Selenosartans: Novel selenophene analogues of milfasartan and eprosartan

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 3; pp. 1241 - 1244
• Main Authors: Grange, Rebecca L., Ziogas, James, North, Andrea J., Angus, James A., Schiesser, Carl H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.02.2008; Elsevier
• Subjects: Acrylates - chemical synthesis; Acrylates - chemistry; Acrylates - pharmacology; Angiotensin II Type 1 Receptor Blockers - chemical synthesis; Angiotensin II Type 1 Receptor Blockers - chemistry; Angiotensin II Type 1 Receptor Blockers - pharmacokinetics; Animals; Antihypertensive Agents - chemical synthesis; Antihypertensive Agents - chemistry; Antihypertensive Agents - pharmacology; AT 1 receptor antagonist sartan; Biological and medical sciences; Cricetinae; Female; Imidazoles - chemical synthesis; Imidazoles - chemistry; Imidazoles - pharmacology; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Organoselenium Compounds - chemical synthesis; Organoselenium Compounds - chemistry; Organoselenium Compounds - pharmacokinetics; Ovary - cytology; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptor, Angiotensin, Type 1 - metabolism; Stereoisomerism; Structure-Activity Relationship; Sulfur - chemistry; Sulfur - pharmacokinetics; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacokinetics; Thiophenes - pharmacology; AT 1 receptor antagonist sartan; Tetrazole derivatives; Rodentia; AT1 angiotensin receptor; In vitro; Biological activity; CHO cell line; Milfasartan; Ovary; Vertebrata; Mammalia; Cell line; Biphenyl derivatives; Pyrimidine derivatives; Eprosartan; Angiotensin antagonist; AT1 receptor antagonist sartan; Angiotensin II; Chemical synthesis; Hamster
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2007.11.136

The synthesis and preliminary evaluation of selenophene-containing sartans (e.g. 4; pK B = 8.3) is reported. A series of selenophene analogues of the thiophene-containing antihypertensives milfasartan and eprosartan were prepared and tested for AT 1 receptor antagonist properties. All four selenophene compounds proved to be potent AT 1 receptor antagonists, with pK B estimates indicating that these selenides are at least as effective as the thiophene parent compounds at blocking AT 1 receptor mediated responses. These results reveal that replacement of sulfur with selenium in thiophene-containing sartans does not interfere with sartan activity.