Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a dihydroxyethylene transition-state mimic at the scissile bond to impart greater inhibitory potency

1988 ◽  
Vol 31 (12) ◽  
pp. 2264-2276 ◽  
Author(s):  
Jay R. Luly ◽  
Nwe BaMaung ◽  
Jeff Soderquist ◽  
Anthony K. L. Fung ◽  
Herman Stein ◽  
...  
Keyword(s):  
Transition State ◽  
Inhibitory Potency ◽  
Renin Inhibitors ◽  
Scissile Bond

Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bond

1989 ◽  
Vol 32 (7) ◽  
pp. 1652-1661 ◽  
Author(s):  
Mark C. Allen ◽  
Walter Fuhrer ◽  
Brian Tuck ◽  
Roy Wade ◽  
Jeanette M. Wood
Keyword(s):  
Transition State ◽  
Phosphorus Acid ◽  
Transition State Analog ◽  
Renin Inhibitors ◽  
Scissile Bond

Renin inhibitors. Dipeptide analogs of angiotensinogen incorporating transition-state, nonpeptidic replacements at the scissile bond

1987 ◽  
Vol 30 (10) ◽  
pp. 1729-1737 ◽  
Author(s):  
Giorgio Bolis ◽  
Anthony K. L. Fung ◽  
Jonathan Greer ◽  
Hollis D. Kleinert ◽  
Patrick A. Marcotte ◽  
...  
Keyword(s):  
Transition State ◽  
Renin Inhibitors ◽  
Scissile Bond

scholarly journals Polyvalent transition-state analogues of sialyl substrates strongly inhibit bacterial sialidases.

2020 ◽  
Author(s):  
coralie assailly ◽  
clarisse bridot ◽  
amélie saumonneau ◽  
paul lottin ◽  
Benoit Roubinet ◽  
...  
Keyword(s):  
Transition State ◽  
Important Class ◽  
Inhibitory Potency ◽  
Polymeric Scaffolds ◽  
Transition State Analogues

<div>Conjugation of the transitionstate-cation analogue DANA to polymeric scaffolds led to highly potent inhibitors of bacterial sialidases. Each clustered DANA on the polymers saw its inhibitory potency for S. pneumoniae or B. thetaiotaomicron sialidases improved by more than four orders of magnitude. This extends the multivalent concept to this important class of enzymes.</div><div><br></div>

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

Renin inhibitors based on novel dipeptide analogs. Incorporation of the dehydrohydroxyethylene isostere at the scissile bond

1987 ◽  
Vol 30 (11) ◽  
pp. 1978-1983 ◽  
Author(s):  
Dale J. Kempf ◽  
Ed De Lara ◽  
Herman H. Stein ◽  
Jerome Cohen ◽  
Jacob J. Plattner
Keyword(s):  
Renin Inhibitors ◽  
Scissile Bond

Renin inhibitors. Free-Wilson and correlation analysis of the inhibitory potency of a series of pepstatin analogs on plasma renin

1987 ◽  
Vol 30 (12) ◽  
pp. 2287-2291 ◽  
Author(s):  
Dino Nisato ◽  
Jean Wagnon ◽  
Georges Callet ◽  
Daniel Mettefeu ◽  
Jean Louis Assens ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Plasma Renin ◽  
Inhibitory Potency ◽  
Renin Inhibitors

Synthesis and Anti-HIV Activity of Prodrugs Derived from Saquinavir and Indinavir

2000 ◽  
Vol 11 (2) ◽  
pp. 97-110 ◽  
Author(s):  
Audrey Farèse-Di Giorgio ◽  
Marielle Rouquayrol ◽  
Jacques Greiner ◽  
Anne-Marie Aubertin ◽  
Pierre Vierling ◽  
...  
Keyword(s):  
Transition State ◽  
Therapeutic Potential ◽  
Parent Drug ◽  
Inhibitory Potency ◽  
Respective Parent ◽  
Hiv Inhibition ◽  
Hydrolysis Of ◽  
Anti Hiv ◽  
In Vitro Stability

With a view to improving the pharmacological properties, safety and pharmacokinetic profiles of current protease inhibitors, the synthesis of various acyl-substituted saquinavir and indinavir prodrugs, their in vitro stability with respect to hydrolysis and their anti-HIV (LAI and HTLV IIIB) activity and cytotoxicity in CEM-SS and MT4 cells have been investigated. Hydrolysis of the ester bond and liberation of the active free drug was found to be crucial for HIV inhibition: the faster the hydrolysis, the closer the anti-HIV activity was to that of the respective parent drug. This is the case for most of the C-14-substituted indinavir and saquinavir derivatives (IC50 from 10 to 360 nM for ester half-lives of 90 min to 40 h). Concomitantly, the level of HIV inhibition is very low for the prodrugs for which hydrolysis is very slow. This is the case with the myristoyl or oleyl saquinavir esters, owing to the stable masking of the hydroxyl that is part of the peptidomimetic non-cleavable transition state isostere responsible for the inhibitory potency of saquinavir (and indinavir). In contrast, the anti-HIV activity of the monosubstituted C-8 indinavir prodrugs seems not to be correlated with their resistance to hydrolysis, as expected (the C-8 hydroxyl of indinavir is not involved in the transition state isostere). No cytotoxicity was detected for the indinavir and saquinavir prodrugs for concentrations as high as 10 or even 100 μM, thus indicating promising therapeutic potential.

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