2018. 10.1515/tjb-2016-0247
ISNAD	ÖZER, Erdem Kamil vd. "Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers". Türk Biyokimya Dergisi 43/6 (2018), 578-586. https://doi.org/10.1515/tjb-2016-0247