Microwave-Assisted Synthesis and Spasmolytic Activity of 4-Indolylhexahydroquinoline Derivatives

El-Khouly, Ahmed; Gündüz, Miyase Gözde; Cengelli, Cigdem; Şimşek, Rahime; Erol, Kevser; Şafak, Cihat; Yıldırım, Sema Öztürk; Butcher, Raymond J.

doi:10.1055/s-0033-1348261

Cited by 6 publications

(2 citation statements)

References 9 publications

(12 reference statements)

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“…It has been demonstrated in the past that the substitution at the hexahydroquinoline ring’s six-position affects the sensitivity of the L-type channel inhibition [ 23 ]. Moreover, the substitution with simple phenyl rings are preferred over aromatic systems with heteroatoms due the animal toxicity [ 24 , 25 ]. Additionally, the analogs have exposed that the biological activity depends on the hydrophilic, lipophilic, electronic and steric properties of the substituents [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers

et al. 2023

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Pyrimidines play an important role in modern medical fields. They have a wide spectrum of biological activities such as antimicrobial, anticancer, anti-allergic, anti-leishmanial, antioxidant agents and others. Moreover, in recent years, 3,4-dihydropyrimidin-2(1H)ones have attracted researchers to synthesize them via Biginelli reaction and evaluate their antihypertensive activities as bioisosters of Nifedipine, which is a famous calcium channel blocker. Our new target compounds were prepared through one-pot reaction of thiourea 1, ethyl acetoacetate 2 and/or 1H-indole-2-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde, 3a–c in acid medium (HCl) yielding pyrimidines 4a–c, which in turn were hydrolyzed to carboxylic acid derivatives 5a–c which were chlorinated by SOCl2 to give acyl chlorides 6a–c. Finally, the latter were reacted with some selected aromatic amines, namely, aniline, p-toluidine and p-nitroaniline, producing amides 7a–c, 8a–c, and 9a–c. The purity of the prepared compounds was examined via TLC monitoring, and structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The in vivo evaluation of the antihypertensive activity revealed that compounds 4c, 7a, 7c, 8c, 9b and 9c had comparable antihypertensive properties with Nifedipine. On the other hand, the in vitro calcium channel blocking activity was evaluated by IC50 measurement and results revealed that compounds 4c, 7a, 7b, 7c, 8c, 9a, 9b, and 9c had comparable calcium channel blocking activity with the reference Nifedipine. Based on the aforementioned biological results, we selected compounds 8c and 9c to be docked onto Ryanodine and dihydropyridine receptors. Furthermore, we developed a structure–activity relationship. The designed compounds in this study show promising activity profiles in reducing blood pressure and as calcium channel blockers, and could be considered as new potential antihypertensive and/or antianginal agents.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers

et al. 2023

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“…These compounds were synthesized by the reaction of 1,3-cyclohexanediones, functionalized indole carboxaldehyde derivative, alkyl acetoacetate and NH 4 OAc in MeOH via a modified Hantzsch reaction (Scheme 23). [133] This method demonstrate an effective and useful approach for the synthesis of diverse 1,4-DHPs under MWI and also examine the effect of functionalized cyclohexane ring fused to the DHP ring in combination with indole scaffold on the 1,4-DHP framework.…”

Section: Chemistryselectmentioning

confidence: 96%

Construction and Aromatization of Hantzsch 1,4‐Dihydropyridines under Microwave Irradiation: A Green Approach

Heravi

Zadsirjan

2022

ChemistrySelect

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Hantzsch reaction, leading to the synthesis of 1,4-dihydropyridines (1,4-DHPs) with momentous biological activities and pharmacological properties is a well-known MCR. In recent years, microwave irradiation (MWI) has been successfully used as the unconventional and green source of energy to promote organic transformations including Hantzsch 1,4-dihydropyri-dines. Literature survey disclosed that construction of 1,4-DHPs as well as their aromatization can be successfully performed under MWI in solution as well as in dry media. In this review, we try to underscore recent advances in the synthesis and aromatization of Hantzsch 1,4-DHPs under MWI as green approach.

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5-Oxo-hexahydroquinoline: an attractive scaffold with diverse biological activities

et al. 2018

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Microwave-Assisted Synthesis and Spasmolytic Activity of 4-Indolylhexahydroquinoline Derivatives

Cited by 6 publications

References 9 publications

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Pyrimidine Derivatives as Potential Calcium Channel Blockers

Construction and Aromatization of Hantzsch 1,4‐Dihydropyridines under Microwave Irradiation: A Green Approach

5-Oxo-hexahydroquinoline: an attractive scaffold with diverse biological activities

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