Richard M. Keenan

The Development of Potent Angiotensin II Receptor Antagonists Using a Novel Peptide Pharmacophore Model

Richard M. Keenan, Joseph A. Weinstock, Judith C. Hempel, James M. Samanen et autres

The renin-angiotensin system plays a key role in the regulation of blood pressure, fluid and electrolyte balance, and blood volume. In the initial step of the biochemical cascade, the proteolytic enzyme renin catalyzes the breakdown of the high-molecular-weight peptide, angiotensinogen, to angiotensin …

Antagonists of the Calcium Receptor I. Amino Alcohol-Based Parathyroid Hormone Secretagogues

Robert W. Marquis, Amparo M. Lago, James F. Callahan, Robert E. Lee Trout et autres

Functional screening of the former SmithKline Beecham compound collection against the human calcium receptor (CaR) resulted in the identification of the amino alcohol-based hit 2 (IC(50) = 11 microM). Structure-activity studies of 2 focused on the optimization of the right- and left-hand …

us (code pays fourni par la source)

Substituted benzothiadizine inhibitors of Hepatitis C virus polymerase

Antony N. Shaw, Rosanna Tedesco, Ramesh B. Bambal, Deping Chai et autres

us, gb (code pays fourni par la source)

Synthesis and biological activity of heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone derivatives as hepatitis C virus NS5B polymerase inhibitors

Rosanna Tedesco, Deping Chai, Michael G. Darcy, Dashyant Dhanak et autres

us, gb (code pays fourni par la source)

Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase

Dirk A. Heerding, Nelson Rhodes, Jack D. Leber, Tammy J. Clark et autres

Overexpression of AKT has an antiapoptotic effect in many cell types, and expression of dominant negative AKT blocks the ability of a variety of growth factors to promote survival. Therefore, inhibitors of AKT kinase activity might be useful as monotherapy for the …

us (code pays fourni par la source)

Urotensin-II receptor antagonists: Synthesis and SAR of N-cyclic azaalkyl benzamides

Jian Jun Jin, Ming An, Anthony Sapienza, Nambi V. Aiyar et autres

gb, us (code pays fourni par la source)

New benzimidazoles as thrombopoietin receptor agonists

Igor G. Safonov, Dirk A. Heerding, Richard M. Keenan, Alan T. Price et autres

us (code pays fourni par la source)

3-(1,1-Dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, Potent Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase

Rosanna Tedesco, Antony N. Shaw, Ramesh B. Bambal, Deping Chai et autres

Recently, we disclosed a new class of HCV polymerase inhibitors discovered through high-throughput screening (HTS) of the GlaxoSmithKline proprietary compound collection. This interesting class of 3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones potently inhibits HCV polymerase enzymatic activity and inhibits the ability of the subgenomic HCV replicon to …

us (code pays fourni par la source)

Aminoalkoxybenzyl pyrrolidines as novel human urotensin-II receptor antagonists

Jian Jun Jin, Dashyant Dhanak, Steven D. Knight, Katherine L. Widdowson et autres

us (code pays fourni par la source)

In vitro and in vivo biology of a small molecular weight Tpo receptor agonist, SB-497115

Connie L. Erickson‐Miller, Juan I. Luengo, Richard Nicholl, Daphne Williams et autres

2565 SB-497115 is an orally bioavailable, non-peptidyl, small molecule thrombopoietin receptor (TpoR) agonist under development for treatment of thrombocytopenia. SB-497115 requires TpoR to activate the JAK/STAT signalling pathway and stimulates transcription through STAT based and megakaryocyte specific (gpIIb) promoters. SB-497115 did not …

gb (code pays fourni par la source)

Nonpeptidic urotensin‐II receptor antagonists I: in vitro pharmacological characterization of SB‐706375

Stephen A. Douglas, David J. Behm, Nambi V. Aiyar, Diane P. Naselsky et autres

1. SB-706375 potently inhibited [(125)I]hU-II binding to both mammalian recombinant and 'native' UT receptors (K(i) 4.7+/-1.5 to 20.7+/-3.6 nM at rodent, feline and primate recombinant UT receptors and K(i) 5.4+/-0.4 nM at the endogenous UT receptor in SJRH30 cells). 2. Prior exposure …

gb, us (code pays fourni par la source)

Identification of small molecule inhibitors of the hepatitis C virus RNA-dependent RNA polymerase from a pyrrolidine combinatorial mixture

George Burton, Thomas W. Ku, Thomas J. Carr, Terry J. Kiesow et autres

us, gb (code pays fourni par la source)