EXP597, a nonpeptide angiotensin II receptor antagonist with high affinities for the angiotensin AT1 and AT2 receptor subtypes.
AT1 and AT2 are the two major receptor subtypes for angiotensin II that have been pharmacologically defined by using the selective ligands losartan and PD123177, respectively. EXP597 (4-[(5-(2-benzoyl)benzyloxycarbonyl-4-ethyl-2-n-propylimidazole-1- yl)methyl]-3-fluoro-2'-isoamyloxycarbonylaminosulfonyl-[1,1']-biph enyl, potassium salt) is a nonpeptide angiotensin II receptor ligand which in the rat adrenal exhibits binding affinities (IC50) of 0.5 and 0.7 nM for angiotensin AT1 and AT2 receptor subtypes, respectively. Further, EXP597 is an insurmountable angiotensin II receptor antagonist in the isolated rabbit aorta and lowers blood pressure in renal hypertensive rats with i.v. and p.o. ED30 values of 0.05 and 0.9 mg/kg, respectively.
Wong
P C
PC
Cardiovascular Diseases Research, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.
Duncia
J V
JV
Santella
J B
JB
Smith
R D
RD
Wexler
R R
RR
Timmermans
P B
PB
Chiu
A T
AT
D000284:Administration, Oral; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006977:Hypertension, Renal / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013449:Sulfonamides; D013777:Tetrazoles; C066253:PD 123177; C090811:EXP 597; D019808:Losartan