Quinazolinone Biphenyl Acylsulfonamides: A potent new class of angiotensin-II receptor antagonists

Chakravarty, Prasun K.; Strelitz, R. A.; Chen, Tsing-Bau; Chang, Raymond S.L.; Lotti, Victor J.; Zingaro, Gloria J.; Schorn, Terry W.; Kivlighn, Salah D.; Siegel, Peter K.S.; Patchett, Arthur A.; Greenlee, William J.

doi:10.1016/s0960-894x(01)81125-2

Cited by 16 publications

(3 citation statements)

References 9 publications

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“…The enhanced AT 2 affinity observed for antagonists such as MK-996 (AT 1 IC 50 = 0.2 nM; AT 2 IC 50 = 2.9 μM) 129 and L-159,913 (AT 1 IC 50 = 0.5 nM; AT 2 IC 50 = 450 nM) 226 relative to their tetrazole analogs demonstrated that acylsulfonamide groups can enhance AT 2 affinity. That this effect is general is illustrated by the near-balanced activity of the imidazopyridine L-159,894 (AT 1 IC 50 = 0.05 nM; AT 2 IC 50 = 18 nM), the quinazolinone L-159,958 (AT 1 IC 50 = 3 nM; AT 2 IC 50 = 80 nM), and the triazolinone L-162,234 (AT 1 IC 50 = 0.45 nM; AT 2 IC 50 = 17 nM), which were derived from AT 1 -selective heterocyclic biphenyltetrazole antagonist series. The imidazole 6 (AT 1 IC 50 = 1.9 nM; AT 2 IC 50 = 500 nM) and the related sulfonylurea analog S0029 (AT 1 IC 50 = 0.3 nM; AT 2 IC 50 = 775 nM) provide additional examples.…”

Section: Balanced Angiotensin II Antagonistsmentioning

confidence: 98%

Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy

et al. 1996

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Section: Balanced Angiotensin II Antagonistsmentioning

confidence: 98%

Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy

et al. 1996

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“…Substituted quinazolone groups were previously successfully employed in programs aimed at making selective AT2R antagonists. [121][122][123][124][125][126][127] As a consequence of these findings, substituted quinazolinone groups were attached to the biaryl scaffold of 10 to replace the bicyclic imidazopyridine ring system, as exemplified by the most potent and AT2R…”

Section: (I) From the Methylene Imidazopyridine To Quinazolinonesmentioning

confidence: 99%

Small‐molecule AT2 receptor agonists

Hallberg

Sumners

Steckelings

et al. 2017

Medicinal Research Reviews

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The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist with the highest affinity for the AT2R reported to date (K = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.

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“…Benzimidazoles were found to possess number of pharmacological, biological, and microbiological (Chakravarty et al, 1994) activities, which includes antimicrobial (Rathee et al, 2011), antitubercular activity. Benzimidazoles were also used as antitumor/ anticancer/antihypertensive agent (Kumar et al, 2002) against lung cancer human cells (A549) and breast cancer human cells (MCF 7).…”

Section: Introductionmentioning

confidence: 99%

Multistep synthesis of 1-[{(5-alkenyl/hydroxyalkenylsubstituted)-1,3,4-oxadiazol-2-yl}-methyl]-2-methyl-1H-benzimidazole series and in vitro anticancer screening, SAR studies

et al. 2014

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A novel series of hydroxy and non-hydroxy long chain substituted 1,3,4-oxadiazole moiety bearing 2-methyl-1H-benzimidazoles 15(a-d) have been synthesized from cyclization reaction of 2-(2-methyl-1H-benzimidazol-1-yl) acetohydrazide (13) with different unsaturated hydroxy and non-hydroxy fatty esters in the presence of phosphorus oxychloride and product obtained in appreciable yield. Compound (13) was synthesized from the corresponding ethyl (2-methyl-1H-benzimidazol-1-yl) acetate (12) and 2-methyl-1H-benzimidazole (11). All the synthesized compounds were characterized with the help of IR, 1 H NMR, 13 C NMR, and mass spectral studies. These compounds were tested for cytotoxic (or antiproliferative) activity against normal human blood cells (PBMCs), Hep3B (human hepatocellular carcinoma), MCF 7 (human breast adenocarcinoma), and HeLa (human cervical carcinoma) cell lines.

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Quinazolinone Biphenyl Acylsulfonamides: A potent new class of angiotensin-II receptor antagonists

Cited by 16 publications

References 9 publications

Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy

Nonpeptide Angiotensin II Receptor Antagonists: The Next Generation in Antihypertensive Therapy

Small‐molecule AT2 receptor agonists

Multistep synthesis of 1-[{(5-alkenyl/hydroxyalkenylsubstituted)-1,3,4-oxadiazol-2-yl}-methyl]-2-methyl-1H-benzimidazole series and in vitro anticancer screening, SAR studies

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