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Taylor

Bio: Taylor is an academic researcher from Pfizer. The author has contributed to research in topics: Bioavailability & Renin–angiotensin system. The author has an hindex of 2, co-authored 2 publications receiving 340 citations.

Papers
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Journal ArticleDOI
TL;DR: A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position that exhibited oral blood pressure lowering activity in high-renin normotensive monkeys and was selected for further evaluation in renal hypertensive monkeys on the basis of its superior efficacy and duration of action.
Abstract: A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.

343 citations

Journal ArticleDOI
TL;DR: While uptake into hepatic cells was rapid regardless of partition coefficient or molecular weight, rate of appearance in bile was dependent on the molecular weight of the compounds, and compounds with higher lipophilicity were better absorbed from the intestine.
Abstract: A series of radiolabeled compounds related to renin inhibitor structures was synthesized to represent a range of physicochemical properties. These compounds were tested in assays for intestinal absorption and hepatic clearance in order to define parameters conducive to optimizing bioavailability. In general, compounds with higher lipophilicity were better absorbed from the intestine. Absorption may also be dependent on molecular charge, as compounds with ionizable functionality were less well-absorbed than neutral compounds. Neutral compounds showed some dependency on molecular weight, with smaller compounds exhibiting better absorption. While uptake into hepatic cells was rapid regardless of partition coefficient or molecular weight, rate of appearance in bile was dependent on the molecular weight of the compounds.

27 citations


Cited by
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Journal ArticleDOI
TL;DR: Various named reactions, multi-component reactions and the synthesis of heterocyclic compounds are discussed including the use of various energy input systems such as microwave- and ultrasound irradiation, among others.
Abstract: Catalyst-free reactions developed during the last decade and the latest developments in this emerging field are summarized with a focus on catalyst-free reactions in-water and on-water. Various named reactions, multi-component reactions and the synthesis of heterocyclic compounds are discussed including the use of various energy input systems such as microwave- and ultrasound irradiation, among others. Organic chemists and the practitioners of this art both in academia and industry hopefully will continue to design benign methodologies for organic synthesis in aqueous media under catalyst-free conditions by using alternative energy inputs based on fundamental principles.

533 citations

Journal ArticleDOI
TL;DR: Thiazole 3 and pyrazolo[1,5-a]pyrimidine 21 b were found to exhibit the most potent in vitro antifungal activity with MICs against A. fumigatus and F. oxysporum.

323 citations

Journal ArticleDOI
TL;DR: A nonlinear computational neural network model developed by using the genetic algorithm with a neural network fitness evaluator to estimate percent human intestinal absorption (%HIA) is an attractive alternative to experimental measurements.
Abstract: Prediction of human intestinal absorption (HIA) is a major goal in the development of oral drugs. The application of combinatorial chemistry methods to drug discovery has dramatically increased the demand for rapid and efficient models for estimating HIA and other biopharmaceutical properties. While experimental methods for measurement of intestinal absorption have been developed and are used widely, computational approaches provide an attractive alternative.

317 citations

Journal ArticleDOI
TL;DR: Among the tested compounds, the most effective compounds with MIC value in the range of 6.25-25 microg/ml are 4a, 4n, 4z, 5a, 5b, 6a and 6b against three fungal strains viz.

310 citations

Journal ArticleDOI
TL;DR: In this article, the use of environmentally benign and inexpensive eutectic solvents (DESs) as solvent and catalyst in the field of organic chemistry is discussed and compared.

295 citations