Approaches to human renin inhibitors with improved bioavailability

Peptides ◽  
1990 ◽  
pp. 411-412 ◽  
Author(s):  
William J. Greenlee ◽  
Jan tenBroeke ◽  
Stephen E. de Laszlo ◽  
Prasun K. Chakravarty ◽  
Valerie J. Camara ◽  
...  
Keyword(s):  
Renin Inhibitors ◽  
Human Renin

scholarly journals Synthesis and structure-activity relationships of human renin inhibitors designed from angiotensinogen transition state.

1990 ◽  
Vol 38 (9) ◽  
pp. 2487-2493 ◽  
Author(s):  
Kinji IIZUKA ◽  
Tetsuhide KAMIJO ◽  
Hiromu HARADA ◽  
Kenji AKAHANE ◽  
Tetsuhiro KUBOTA ◽  
...  
Keyword(s):  
Transition State ◽  
Renin Inhibitors ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Human Renin

New human renin inhibitors containing an unnatural amino acid, norstatine

1988 ◽  
Vol 31 (4) ◽  
pp. 701-704 ◽  
Author(s):  
Kinji Iizuka ◽  
Tetsuhide Kamijo ◽  
Tetsuhiro Kubota ◽  
Kenji Akahane ◽  
Hideaki Umeyama ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unnatural Amino Acid ◽  
Renin Inhibitors ◽  
Human Renin

Highly potent, orally active diester macrocyclic human renin inhibitors

1992 ◽  
Vol 35 (21) ◽  
pp. 3755-3773 ◽  
Author(s):  
Ann E. Weber ◽  
Mark G. Steiner ◽  
Philip A. Krieter ◽  
Adria E. Colletti ◽  
James R. Tata ◽  
...  
Keyword(s):  
Renin Inhibitors ◽  
Human Renin ◽  
Orally Active

The human renin infused rat: use as an in vivo model for the biological evaluation of human renin inhibitors

1999 ◽  
Vol 77 (11) ◽  
pp. 886-895 ◽  
Author(s):  
Gordon Bolger ◽  
Jean-Claude Vigeant ◽  
Francine Liard ◽  
Bruno Simoneau ◽  
Diane Thibeault ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pressor Response ◽  
Biological Evaluation ◽  
In Vivo Model ◽  
Dependent Manner ◽  
Renin Inhibitors ◽  
Human Renin ◽  
Dose Dependent

The human renin infused rat model (HRIRM) was used as an in vivo small-animal model for evaluating the efficacy of a collection of inhibitors of human renin. The intravenous infusion of recombinant human renin (2.4 µg·kg-1·min-1) in the ganglion-blocked, nephrectomized rat produced a mean blood pressor response of 47 ± 3 mmHg (1 mmHg = 133.3 Pa), which was reduced by captopril, enalkiren, and losartan in a dose-dependent manner following oral administration, with ED50 values of 0.3 ± 0.1, 2.5 ± 0.9, and 5.2 ± 1.6 mg/kg, respectively. A series of peptidomimetic P2-P3 butanediamide renin inhibitors inhibited purified recombinant human renin in vitro in a concentration-dependent manner, with IC50 values ranging from 0.4 to 20 nM at pH 6.0, with a higher range of IC50 values (0.8-80 nM) observed at pH 7.4. Following i.v. administration of renin inhibitors, the pressor response to infused human renin in the HRIRM was inhibited in a dose-dependent manner, with ED50 values ranging from 4 to 600 µg/kg. The in vivo inhibition of human renin following i.v. administration in the rat correlated significantly better with the in vitro inhibition of human renin at pH 7.4 (r = 0.8) compared with pH 6.0 (r = 0.5). Oral administration of renin inhibitors also resulted in a dose-dependent inhibition of the pressor response to infused human renin, with ED50 values ranging from 0.4 to 6.0 mg/kg and the identification of six renin inhibitors with an oral potency of <1 mg/kg. The ED50 of renin inhibitors for inhibition of angiotensin I formation in vivo was highly correlated (r = 0.9) with the ED50 for inhibition of the pressor response. These results demonstrate the high potency, dose dependence, and availability following oral administration of the butanediamide series of renin inhibitors.Key words: renin-angiotensin system, recombinant human renin, rat, renin inhibitors.

scholarly journals New fluoroketones as human renin inhibitors

FEBS Letters ◽  
1989 ◽  
Vol 249 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Céline Tarnus ◽  
Michel J. Jung ◽  
Jean-Marc Rémy ◽  
Sylvie Baltzer ◽  
Daniel G. Schirlin
Keyword(s):  
Renin Inhibitors ◽  
Human Renin

Tripeptide aminoalcohols: A new class of human renin inhibitors

Peptides ◽  
1988 ◽  
pp. 131-133
Author(s):  
Sesha Natarajan ◽  
Charles A. Free ◽  
Emily F. Sabo ◽  
James Lin ◽  
Ervin R. Spitzmiller ◽  
...  
Keyword(s):  
Renin Inhibitors ◽  
New Class ◽  
Human Renin

New classes of potent and bioavailable human renin inhibitors

2009 ◽  
Vol 19 (23) ◽  
pp. 6762-6765 ◽  
Author(s):  
L’uboš Remeň ◽  
Olivier Bezençon ◽  
Sylvia Richard-Bildstein ◽  
Daniel Bur ◽  
Lars Prade ◽  
...  
Keyword(s):  
Renin Inhibitors ◽  
Human Renin

scholarly journals Characterization of a stable, hypertensive rat model suitable for the consecutive evaluation of human renin inhibitors

2011 ◽  
Vol 12 (3) ◽  
pp. 133-145 ◽  
Author(s):  
René St-Jacques ◽  
Sylvie Toulmond ◽  
Anick Auger ◽  
Christoph Binkert ◽  
Wanda Cromlish ◽  
...  
Keyword(s):  
Rat Model ◽  
Renin Inhibitors ◽  
Hypertensive Rat ◽  
Human Renin

Identification of novel human renin inhibitors through a combined approach of pharmacophore modelling, molecular DFT analysis and in silico screening

2017 ◽  
Vol 69 ◽  
pp. 28-40 ◽  
Author(s):  
Dhrubajyoti Gogoi ◽  
Vishwa Jyoti Baruah ◽  
Amrita Kashyap Chaliha ◽  
Bibhuti Bhushan Kakoti ◽  
Diganta Sarma ◽  
...  
Keyword(s):  
In Silico ◽  
Combined Approach ◽  
In Silico Screening ◽  
Pharmacophore Modelling ◽  
Renin Inhibitors ◽  
Human Renin

scholarly journals Development, evaluation and application of 3D QSAR Pharmacophore model in the discovery of potential human renin inhibitors

2011 ◽  
Vol 12 (Suppl 14) ◽  
pp. S4 ◽  
Author(s):  
Shalini John ◽  
Sundarapandian Thangapandian ◽  
Mahreen Arooj ◽  
Jong Hong ◽  
Kwang Kim ◽  
...  
Keyword(s):  
Pharmacophore Model ◽  
3D Qsar ◽  
Renin Inhibitors ◽  
Human Renin ◽  
Development Evaluation
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