Table of Contents

January 22, 2009
Volume 52, Issue 2
Pages 225-580

Perspectives

Beyond Picomolar Affinities: Quantitative Aspects of Noncovalent and Covalent Binding of Drugs to Proteins

Adam J. T. Smith, Xiyun Zhang, Andrew G. Leach and K. N. Houk*
pp 225–233
Publication Date (Web): November 21, 2008 (Perspective)
DOI: 10.1021/jm800498e

Letters

Discovery of 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic Acid Amide Hydrochloride (CP-945,598), a Novel, Potent, and Selective Cannabinoid Type 1 Receptor Antagonist

David A. Griffith*, John R. Hadcock, Shawn C. Black, Philip A. Iredale, Philip A. Carpino, Paul DaSilva-Jardine, Robert Day, Joseph DiBrino, Robert L. Dow, Margaret S. Landis, Rebecca E. O’Connor and Dennis O. Scott
pp 234–237
Publication Date (Web): December 22, 2008 (Letter)
DOI: 10.1021/jm8012932

Total Synthesis and Biological Evaluation of Tubulysin U, Tubulysin V, and Their Analogues

Ranganathan Balasubramanian, Bhooma Raghavan, Adrian Begaye, Dan L. Sackett and Robert A. Fecik*
pp 238–240
Publication Date (Web): December 22, 2008 (Letter)
DOI: 10.1021/jm8013579

Articles

Pt(II) Complexes of a Combretastatin A-4 Analogous Chalcone: Effects of Conjugation on Cytotoxicity, Tumor Specificity, and Long-Term Tumor Growth Suppression

Rainer Schobert*, Bernhard Biersack, Andrea Dietrich§, Sebastian Knauer, Miroslava Zoldakova, Angelika Fruehauf§ and Thomas Mueller§
pp 241–246
Publication Date (Web): December 22, 2008 (Article)
DOI: 10.1021/jm801001d

Induced Association of μ Opioid (MOP) and Type 2 Cholecystokinin (CCK2) Receptors by Novel Bivalent Ligands

Yaguo Zheng, Eyup Akgn, Kaleeckal G. Harikumar, Jessika Hopson, Michael D. Powers, Mary M. Lunzer, Laurence J. Miller* and Philip S. Portoghese*
pp 247–258
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm800174p

Inhibition of MDR1 Activity in Vitro by a Novel Class of Diltiazem Analogues: Toward New Candidates

Maurizio Viale, Cinzia Cordazzo, Barbara Cosimelli§, Daniela de Totero, Patrizio Castagnola, Cinzia Aiello, Elda Severi§, Giovanni Petrillo, Maurizio Cianfriglia and Domenico Spinelli*#
pp 259–266
Publication Date (Web): December 18, 2008 (Article)
DOI: 10.1021/jm801195k

Mechanism of p300 Specific Histone Acetyltransferase Inhibition by Small Molecules

M. Arif, Suman Kalyan Pradhan, Thanuja G R, B. M. Vedamurthy, Shipra Agrawal§, Dipak Dasgupta and Tapas K. Kundu*
pp 267–277
Publication Date (Web): December 16, 2008 (Article)
DOI: 10.1021/jm800657z

Design, Structure−Activity Relationships and in Vivo Characterization of 4-Amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A Novel Class of Receptor Tyrosine Kinase Inhibitors

Paul A. Renhowe*, Sabina Pecchi, Cynthia M. Shafer, Timothy D. Machajewski, Elisa M. Jazan, Clarke Taylor, William Antonios-McCrea, Christopher M. McBride, Kelly Frazier, Marion Wiesmann, Gena R. Lapointe, Paul H. Feucht, Robert L. Warne, Carla C. Heise, Daniel Menezes, Kimberly Aardalen, Helen Ye, Molly He, Vincent Le, Jayesh Vora, Johanna M. Jansen, Mary Ellen Wernette-Hammond and Alex L. Harris
pp 278–292
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm800790t

