Letters in Drug Design & Discovery

ISSN: 1570-1808

Letters in Drug Design & Discovery
Volume 2, Number 8, December 2005

Rational Design of the New Antihypertensive I1-Receptor Ligand 2-(2-Biphenyl 2-yl-1-methyl-ethyl)-4,5-dihydro-1H-imidazole

F. Gentili, P. Bousquet, A. Carrieri, J. Feldman, F. Ghelfi, M. Giannella, A. Piergentili, W. Quaglia, C. Vesprini & M. Pigini Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, via S. Agostino 1, 62032 Camerino, Italy The new antihypertensive I1-receptor ligand [title compound, (4)] has been prepared by rational modification of the corresponding antagonist (3). Cardiovascular effects are produced eclusively by (S)-(+)-enantiomer..

[Back to top] [Purchase Issue/Articles]

Docking Study, Synthesis and SAH-Hydrolase Inhibitory Activity of L-Adeninylalanine and Related Analogues

Nicolas Floquet, Samuel Leroy, Murielle Muzard, Georges Guillerm & Jean-Bernard Behr Laboratoire Réactions Sélectives et Applications UMR 6519, UFR Sciences - CNRS, BP 1039, 51687 Reims Cedex 2, France

[Back to top] [Purchase Issue/Articles]

Anti-tumour Activity of Some Polydentate N-Ligands: N,N-bis-(3-Substituted-5-Methylpyrazol-1yl Methyl) Arylamines and N,N,N’,N’-Tetra-[(3-Substituted-5-Methylpyrazol-1yl] Para-Phenylenediamines

T. Ben Hadda, A.T. Kotchevar, M. Daoudi, B. Bennani, N. Ben Larbi & A. Kerbal Laboratoire d’Activation Moléculaire, Département de Chimie, Faculté des Sciences, 60000 Oujda, Maroc Five polydentate ligands 2-6 were prepared from arylamines and p-phenylenediamine with precursors 1a-b. The polydentate (2-4) and (5) showed marked activity against cancer cell lines. The substituents (R and R’) appear to play a key role in the cytotoxic potency of this class of compounds.

[Back to top] [Purchase Issue/Articles]

[Back to top] [Purchase Issue/Articles]

Identification of Privileged Scaffolds from a Diversified Chemical Library for β-Secretase Inhibition

Nicolas Pietrancosta, Gilles Quéléver, Cédrik Garino, Younes Laras, Stéphane Burlet & Jean-Louis Kraus Laboratoire de Chimie Biomoléculaire, INSERM U-623, Institut de Biologie du Développement de Marseille (CNRS - INSERM - Université de la Méditerranée), Faculté des Sciences de Luminy, case 907, 13288 Marseille Cedex 09, France Hexahydrobenzothiazole was identified in our 1,300-member academic library through rational selection prior to enzymatic screening on BACE-1 assay. The identified privileged scaffold has been optimised and a preliminary structure-activity study has been performed.

[Back to top] [Purchase Issue/Articles]

Synthesis and Biological Evaluation of 1,2,4-Triazolo[2,3-a] pyrrole Derivatives as Alpha-4 (α4) Integrin Antagonists

Edward C. Lawson, William A. Kinney, Rosemary J. Santulli, Carol M. Fisher, Bruce P. Damiano & Bruce E. Maryanoff Vascular Research Team, Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477-0776, USA A novel series of a4 integrin antagonists is reported possessing a 1,2,4-triazolo[2,3-a]pyrrole structural subunit (viz. 1). Compound 11 inhibited a4b1–VCAM-1 and a4b7–MAdCAM-1 adhesion with IC50 values of 80 and 20 nM, respectively.

[Back to top] [Purchase Issue/Articles]

[Back to top] [Purchase Issue/Articles]

Initial Structure-Activity Relationships for a Caprolactam-based Series of Neutral Factor Xa Inhibitors: Lead Identification

Gregory S. Bisacchi, Philip D. Stein, Jack Z. Gougoutas, Karen S. Hartl, R. Michael Lawrence, Eddie Liu, Andrew Pudzianowski, William A. Schumacher, Doree Sitkoff, Thomas E. Steinbacher, James Sutton, Zhaoxiao Zhang & Steven M. Seiler AstraZeneca, 35 Gatehouse Dr. Waltham, MA, 02451, USA A lead series of neutral caprolactam-based Factor Xa inhibitors is described. 8c is 145-fold more potent than 1, and demonstrates efficacy in a rat model of venous thrombosis.

[Back to top] [Purchase Issue/Articles]

Synthesis and Evaluation of p-Nitrophenyl β-D-Glucopyranosiduronic Analogues as New Triggers for β-Glucuronidase Mediated Prodrug Mono-Therapy

Damien Combaud, Mickaël Thomas, Sébastien Papot & Jean-Pierre Gesson UMR 6514: Synthèse et Réactivité des Substances Naturelles, Université de Poitiers et CNRS, 40, Av. du Recteur Pineau, F-86022 Poitiers, France Four new p-nitrophenyl b-D-glucuronide analogues have been prepared and evaluated as new triggers for b-glucuronidase mediated P.M.T. (Prodrug Mono-Therapy).

[Back to top] [Purchase Issue/Articles]

[Back to top] [Purchase Issue/Articles]