The discovery of DuP 753, a potent, orally active nonpeptide angiotensin II receptor antagonist

JV Duncia, DJ Carini, AT Chiu… - Medicinal research …, 1992 - Wiley Online Library
One of the most important regulators of blood pressure is the renin-angiotensin system (RAS)(Fig.
l).* The enzyme renin, manufactured in the kidney, cleaves circulating …

Identification of angiotensin II receptor subtypes

…, WF Herblin, DE McCall, RJ Ardecky, DJ Carini… - Biochemical and …, 1989 - Elsevier
We have demonstrated the existence of two distinct subtypes of the angiotensin II receptor
in the rat adrenal gland using radioligand binding and tissue section autoradiography. The …

Nonpeptide angiotensin II receptor antagonists: the discovery of a series of N-(biphenylylmethyl) imidazoles as potent, orally active antihypertensives

DJ Carini, JV Duncia, PE Aldrich, AT Chiu… - Journal of medicinal …, 1991 - ACS Publications
… The ether 5, the carbamates (eg 51), the ureas (eg 55), and the amide 58 were prepared
by utilizing chemistry previously described by Duncia et al.38 and Carini et al.3b In the key …

Comparative QSAR: angiotensin II antagonists

A Kurup, R Garg, DJ Carini, C Hansch - Chemical Reviews, 2001 - ACS Publications
The use of quantitative structure-activity relationships (QSAR) since their advent in 19621
has become increasingly helpful in understanding many aspects of chemical-biological …

The discovery of potent nonpeptide angiotensin II receptor antagonists: a new class of potent antihypertensives

JV Duncia, AT Chiu, DJ Carini… - Journal of medicinal …, 1990 - ACS Publications
A new class of potent antihypertensives has been discovered that exert their effect through
blockade of the angiotensin II (All) receptor. Most AH antagonists reported so far are peptide …

Discovery of losartan, the first angiotensin II receptor antagonist.

PB Timmermans, JV Duncia, DJ Carini… - Journal of human …, 1995 - europepmc.org
The'discovery'of losartan represents three separate discoveries:(1) losartan as the unique
biphenyltetrazole molecule and the first of a new chemical class;(2) losartan as a tool to …

Nonpeptide angiotensin II receptor antagonists. XI. Pharmacology of EXP3174: an active metabolite of DuP 753, an orally active antihypertensive agent.

…, WA Price, AT Chiu, JV Duncia, DJ Carini… - … of Pharmacology and …, 1990 - ASPET
This report describes the pharmacology of (2-n-butyl-4-chloro-1- [(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic
acid (EXP3174). EXP3174 is a major metabolite …

Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent.

…, DE McCall, WA Price, PC Wong, DJ Carini… - … of Pharmacology and …, 1990 - ASPET
2-n-Butyl-4-chloro-5-hydroxymethyl-1-[2'-(1H-tetrazole-5-yl)biphenyl-4-yl) methyl]imidazole,
potassium salt (DuP 753) is a potent, po active antihypertensive agent exerting its action by …

(Trimethylsilyl) cyclopentene annulation: a regiocontrolled approach to the synthesis of five-membered rings

RL Danheiser, DJ Carini, A Basak - Journal of the American …, 1981 - ACS Publications
0 Annulations were carried out with the use of 1.0-1.5 equiv of aliene and 1.5 equiv of TiCl „in
CH2C12 at-78 C for 1 h (-20 C, 2 h for entry 4). Reactions were quenched by rapid …

[PDF][PDF] Nonpeptide angiotensin II receptor antagonists. VIII. Characterization of functional antagonism displayed by DuP 753, an orally active antihypertensive agent.

…, WA Price, AT Chiu, JV Duncia, DJ Carini… - … of Pharmacology and …, 1990 - Citeseer
In the spinal pithed rat, DuP 753, 2-n-butyl-4-chloro-5-hydroxy methyl-i-[(2'-(i H-tetrazol-5-yI)
biphenyl4-yl) methyl] imidazole potassium salt, inhibited competitively the pressor response …