Selective angiotensin II AT2 receptor agonists: Benzamide structure–activity relationships

Wallinder, Charlotta; Botros, Milad; Rosenström, Ulrika; Guimond, Marie-Odile; Beaudry, Hélène; Nyberg, Fred; Gallo‐Payet, Nicole; Hallberg, Anders; Alterman, Mathias

doi:10.1016/j.bmc.2008.05.066

Cited by 29 publications

(24 citation statements)

References 21 publications

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“…The diethyl substituted analogues are among the compounds with highest affinities in both series, which could suggest that the amide functions of the two classes of compounds interact with the same environment in the receptor. [9b]…”

Section: Resultsmentioning

confidence: 99%

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands

et al. 2014

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A novel series of ligands for the recombinant human AT2 receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)6] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with Ki values in the low micromolar range versus the recombinant human AT2 receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs.

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Section: Resultsmentioning

confidence: 99%

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands

et al. 2014

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“…However, physiological consequences of activity at other AII receptor sites, that is, AT2-AT4, especially in the context of AT1 receptor blockade and non-availability, are increasingly gaining attention and in particular vasodilation, antiproliferation and apoptosis mediated by the AT2 receptor. Interest in this potential therapeutic target is represented by the development of a series of substituted benzamide analogues and arylbenzylimidazole derivatives as selective nonpeptide AT2 receptor agonists [28,29]. AII is metabolised to AIII (Ang-(2 -8)) and AIV (Ang-(3 -8)), which possess varying remnants of, but significantly non-zero, biological activity by a number of aminopeptidases.…”

Section: Aiimentioning

confidence: 99%

Therapeutic inhibition of the renin angiotensin aldosterone system

Laight¹

2009

Expert Opinion on Therapeutic Patents

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Each intervention has merits and demerits with implications for RAAS 'escape' phenomena, 'dual inhibition' therapy, long-term clinical efficacy and adverse drug reactions. Renin inhibitors offer the most complete RAAS inhibition, but more downstream interventions are likely to recruit supplementary anti-RAAS mediators and receptor signalling pathways. Furthermore, managing hyperkalaemia-stimulated aldosterone escape during combined ACE inhibitor and angiotensin receptor blocker treatment may realise the full clinical potential of dual inhibition therapy.

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“…Wan et al, synthesized the first selective nonpeptide AT 2 R agonist M024/C21 (Fig. 12) by stepwise simplification of the nitrogen containing heterocyclic ring system 41,42 . The substitution of the thienyl-phenyl to the biphenyl scaffold (resembling L162.782, Fig.…”

Section: Fig 11: the Compounds With Dual At 1 R Antagonism And Pparγmentioning

confidence: 99%

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2017

IJPSR

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ABSTRACT:The renin-angiotensin system (RAS) plays an important role in pathogenesis of hypertension, congestive heart failure, and chronic renal failure. In addition to a discussion of the current understanding of the chemical structures and the modes of action of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor (ATR) antagonists, review includes their SAR analysis and chemical modification for improving their activity. Nowadays different modeling strategies are underway to develop tailor made molecules with the best of properties among nonpeptide renin inhibitors, dual action receptor antagonists (e.g. angiotensin and endothelin antagonists, ACE/NEP inhibitors, AT 1 /TxA 2 antagonists, balanced AT 1 /AT 2 antagonists), triple inhibitors. In the first part is given an overview of various ACE inhibitors. The second part is devoted to overview of angiotensin receptor antagonists. The advances that have been made, new opportunities, and future directions of design and development of these classes have been discussed.

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Selective angiotensin II AT2 receptor agonists: Benzamide structure–activity relationships

Cited by 29 publications

References 21 publications

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands

Therapeutic inhibition of the renin angiotensin aldosterone system

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Selective angiotensin II AT2 receptor agonists: Benzamide structure–activity relationships

Cited by 29 publications

References 21 publications

N‐Aryl Isoleucine Derivatives as Angiotensin II AT2 Receptor Ligands

N‐Aryl Isoleucine Derivatives as Angiotensin II AT2 Receptor Ligands

Therapeutic inhibition of the renin angiotensin aldosterone system

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About

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands

N‐Aryl Isoleucine Derivatives as Angiotensin II AT₂ Receptor Ligands