Duncia, John V. published the artcileThe discovery of potent nonpeptide angiotensin II receptor antagonists: a new class of potent antihypertensives, Category: imidazoles-derivatives, the publication is Journal of Medicinal Chemistry (1990), 33(5), 1312-29, database is CAplus and MEDLINE.
A new class of potent antihypertensives, e.g., N-benzylimidazoles, I (R = CH2CO2H, CH2OH, CH2OMe, CH2CO2H, CH2CO2Me; R1 = NO2, NH2, CO2H, CH2CO2H, OMe, etc.) has been discovered that exert their effect through blockade of the angiotensin II (AII) receptor. Most AII antagonists reported so far are peptide mimics of the endogenous vasoconstrictor octapeptide angiotensin II. I are nonpeptides and therefore constitute a new class of potent AII receptor antagonists. Based on the overlap of a conformation of AII with literature lead compound I (R = CH2CO2H R1 = H)(II) a hypothesis was developed suggesting the need for an addnl. acidic functionality to increase the lead’s potency. The substitution of an addnl. carboxylic acid resulted in a 10-fold increase in binding affinity observed for diacid I (R = CH2CO2H, R1 = CO2H). The binding affinities for subsequent compounds were eventually increased 1000-fold over that of II through a systematic SAR study. A structure-affinity relationship showed the presence of four key elements for good activity: an addnl. Ph ring at the N-benzyl para position of the benzylimidazole nucleus, an acidic functionality at the ortho-position of the terminal aromatic ring, a lipophilic side chain at the imidazole 2-position of three to five carbon atoms in length, and a group at the imidazole 5-position capable of hydrogen bonding. The synthesis as well as the pharmacol. activity of the compounds in this new series of AII receptor antagonists are presented.
Journal of Medicinal Chemistry published new progress about 79047-41-9. 79047-41-9 belongs to imidazoles-derivatives, auxiliary class Imidazole,Chloride,Alcohol, name is (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol, and the molecular formula is C8H13ClN2O, Category: imidazoles-derivatives.
Referemce:
https://en.wikipedia.org/wiki/Imidazole,
Imidazole | C3H4N2 – PubChem