First Cdc7 Kinase Inhibitors: Pyrrolopyridinones as Potent and Orally Active Antitumor Agents. 2. Lead Discovery

Maria Menichincheri, Alberto Bargiotti, Jens Berthelsen, Jay A. Bertrand, Roberto Bossi, Antonella Ciavolella, Alessandra Cirla, Cinzia Cristiani, Valter Croci, Roberto D’Alessio, Marina Fasolini, Francesco Fiorentini, Barbara Forte, Antonella Isacchi, Katia Martina§, Antonio Molinari§, Alessia Montagnoli, Paolo Orsini, Fabrizio Orzi, Enrico Pesenti, Daniele Pezzetta, Antonio Pillan, Italo Poggesi, Fulvia Roletto, Alessandra Scolaro, Marco Tat, Marcellino Tibolla, Barbara Valsasina, Mario Varasi, Daniele Volpi, Corrado Santocanale# and Ermes Vanotti*
pp 293–307
Publication Date (Web): December 30, 2008 (Article)
DOI: 10.1021/jm800977q

Structural Analysis of ARC-Type Inhibitor (ARC-1034) Binding to Protein Kinase A Catalytic Subunit and Rational Design of Bisubstrate Analogue Inhibitors of Basophilic Protein Kinases

Darja Lavogina, Marje Lust, Indrek Viil, Norbert Knig, Gerda Raidaru, Jevgenia Rogozina, Erki Enkvist, Asko Uri* and Dirk Bossemeyer
pp 308–321
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm800797n

Carbonic Anhydrase Inhibitors. Comparison of Chlorthalidone and Indapamide X-ray Crystal Structures in Adducts with Isozyme II: When Three Water Molecules and the Keto−Enol Tautomerism Make the Difference

Claudia Temperini, Alessandro Cecchi, Andrea Scozzafava and Claudiu T. Supuran*
pp 322–328
Publication Date (Web): December 30, 2008 (Article)
DOI: 10.1021/jm801386n

Metabolic Soft Spot Identification and Compound Optimization in Early Discovery Phases Using MetaSite and LC-MS/MS Validation

Markus Trunzer, Bernard Faller and Alfred Zimmerlin*
pp 329–335
Publication Date (Web): December 24, 2008 (Article)
DOI: 10.1021/jm8008663

Discovery and Structure−Activity Relationship of P1−P3 Ketoamide Derived Macrocyclic Inhibitors of Hepatitis C Virus NS3 Protease

Srikanth Venkatraman*, Francisco Velazquez, Wanli Wu, Melissa Blackman, Kevin X. Chen, Stephane Bogen, Latha Nair, Xiao Tong, Robert Chase, Andrea Hart, Sony Agrawal, John Pichardo, Andrew Prongay, Kuo-Chi Cheng, Viyyoor Girijavallabhan, John Piwinski, Neng-Yang Shih and F. George Njoroge
pp 336–346
Publication Date (Web): December 22, 2008 (Article)
DOI: 10.1021/jm800940u

A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes for Targeting Prostate Cancer

K. P. Maresca, S. M. Hillier, F. J. Femia, D. Keith, C. Barone, J. L. Joyal, C. N. Zimmerman, A. P. Kozikowski, J. A. Barrett, W. C. Eckelman and J. W. Babich*
pp 347–357
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm800994j

Photodynamic Molecular Beacon Triggered by Fibroblast Activation Protein on Cancer-Associated Fibroblasts for Diagnosis and Treatment of Epithelial Cancers

Pui-Chi Lo, Juan Chen, Klara Stefflova§, Michael S. Warren§, Roya Navab, Bizhan Bandarchi, Stefanie Mullins, Ming Tsao, Jonathan D. Cheng and Gang Zheng*#
pp 358–368
Publication Date (Web): December 18, 2008 (Article)
DOI: 10.1021/jm801052f

Discovery of Novel CB2 Receptor Ligands by a Pharmacophore-Based Virtual Screening Workflow

