Theoretical design of new indole-3-carboxamide derivatives as renin inhibitors

Mota, Estella G. da; Duarte, Mariene Helena; Cunha, Elaine F. F. da; Freitas, Matheus P.

doi:10.1007/s00044-015-1362-4

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…However, many computational and theoretical studies have been conducted by researchers to study and design indole 3-carboxamide derivatives, the results of which confirm previous studies [62,63]. In recent years, indole derivatives are shown to be active against many enzymes Renin [56] and proteins, indicating that these compounds are still in research [64][65][66][67].…”

Section: Renin Inhibitorssupporting

confidence: 75%

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Chehardoli

Bahmani

2020

Mol Divers

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Indole derivatives have been the focus of many researchers in the study of pharmaceutical compounds for many years. Researchers have investigated the effect of carboxamide moiety at positions 2 and 3, giving unique inhibitory properties to these compounds. The presence of carboxamide moiety in indole derivatives causes hydrogen bonds with a variety of enzymes and proteins, which in many cases, inhibits their activity. In this review, synthetic strategies of indole 2 and 3-carboxamide derivatives, the type, and mode of interaction of these derivatives against HLGP, HIV-1, renin enzyme, and structure-activity studies of these compounds were investigated. It is hoped that indole scaffolds will be tested in the future for maximum activity in pharmacological compounds.

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Section: Renin Inhibitorssupporting

confidence: 75%

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Chehardoli

Bahmani

2020

Mol Divers

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“…45 indole-3-carboxamide compounds reported for renin inhibitory activity were considered for this study [14]. The potency of indole-3-carboxamide derivatives for eliciting renin inhibition was expressed as IC 50 (half maximal inhibitory concentration) values.…”

Section: Datasetmentioning

confidence: 99%

Combined Ligand and Structure Based Approaches Towards Developing Novel Renin Inhibitors for the Treatment of Hypertension

Unni¹,

Lulu²,

Pillai³

2021

Preprint

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Hypertension is considered as the predominant risk factor for the onset of Cardiovascular disease (CVD) in the elder population. The chronic activation of Renin Angiotensin System (RAS) is considered as the primary causative factor for the inception of hypertension in geriatric population. Angiotensin Converting Enzyme (ACE) is a highly explored druggable target in the context of hypertension since this enzyme catalyses the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. But clinical trials conducted on ACE inhibitors reported their incompetence in the effective treatment of hypertension. Hence, recent studies are focussing on renin, which is a central component of RAS in the regulation of blood pressure. The present study focuses on the elucidation of physicochemical properties of chemical compounds essential for renin inhibition and identification of novel renin inhibitors possessing enhanced potency as well as bioavailability. We have employed Molecular Field Topology Analysis (MFTA) as well as Structure Based Drug Design (SBDD) approaches for the accomplishment of above-mentioned objectives. MFTA approach were piloted on 45 indole-3-carboxamide derivatives by elucidating the significance of charge distribution as well as molecular size of chemical species in eliciting renin inhibition. Optimal model was obtained with Nf = 3, r2 = 0.81 , Q2 = 0.65. Molecular docking, atom-based binding free energy contributions and bioavailability assessments were carried out to identify most potent lead molecule among 45 compounds reported for renin inhibition. Further, new derivative molecules were predicted for the best lead molecule by employing chemical space exploration. All datasets, descriptor values, QSAR models for predictions usage and plots will be available in <a href="https://github.com/giribio/agingdata">https://github.com/giribio/agingdata</a>

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Iron(III)‐Catalyzed 1,3‐Functional Group Transposition Reactions: Synthetic Protocol to Access 3‐Substituted Indoles

Wei

Shi

2016

Asian J Org Chem

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An iron(III)-catalyzed 1,3-dihydroisobenzofuran transferring reaction of indoles provides ap ractical synthetic protocol to access 3-substitutedi ndolesu nder mild conditions. This is the first example of a1 ,3-functional group transposition of a N-protected indole to give a3 -substituted indole derivative in good yield. Ap lausible mechanism has been proposed on the basis of deuterium-labeling and control experiments. Furthermore, after as imple oxidation, the obtained product could be easily transformed into 3-phthalide indole, ad rug candidate for treating Alzheimer'sd isease.The indole core is av ery common structuralm otif found in natural products and medicines.[1] Research on the indole alkaloids' biological activities and investigations into indole'sr eactivities have been carriedo ut extensively.[2] The natural products or drugs bearingi ndole cores often have remarkable bioactivities. For example, bioactivity studies showed that dragmacidin (Scheme 1) is at ype of serine/threonine protein phosphatase inhibitor that hasa nti-herpesvirus and anti-HIV effects; indomethacin has been used as aN SAID( nonsteroidal anti-inflammatory drug) for more than fifty years; citrinalin B,atype of prenylated indole alkaloid, had its total synthesis reported recently, [1h] which may help develop ad ifferent approacht o synthesize quinineo rm orphine derivatives. Some other indole-containing compounds have been applied as neuroprotection, anti-cancer compounds, antibiotics, etc.[3] With regard to indole'sr eactivity,i ti sw ell known that the 3-position of indole has the richest electron density and that this carbon site can act as the nucleophile to allow 3-substituted indole derivatives to undergo Friedel-Crafts-type reactions.To the best of our knowledge, the synthesis of 3-substituted indoles has always been as ignificantly demanding task for organic chemists working in indole chemistry.[4] As shown in Scheme 2, the previous methods to achieve this goal include simple Friedel-Crafts-type substitution, transition-metal-catalyzed CÀHb ond activation or cross-coupling, including crossdehydrogenative couplingb yu sing the nucleophilic nature of the 3-position of the indole (Scheme 2). However, 1,3-functionScheme1.Reported indole-based structures for drugs and natural products.Scheme2.Reported methodsfor the synthesis of 3-substituted indoles.

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Theoretical design of new indole-3-carboxamide derivatives as renin inhibitors

Cited by 4 publications

References 23 publications

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review

Combined Ligand and Structure Based Approaches Towards Developing Novel Renin Inhibitors for the Treatment of Hypertension

Iron(III)‐Catalyzed 1,3‐Functional Group Transposition Reactions: Synthetic Protocol to Access 3‐Substituted Indoles

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