Table of Contents
May 6, 2004
Volume 47, Issue 10
Pages 2393-2716
About the Cover: Molecular modeling of overlayed trisubstituted acridine derivatives (mauve and green) complexed with G-quadruplex DNA (Harrison, R. J.; et al. J. Med. Chem. 2003, 46, 4463-4476).
Perspective
Lessons Learned from Marketed and Investigational Prodrugs
Peter Ettmayer, Gordon L. Amidon, Bernd Clement, and Bernard Testa
pp 2393–2404Publication Date (Web): April 13, 2004 (Perspective)
DOI: 10.1021/jm0303812
Hi-Res PDF Letters
Piperazine-Based CCR5 Antagonists as HIV-1 Inhibitors. IV. Discovery of 1-[(4,6-Dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-{2-methoxy-1(R)-4-(trifluoromethyl)phenyl}ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a Potent, Highly Selective, and Orally Bioavailable CCR5 Antagonist
Jayaram R. Tagat, Stuart W. McCombie, Dennis Nazareno, Marc A. Labroli, Yushi Xiao, Ruo W. Steensma, Julie M. Strizki, Bahige M. Baroudy, Kathleen Cox, Jean Lachowicz, Geoffrey Varty, and Robert Watkins
pp 2405–2408Publication Date (Web): April 09, 2004 (Letter)
DOI: 10.1021/jm0304515
Synthesis and Evaluation of Oxazaborolidines for Antibacterial Activity against Streptococcus mutans
Adel Jabbour, Doron Steinberg, Valery M. Dembitsky, Arieh Moussaieff, Batia Zaks, and Morris Srebnik
pp 2409–2410Publication Date (Web): April 07, 2004 (Letter)
DOI: 10.1021/jm049899b
Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator
J. Joossens, P. Van der Veken, A.-M. Lambeir, K. Augustyns, and A. Haemers
pp 2411–2413Publication Date (Web): April 06, 2004 (Letter)
DOI: 10.1021/jm0499209
Identification of 4-(1H-Imidazol-4(5)-ylmethyl)pyridine (Immethridine) as a Novel, Potent, and Highly Selective Histamine H3 Receptor Agonist
Ruengwit Kitbunnadaj, Obbe P. Zuiderveld, Bernard Christophe, Saskia Hulscher, Wiro M. P. B. Menge, Edith Gelens, Erwin Snip, Remko A. Bakker, Sylvain Celanire, Michel Gillard, Patrice Talaga, Henk Timmerman, and Rob Leurs
pp 2414–2417Publication Date (Web): April 09, 2004 (Letter)
DOI: 10.1021/jm049932u
Discovery of Diarylacrylonitriles as a Novel Series of Small Molecule Sortase A Inhibitors
Ki-Bong Oh, Soo-Hwan Kim, Jaekwang Lee, Won-Jea Cho, Taeho Lee, and Sanghee Kim
pp 2418–2421Publication Date (Web): March 30, 2004 (Letter)
DOI: 10.1021/jm0498708
Design and Synthesis of α-Aryloxy-α-methylhydrocinnamic Acids: A Novel Class of Dual Peroxisome Proliferator-Activated Receptor α/γ Agonists
Yanping Xu, Christopher J. Rito, Garret J. Etgen, Robert J. Ardecky, James S. Bean, William R. Bensch, Jacob R. Bosley, Carol L. Broderick, Dawn A. Brooks, Samuel J. Dominianni, Patric J. Hahn, Sha Liu, Dale E. Mais, Chahrzad Montrose-Rafizadeh, Kathy M. Ogilvie, Brian A. Oldham, Mary Peters, Deepa K. Rungta, Anthony J. Shuker, Gregory A. Stephenson, Allie E. Tripp, Sarah B. Wilson, Leonard L. Winneroski, Richard Zink, Raymond F. Kauffman, and James R. McCarthy
pp 2422–2425Publication Date (Web): April 10, 2004 (Letter)
DOI: 10.1021/jm0342616
N-Phenylphenylglycines as Novel Corticotropin Releasing Factor Receptor Antagonists
Valentina Molteni, Julie Penzotti, Dean M. Wilson, Andreas P. Termin, Long Mao, Christine M. Crane, Fred Hassman, Tao Wang, Harvey Wong, Keith J. Miller, Scott Grossman, and Peter D. J. Grootenhuis
pp 2426–2429Publication Date (Web): April 10, 2004 (Letter)
DOI: 10.1021/jm049974i
Articles
Discovery of Embelin as a Cell-Permeable, Small-Molecular Weight Inhibitor of XIAP through Structure-Based Computational Screening of a Traditional Herbal Medicine Three-Dimensional Structure Database
Zaneta Nikolovska-Coleska, Liang Xu, Zengjian Hu, York Tomita, Peng Li, Peter P. Roller, Renxiao Wang, Xueliang Fang, Ribo Guo, Manchao Zhang, Marc E. Lippman, Dajun Yang, and Shaomeng Wang
pp 2430–2440Publication Date (Web): April 14, 2004 (Article)
DOI: 10.1021/jm030420+
Full Text HTMLNovel N-Arylpyrazolo[3,2-c]-Based Ligands for the Glucocorticoid Receptor: Receptor Binding and in Vivo Activity
Amjad Ali, Christopher F. Thompson, James M. Balkovec, Donald W. Graham, Milton L. Hammond, Nazia Quraishi, James R. Tata, Monica Einstein, Lan Ge, Georgianna Harris, Terri M. Kelly, Paul Mazur, Shilpa Pandit, Joseph Santoro, Ayesha Sitlani, Chuanlin Wang, Joanne Williamson, Douglas K. Miller, Chris M. Thompson, Dennis M. Zaller, Michael J. Forrest, Ester Carballo-Jane, and Silvi Luell
pp 2441–2452Publication Date (Web): April 02, 2004 (Article)
DOI: 10.1021/jm030585i
5-Substituted Derivatives of 6-Halogeno-3-((2-(S)-azetidinyl)methoxy)pyridine and 6-Halogeno-3-((2-(S)-pyrrolidinyl)methoxy)pyridine with Low Picomolar Affinity for α4β2 Nicotinic Acetylcholine Receptor and Wide Range of Lipophilicity: Potential Probes for Imaging with Positron Emission Tomography
Yi Zhang, Olga A. Pavlova, Svetlana I. Chefer, Andrew W. Hall, Varughese Kurian, LaVerne L. Brown, Alane S. Kimes, Alexey G. Mukhin, and Andrew G. Horti
pp 2453–2465Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm030432v
Reducing the Peptidyl Features of Caspase-3 Inhibitors: A Structural Analysis
Joseph W. Becker, Jennifer Rotonda, Stephen M. Soisson, Renee Aspiotis, Christopher Bayly, Sébastien Francoeur, Michel Gallant, Marga Garcia-Calvo, Andre Giroux, Erich Grimm, Yongxin Han, Dan McKay, Donald W. Nicholson, Erin Peterson, Johanne Renaud, Sophie Roy, Nancy Thornberry, and Robert Zamboni
pp 2466–2474Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm0305523
Synthesis of 2,4-Diamino-6-[2‘-O-(ω-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpteridines as Potent and Selective Inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium Dihydrofolate Reductase
Andre Rosowsky, Hongning Fu, David C. M. Chan, and Sherry F. Queener
pp 2475–2485Publication Date (Web): April 10, 2004 (Article)
DOI: 10.1021/jm030599o
Non-Peptidic Small-Molecule Inhibitors of the Single-Chain Hepatitis C Virus NS3 Protease/NS4A Cofactor Complex Discovered by Structure-Based NMR Screening
Daniel F. Wyss, Ashok Arasappan, Mary M. Senior, Yu-Sen Wang, Brian M. Beyer, F. George Njoroge, and Mark A. McCoy
pp 2486–2498Publication Date (Web): April 09, 2004 (Article)
DOI: 10.1021/jm0305117
Conformational Analysis of Drug-Like Molecules Bound to Proteins: An Extensive Study of Ligand Reorganization upon Binding
Emanuele Perola and Paul S. Charifson
pp 2499–2510Publication Date (Web): April 07, 2004 (Article)
DOI: 10.1021/jm030563w
Peptide-Based Inhibitors of the Hepatitis C Virus NS3 Protease: Structure−Activity Relationship at the C-Terminal Position
Jean Rancourt, Dale R. Cameron, Vida Gorys, Daniel Lamarre, Martin Poirier, Diane Thibeault, and Montse Llinàs-Brunet
pp 2511–2522Publication Date (Web): April 01, 2004 (Article)
DOI: 10.1021/jm030573x
Structure−Function Relationships of Multidrug Resistance P-Glycoprotein
Ilza K. Pajeva, Christoph Globisch, and Michael Wiese
pp 2523–2533Publication Date (Web): April 10, 2004 (Article)
DOI: 10.1021/jm031009p
General Model for Estimation of the Inhibition of Protein Kinases Using Monte Carlo Simulations
Yukio Tominaga and William L. Jorgensen
pp 2534–2549Publication Date (Web): April 02, 2004 (Article)
DOI: 10.1021/jm0304358
Roles of Conformational and Positional Adaptability in Structure-Based Design of TMC125-R165335 (Etravirine) and Related Non-nucleoside Reverse Transcriptase Inhibitors That Are Highly Potent and Effective against Wild-Type and Drug-Resistant HIV-1 Variants
Kalyan Das, Arthur D. Clark, Jr., Paul J. Lewi, Jan Heeres, Marc R. de Jonge, Lucien M. H. Koymans, H. Maarten Vinkers, Frederik Daeyaert, Donald W. Ludovici, Michael J. Kukla, Bart De Corte, Robert W. Kavash, Chih Y. Ho, Hong Ye, Mark. A. Lichtenstein, Koen Andries, Rudi Pauwels, Marie-Pierre de Béthune, Paul L. Boyer, Patrick Clark, Stephen H. Hughes, Paul A. J. Janssen, and Eddy Arnold
pp 2550–2560Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm030558s
Rational Design and Synthesis of Novel Dimeric Diketoacid-Containing Inhibitors of HIV-1 Integrase: Implication for Binding to Two Metal Ions on the Active Site of Integrase
Ya-Qiu Long, Xiao-Hua Jiang, Raveendra Dayam, Tino Sanchez, Robert Shoemaker, Shizuko Sei, and Nouri Neamati
pp 2561–2573Publication Date (Web): April 10, 2004 (Article)
DOI: 10.1021/jm030559k
Design, Synthesis, Structural Studies, Biological Evaluation, and Computational Simulations of Novel Potent AT1 Angiotensin II Receptor Antagonists Based on the 4-Phenylquinoline Structure
Andrea Cappelli, Gal.la Pericot Mohr, Andrea Gallelli, Milena Rizzo, Maurizio Anzini, Salvatore Vomero, Laura Mennuni, Flora Ferrari, Francesco Makovec, M. Cristina Menziani, Pier G. De Benedetti, and Gianluca Giorgi
pp 2574–2586Publication Date (Web): April 10, 2004 (Article)
DOI: 10.1021/jm031100t
Synthesis of Novel Potent Dipeptidyl Peptidase IV Inhibitors with Enhanced Chemical Stability: Interplay between the N-Terminal Amino Acid Alkyl Side Chain and the Cyclopropyl Group of α-Aminoacyl-l-cis-4,5-methanoprolinenitrile-Based Inhibitors
David R. Magnin, Jeffrey A. Robl, Richard B. Sulsky, David J. Augeri, Yanting Huang, Ligaya M. Simpkins, Prakash C. Taunk, David A. Betebenner, James G. Robertson, Benoni E. Abboa-Offei, Aiying Wang, Michael Cap, Li Xin, Li Tao, Doree F. Sitkoff, Mary F. Malley, Jack Z. Gougoutas, Ashish Khanna, Qi Huang, Song-Ping Han, Rex A. Parker, and Lawrence G. Hamann
pp 2587–2598Publication Date (Web): April 13, 2004 (Article)
DOI: 10.1021/jm049924d
Oral Bioavailability of a New Class of μ-Opioid Receptor Agonists Containing 3,6-Bis[Dmt-NH(CH2)n]-2(1H)-pyrazinone with Central-Mediated Analgesia
Yunden Jinsmaa, Anna Miyazaki, Yoshio Fujita, Tingyou Li, Yutaka Fujisawa, Kimitaka Shiotani, Yuko Tsuda, Toshio Yokoi, Akihiro Ambo, Yusuke Sasaki, Sharon D. Bryant, Lawrence H. Lazarus, and Yoshio Okada
pp 2599–2610Publication Date (Web): March 30, 2004 (Article)
DOI: 10.1021/jm0304616
Cytotoxic α-Halogenoacrylic Derivatives of Distamycin A and Congeners
Italo Beria, Pier Giovanni Baraldi, Paolo Cozzi, Marina Caldarelli, Cristina Geroni, Sergio Marchini, Nicola Mongelli, and Romeo Romagnoli
pp 2611–2623Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm031051k
Synthesis and Pharmacological Evaluation of 3-(3,4-Dichlorophenyl)-1-indanamine Derivatives as Nonselective Ligands for Biogenic Amine Transporters
Han Yu, In Jong Kim, John E. Folk, Xinrong Tian, Richard B. Rothman, Michael H. Baumann, Christina M. Dersch, Judith L. Flippen-Anderson, Damon Parrish, Arthur E. Jacobson, and Kenner C. Rice
pp 2624–2634Publication Date (Web): April 14, 2004 (Article)
DOI: 10.1021/jm0305873
Inhibitors of Sir2: Evaluation of Splitomicin Analogues
Jeff Posakony, Maki Hirao, Sam Stevens, Julian A. Simon, and Antonio Bedalov
pp 2635–2644Publication Date (Web): April 09, 2004 (Article)
DOI: 10.1021/jm030473r
Prediction of Biological Targets Using Probabilistic Neural Networks and Atom-Type Descriptors
Tomoko Niwa
pp 2645–2650Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm0302795
Significant Differences in Biological Parameters between Prodrugs Cleavable by Carboxypeptidase G2 That Generate 3,5-Difluoro-phenol and -aniline Nitrogen Mustards in Gene-Directed Enzyme Prodrug Therapy Systems
I. Niculescu-Duvaz, I. Scanlon, D. Niculescu-Duvaz, F. Friedlos, J. Martin, R. Marais, and C. J. Springer
pp 2651–2658Publication Date (Web): April 07, 2004 (Article)
DOI: 10.1021/jm030966w
New Arylpiperazine 5-HT1A Receptor Ligands Containing the Pyrimido[2,1-f]purine Fragment: Synthesis, in Vitro, and in Vivo Pharmacological Evaluation
Sławomir Jurczyk, Marcin Kołaczkowski, Ewa Maryniak, Paweł Zajdel, Maciej Pawłowski, Ewa Tatarczyńska, Aleksandra Kłodzińska, Ewa Chojnacka-Wójcik, Andrzej J. Bojarski, Sijka Charakchieva-Minol, Beata Duszyńska, Gabriel Nowak, and Dorota Macia̧g
pp 2659–2666Publication Date (Web): April 10, 2004 (Article)
DOI: 10.1021/jm030946u
A New Class of Nonpeptide Bradykinin B2 Receptor Ligand, Incorporating a 4-Aminoquinoline Framework. Identification of a Key Pharmacophore To Determine Species Difference and Agonist/Antagonist Profile
Yuki Sawada, Hiroshi Kayakiri, Yoshito Abe, Tsuyoshi Mizutani, Noriaki Inamura, Masayuki Asano, Ichiro Aramori, Chie Hatori, Teruo Oku, and Hirokazu Tanaka
pp 2667–2677Publication Date (Web): April 01, 2004 (Article)
DOI: 10.1021/jm030326t
4-(ω-(Alkyloxy)alkyl)-1H-imidazole Derivatives as Histamine H3 Receptor Antagonists/Agonists
Galina Meier, Michael Krause, Annette Hüls, Xavier Ligneau, Heinz H. Pertz, Jean-Michel Arrang, C. Robin Ganellin, Jean-Charles Schwartz, Walter Schunack, and Holger Stark
pp 2678–2687Publication Date (Web): April 14, 2004 (Article)
DOI: 10.1021/jm031065q
New 1,4-Dihydropyridines Endowed with NO-Donor and Calcium Channel Agonist Properties
Sonja Visentin, Barbara Rolando, Antonella Di Stilo, Roberta Fruttero, Monica Novara, Emilio Carbone, Christian Roussel, Nicolas Vanthuyne, and Alberto Gasco
pp 2688–2693Publication Date (Web): April 01, 2004 (Article)
DOI: 10.1021/jm031109v
Fluoroartemisinin: Trifluoromethyl Analogues of Artemether and Artesunate
Guillaume Magueur, Benoit Crousse, Sébastien Charneau, Philippe Grellier, Jean-Pierre Bégué, and Danièle Bonnet-Delpon
pp 2694–2699Publication Date (Web): April 06, 2004 (Article)
DOI: 10.1021/jm0310333
Parallel Solution-Phase Synthesis of Conformationally Restricted Congeners of Pentamidine and Evaluation of Their Antiplasmodial Activities
Annie Mayence, Jean Jacques Vanden Eynde, Fran M. Krogstad, Donald J. Krogstad, Melanie T. Cushion, and Tien L. Huang
pp 2700–2705Publication Date (Web): April 14, 2004 (Article)
DOI: 10.1021/jm030545e
Brief Articles
[1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a Bioisostere of a Carboxylic Acid Aldose Reductase Inhibitor
Ioannis Nicolaou, Chariklia Zika, and Vassilis J. Demopoulos
pp 2706–2709Publication Date (Web): April 09, 2004 (Brief Article)
DOI: 10.1021/jm031060t
Synthesis and Use of Novel Ether Phospholipid Enantiomers To Probe the Molecular Basis of the Antitumor Effects of Alkyllysophospholipids: Correlation of Differential Activation of c-Jun NH2-Terminal Protein Kinase with Antiproliferative Effects in Neuronal Tumor Cells
Pranati Samadder, Robert Bittman, Hoe-Sup Byun, and Gilbert Arthur
pp 2710–2713Publication Date (Web): April 03, 2004 (Brief Article)
DOI: 10.1021/jm0302748
Book Reviews
Hydrolysis in Drug and Prodrug Metabolism. Chemistry, Biochemistry, and Enzymology By Bernard Testa and Joachim M. Mayer. Wiley-VCH, Zürich, Switzerland. 2003. xx + 780 pp. 18 × 24.5 cm. ISBN 3-906390-25-X. $215.00
Michael W. Duffel
pp 2714–2715Publication Date (Web): April 10, 2004 (Book Review)
DOI: 10.1021/jm040043g
Drug Discovery Strategies and Methods Edited by Alexandros Makriyannis and Diane Biegel. Marcel Dekker, New York. 2004. xi + 348 pp. 16 × 23.5 cm. ISBN 0-8247-0691-9. $174.00.
p 2714Publication Date (Web): March 30, 2004 (Book Review)
DOI: 10.1021/jm0400449
Additions and Corrections
Identification of Opioid Ligands Possessing Mixed μ Agonist/δ Antagonist Activity among Pyridomorphinans Derived from Naloxone, Oxymorphone, and Hydromorphone.
Subramaniam Ananthan, Naveen K. Khare, Surendra K. Saini, Lainne E. Seitz, Jeffrey L. Bartlett, Peg Davis, Christina M. Dersch, Frank Porreca, Richard B. Rothman, and Edward J. Bilsky:
p 2716Publication Date (Web): April 02, 2004 (Addition/Correction)
DOI: 10.1021/jm0400597
Inhibitors of Serine Proteases as Potential Therapeutic Agents: The Road from Thrombin to Tryptase to Cathepsin G.
Bruce E. Maryanoff:
p 2716Publication Date (Web): April 03, 2004 (Addition/Correction)
DOI: 10.1021/jm040064a