Patrick Markt, Clemens Feldmann, Judith Maria Rollinger, Stefan Raduner§, Daniela Schuster, Johannes Kirchmair, Simona Distinto, Gudrun Maria Spitzer#, Gerhard Wolber*, Christian Laggner, Karl-Heinz Altmann§, Thierry Langer and Jrg Gertsch§
pp 369–378
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm801044g

Fragment-Based Discovery of the Pyrazol-4-yl Urea (AT9283), a Multitargeted Kinase Inhibitor with Potent Aurora Kinase Activity

Steven Howard*, Valerio Berdini, John A. Boulstridge, Maria G. Carr, David M. Cross, Jayne Curry, Lindsay A. Devine, Theresa R. Early, Lynsey Fazal, Adrian L. Gill, Michelle Heathcote, Sarita Maman, Julia E. Matthews, Rachel L. McMenamin, Eva F. Navarro, Michael A. O’Brien, Marc O’Reilly, David C. Rees, Matthias Reule, Dominic Tisi, Glyn Williams, Mladen Vinkoviand Paul G. Wyatt
pp 379–388
Publication Date (Web): December 30, 2008 (Article)
DOI: 10.1021/jm800984v

Crystal Structure of the Homo sapiens Kynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity

Santiago Lima, Sunil Kumar§, Vijay Gawandi§, Cory Momany and Robert S. Phillips*§
pp 389–396
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm8010806

Four-Dimensional Docking: A Fast and Accurate Account of Discrete Receptor Flexibility in Ligand Docking

Giovanni Bottegoni, Irina Kufareva, Maxim Totrov and Ruben Abagyan*
pp 397–406
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm8009958

Iron Chelators of the Dipyridylketone Thiosemicarbazone Class: Precomplexation and Transmetalation Effects on Anticancer Activity

Paul V. Bernhardt*§, Philip C. Sharpe§, Mohammad Islam§, David B. Lovejoy, Danuta S. Kalinowski and Des R. Richardson*
pp 407–415
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm801012z

Discovery of Human Macrophage Migration Inhibitory Factor (MIF)-CD74 Antagonists via Virtual Screening

Zoe Cournia, Lin Leng, Sunilkumar Gandavadi, Xin Du, Richard Bucala* and William L. Jorgensen*
pp 416–424
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm801100v

Dual Integrin and Gastrin-Releasing Peptide Receptor Targeted Tumor Imaging Using 18F-labeled PEGylated RGD-Bombesin Heterodimer 18F-FB-PEG3-Glu-RGD-BBN

Zhaofei Liu§, Yongjun Yan§, Frederic T. Chin, Fan Wang and Xiaoyuan Chen*
pp 425–432
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm801285t

6-Methoxy-N-alkyl Isatin Acylhydrazone Derivatives as a Novel Series of Potent Selective Cannabinoid Receptor 2 Inverse Agonists: Design, Synthesis, and Binding Mode Prediction

Philippe Diaz, Sharangdhar S. Phatak, Jijun Xu, Fanny Astruc-Diaz, Claudio N. Cavasotto and Mohamed Naguib*
pp 433–444
Publication Date (Web): December 30, 2008 (Article)
DOI: 10.1021/jm801353p

Comparative Positron-Emission Tomography (PET) Imaging and Phototherapeutic Potential of 124I- Labeled Methyl- 3-(1′-iodobenzyloxyethyl)pyropheophorbide-a vs the Corresponding Glucose and Galactose Conjugates

Suresh K. Pandey, Munawwar Sajjad*, Yihui Chen, Xiang Zheng, Rutao Yao, Joseph R. Missert, Carrie Batt, Hani A. Nabi, Allan R. Oseroff§ and Ravindra K. Pandey*
pp 445–455
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm8012213

Non-Peptide Macrocyclic Histone Deacetylase Inhibitors

Adegboyega K. Oyelere*§, Po C. Chen, William Guerrant, Sandra C. Mwakwari, Rebecca Hood#, Yunzhe Zhang and Yuhong Fan§
pp 456–468
Publication Date (Web): December 18, 2008 (Article)
DOI: 10.1021/jm801128g

Detection and Assignment of Common Scaffolds in Project Databases of Lead Molecules

Alex M. Clark* and Paul Labute
pp 469–483
Publication Date (Web): December 18, 2008 (Article)
DOI: 10.1021/jm801098a

Synthesis, Oxidant Properties, and Antitumoral Effects of a Heteroleptic Palladium(II) Complex of Curcumin on Human Prostate Cancer Cells

Alessandra Valentini*, Franco Conforti, Alessandra Crispini, Angelo De Martino§, Rossella Condello, Chiara Stellitano, Giuseppe Rotilio§, Mauro Ghedini, Giorgio Federici, Sergio Bernardini and Daniela Pucci
pp 484–491
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm801276a

Berberine Analogues as a Novel Class of the Low-Density-Lipoprotein Receptor Up-Regulators: Synthesis, Structure−Activity Relationships, and Cholesterol-Lowering Efficacy

Ying-Hong Li, Peng Yang, Wei-Jia Kong, Yan-Xiang Wang, Chang-Qin Hu§, Zeng-Yan Zuo, Yue-Ming Wang, Hong Gao, Li-Mei Gao, Yan-Chun Feng§, Na-Na Du, Ying Liu, Dan-Qing Song* and Jian-Dong Jiang*
pp 492–501
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm801157z

Combining 4-Aminoquinoline- and Clotrimazole-Based Pharmacophores toward Innovative and Potent Hybrid Antimalarials

Sandra Gemma, Giuseppe Campiani*, Stefania Butini, Bhupendra P. Joshi, Gagan Kukreja, Salvatore Sanna Coccone, Matteo Bernetti, Marco Persico§, Vito Nacci, Isabella Fiorini, Ettore Novellino, Donatella Taramelli#, Nicoletta Basilico#, Silvia Parapini#, Vanessa Yardley, Simon Croft, Sonja Keller-Maerki×, Matthias Rottmann×, Reto Brun×, Massimiliano Coletta, Stefano Marini, Giovanna Guiso, Silvio Caccia and Caterina Fattorusso§
pp 502–513
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm801352s

Discovery of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the Treatment of Cancer

Thomas D. Penning*, Gui-Dong Zhu, Viraj B. Gandhi, Jianchun Gong, Xuesong Liu, Yan Shi, Vered Klinghofer, Eric F. Johnson, Cherrie K. Donawho, David J. Frost, Velitchka Bontcheva-Diaz, Jennifer J. Bouska, Donald J. Osterling, Amanda M. Olson, Kennan C. Marsh, Yan Luo and Vincent L. Giranda
pp 514–523
Publication Date (Web): December 22, 2008 (Article)
DOI: 10.1021/jm801171j

Synthesis and Biological Activity of Human Neuropeptide S Analogues Modified in Position 5: Identification of Potent and Pure Neuropeptide S Receptor Antagonists

Remo Guerrini*, Valeria Camarda, Claudio Trapella, Girolamo Calò, Anna Rizzi, Chiara Ruzza, Stella Fiorini, Erika Marzola, Rainer K. Reinscheid§, Domenico Regoli and Severo Salvadori
pp 524–529
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm8012294

A Novel Histone Acetyltransferase Inhibitor Modulating Gcn5 Network: Cyclopentylidene-[4-(4′-chlorophenyl)thiazol-2-yl)hydrazone

Franco Chimenti, Bruna Bizzarri*, Elias Maccioni, Daniela Secci, Adriana Bolasco, Paola Chimenti, Rossella Fioravanti, Arianna Granese, Simone Carradori, Federica Tosi§, Paola Ballario§, Stefano Vernarecci and Patrizia Filetici
pp 530–536
Publication Date (Web): December 17, 2008 (Article)
DOI: 10.1021/jm800885d

Synthesis and Biological Studies of Different Duocarmycin Based Glycosidic Prodrugs for Their Use in the Antibody-Directed Enzyme Prodrug Therapy

Lutz F. Tietze*, Heiko J. Schuster, Birgit Krewer and Ingrid Schuberth
pp 537–543
Publication Date (Web): December 29, 2008 (Article)
DOI: 10.1021/jm8009102

Multivalent Scaffolds for Affinity Maturation of Small Molecule Cell Surface Binders and Their Application to Prostate Tumor Targeting

Valerie Humblet#, Preeti Misra#, Kumar R. Bhushan#, Khaled Nasr#, Yao-Sen Ko§, Takashi Tsukamoto§, Nadine Pannier, John V. Frangioni* and Wolfgang Maison*#
pp 544–550
Publication Date (Web): December 24, 2008 (Article)
DOI: 10.1021/jm801033c

Oligodeoxyribonucleotide-Based Antagonists for Toll-Like Receptors 7 and 9

Daqing Wang, Lakshmi Bhagat, Dong Yu, Fu-Gang Zhu, Jimmy X. Tang, Ekambar R. Kandimalla and Sudhir Agrawal*
pp 551–558
Publication Date (Web): December 22, 2008 (Article)
DOI: 10.1021/jm8014316

Brief Articles

Codrugs Linking l-Dopa and Sulfur-Containing Antioxidants: New Pharmacological Tools against Parkinson’s Disease

Francesco Pinnen, Ivana Cacciatore, Catia Cornacchia, Piera Sozio, Laura Serafina Cerasa, Antonio Iannitelli, Cinzia Nasuti, Franco Cantalamessa, Durairaj Sekar, Rosita Gabbianelli§, Maria Letizia Falcioni§ and Antonio Di Stefano*
pp 559–563
Publication Date (Web): December 18, 2008 (Brief Article)
DOI: 10.1021/jm801266x

Identification of a New G-Quadruplex Motif in the KRAS Promoter and Design of Pyrene-Modified G4-Decoys with Antiproliferative Activity in Pancreatic Cancer Cells

Susanna Cogoi, Manikandan Paramasivam, Vyacheslav Filichev, Imrich Gci§, Erik B. Pedersen§ and Luigi E. Xodo*
pp 564–568
Publication Date (Web): December 19, 2008 (Brief Article)
DOI: 10.1021/jm800874t

Docking Studies on a New Human Immodeficiency Virus Integrase−Mg−DNA Complex: Phenyl Ring Exploration and Synthesis of 1H-Benzylindole Derivatives through Fluorine Substitutions

Stefania Ferro, Laura De Luca, Maria Letizia Barreca, Nunzio Iraci, Sara De Grazia, Frauke Christ, Myriam Witvrouw, Zeger Debyser and Alba Chimirri*
pp 569–573
Publication Date (Web): December 23, 2008 (Brief Article)
DOI: 10.1021/jm8009266

Edaravone Derivatives Containing NO-Donor Functions

Konstantin Chegaev, Clara Cena, Marta Giorgis, Barbara Rolando, Paolo Tosco, Massimo Bertinaria, Roberta Fruttero, Pierre-Alain Carrupt and Alberto Gasco*
pp 574–578
Publication Date (Web): December 29, 2008 (Brief Article)
DOI: 10.1021/jm8007008

Book Reviews

Book Review of Molecular Drug Properties: Measurement and Prediction

Donald F. Weaver
p 579
Publication Date (Web): December 11, 2008 (Book Review)
DOI: 10.1021/jm801425w

Book Review of Arrow Pushing in Organic Chemistry: An Easy Approach to Understanding Organic Reaction Mechanisms

Chris Schwartz and Patrick Dussault*
pp 579–580
Publication Date (Web): December 3, 2008 (Book Review)
DOI: 10.1021/jm801461g