Chang, Linda L. published the artcilePotent and orally active angiotensin II receptor antagonists with equal affinity for human AT1 and AT2 subtypes, Application In Synthesis of 76283-09-5, the publication is Journal of Medicinal Chemistry (1995), 38(19), 3741-58, database is CAplus and MEDLINE.
In order to block the effects induced by the interactions between angiotensin II (AII) and both AT1 and AT2 receptors, the authors have pursued the discovery of orally active non-peptide AII antagonists that exhibit potent and equal affinity for human AT1 and AT2 receptor subtypes. A series of previously prepared nanomolar (IC50) trisubstituted 1,2,4-triazolinone biphenylsulfonamide dual-acting AII antagonists has been modified at five different positions in order to increase AT2 binding affinity, maintain AT1 activity, and reduce the human adrenal AT2/AT1 potency ratio (IC50 ratio) from ≥10. The targeted human adrenal potency ratio of ≤1 was achieved with a number of compounds possessing an Et group at C5 of the triazolinone and a 3-fluoro substituent at the N4-biarylmethyl moiety. The most favored of these was triazolinone I which exhibited subnanomolar potency at both the AT1 (rabbit aorta) and AT2 (rat midbrain) receptors, with a slight preference for the latter, and had a human adrenal AT2/AT1 IC50 ratio of 1. This tert-Bu sulfonylcarbamate had excellent i.v. activity at 1 mg/kg (100% peak inhibition, ≥4 h duration of action) and is orally active at 3 mg/kg with >6 h duration of action in a conscious rat model. The present study shows that the NH of the amide on the N2-aryl moiety is not required for subnanomolar binding affinity to either receptor subtype, although a keto functionality at this position is essential for acceptable AT2 binding. Receptor-ligand binding interactions derived from the structure-activity relationships are discussed with respect to both receptor subtypes.
Journal of Medicinal Chemistry published new progress about 76283-09-5. 76283-09-5 belongs to bromides-buliding-blocks, auxiliary class Fluoride,Bromide,Benzyl bromide,Benzene, name is 4-Bromo-1-(bromomethyl)-2-fluorobenzene, and the molecular formula is C7H5Br2F, Application In Synthesis of 76283-09-5.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary