Perspectives

Development of the Renal Glucose Reabsorption Inhibitors: A New Mechanism for the Pharmacotherapy of Diabetes Mellitus Type 2 William N. Washburn† 1785-1794 Full: PDF (895 K)

Letters

Antiseizure Activity of Novel γ-Aminobutyric Acid (A) Receptor Subtype-Selective Benzodiazepine Analogues in Mice and Rat Models Felix M. Rivas†, James P. Stables‡, Lauren Murphree‡, Rahul V. Edwankar†, Chitra R. Edwankar†, Shengming Huang†, Hiteshkumar D. Jain†, Hao Zhou†, Samarpan Majumder§, Subramanian Sankar, Bryan L. Roth§, Joachim Ramerstorfer, Roman Furtmüller, Werner Sieghart and James M. Cook*† 1795-1798 Full: PDF (157 K)

A Selective Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Chronic Obstructive Pulmonary Disease (COPD): Discovery of (S)-2-(8-(Methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408) Wei Li*†, Jianchang Li†, Yuchuan Wu†, Junjun Wu†, Rajeev Hotchandani†, Kristina Cunningham†, Iain McFadyen†, Joel Bard†, Paul Morgan‡, Franklin Schlerman‡, Xin Xu§, Steve Tam†, Samuel J. Goldman‡, Cara Williams‡, Joseph Sypek‡ and Tarek S. Mansour† 1799-1802 Full: PDF (302 K)

Articles

Comparison of N-Terminal Modifications on Neurotensin(8−13) Analogues Correlates Peptide Stability but Not Binding Affinity with in Vivo Efficacy Kevin S. Orwig†, McKensie R. Lassetter†, M. Kyle Hadden† and Thomas A. Dix*†‡ 1803-1813 Full: PDF (591 K)

Hit to Lead Account of the Discovery of a New Class of Inhibitors of Pim Kinases and Crystallographic Studies Revealing an Unusual Kinase Binding Mode† Kevin Qian‡, Lian Wang‡, Charles L. Cywin, Bennett T. Farmer, , Eugene Hickey, Carol Homon, Scott Jakes, Mohammed A. Kashem, George Lee, Scott Leonard, Jun Li, Ronald Magboo, Wang Mao, Edward Pack, Charlene Peng, Anthony Prokopowicz, , Morgan Welzel§, John Wolak and Tina Morwick* 1814-1827 Full: PDF (763 K)

Synthesis, Antimalarial Activity, and Preclinical Pharmacology of a Novel Series of 4′-Fluoro and 4′-Chloro Analogues of Amodiaquine. Identification of a Suitable “Back-Up” Compound for N-tert-Butyl Isoquine Paul M. O’Neill*†‡, Alison E. Shone‡, Deborah Stanford†, Gemma Nixon†, Eghbaleh Asadollahy†, B. Kevin Park‡, James L. Maggs‡, Phil Roberts‡, Paul A. Stocks†, Giancarlo Biagini§, Patrick G. Bray§, Jill Davies§, Neil Berry†, Charlotte Hall§, Karen Rimmer§, Peter A. Winstanley‡, Stephen Hindley†, Ramesh B. Bambal, Charles B. Davis, Martin Bates, Stephanie L. Gresham#, Richard A. Brigandi, Federico M. Gomez-de-las-Heras, Domingo V. Gargallo, Silvia Parapini¶, Livia Vivas, Hollie Lander, Donatella Taramelli¶ and Stephen A. Ward§ 1828-1844 Full: PDF (1176 K)

Novel Isothiourea Derivatives as Potent Neuroprotectors and Cognition Enhancers: Synthesis, Biological and Physicochemical Properties German L. Perlovich*†‡, Alexey N. Proshin‡, Tatyana V. Volkova†, Sergey V. Kurkov†, Vlaimir V. Grigoriev‡, Ludmila N. Petrova‡ and Sergey O. Bachurin‡ 1845-1852 Full: PDF (277 K)

From a Natural Product Lead to the Identification of Potent and Selective Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells Irina N. Gaisina†, Franck Gallier†, Andrei V. Ougolkov‡, Ki H. Kim†, Toru Kurome†, Songpo Guo†, Denise Holzle§, Doris N. Luchini‡, Sylvie Y. Blond§, Daniel D. Billadeau*‡ and Alan P. Kozikowski*† 1853-1863 Full: PDF (1146 K)

Identification of a Metabolically Stable Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Antimalarial Activity in Mice Ramesh Gujjar†, Alka Marwaha†, Farah El Mazouni‡, John White†, Karen L. White§, Sharon Creason, David M. Shackleford§, Jeffrey Baldwin‡, William N. Charman§, Frederick S. Buckner, Susan Charman§, Pradipsinh K. Rathod*† and Margaret A. Phillips*‡ 1864-1872 Full: PDF (491 K)

Synthesis of Casimiroin and Optimization of Its Quinone Reductase 2 and Aromatase Inhibitory Activities Arup Maiti†, P. V. Narasimha Reddy†, Megan Sturdy‡, Laura Marler§, Scott D. Pegan‡, Andrew D. Mesecar‡, John M. Pezzuto§ and Mark Cushman*† 1873-1884 Full: PDF (859 K)

Selective 5-Hydroxytryptamine 2C Receptor Agonists Derived from the Lead Compound Tranylcypromine: Identification of Drugs with Antidepressant-Like Action Sung Jin Cho†§, Niels H. Jensen‡§, Toru Kurome†, Sudhakar Kadari†, Michael L. Manzano, Jessica E. Malberg, Barbara Caldarone, Bryan L. Roth*‡ and Alan P. Kozikowski*† 1885-1902 Full: PDF (537 K)

Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB Pathways Jau-Chen Lin†#, Shuenn-Chen Yang†#, Tse-Ming Hong‡, Sung-Liang Yu‡, Qian Shi§, Linyi Wei§, Hsuan-Yu Chen, Pan-Chyr Yang*∞ and Kuo-Hsiung Lee§∞ 1903-1911 Full: PDF (1684 K)

Inhibition of Heat Shock Induction of Heat Shock Protein 70 and Enhancement of Heat Shock Protein 27 Phosphorylation by Quercetin Derivatives Rongsheng E. Wang†, Jeffrey L.-F. Kao†, Carolyn A. Hilliard‡, Raj K. Pandita‡, Joseph L. Roti Roti‡, Clayton R. Hunt‡ and John-Stephen Taylor*† 1912-1921 Full: PDF (535 K)

Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus Francesco Piscitelli†, Antonio Coluccia, Andrea Brancale, Giuseppe La Regina†, Anna Sansone†, Cesare Giordano, Jan Balzarini∞, Giovanni Maga‡, Samantha Zanoli‡, Alberta Samuele‡, Roberto Cirilli#, Francesco La Torre#, Antonio Lavecchia§, Ettore Novellino§ and Romano Silvestri*† 1922-1934 Full: PDF (500 K)

Synthesis, Molecular Modeling, and Selective Inhibitory Activity against Human Monoamine Oxidases of 3-Carboxamido-7-Substituted Coumarins† Franco Chimenti‡, Daniela Secci*‡, Adriana Bolasco‡, Paola Chimenti‡, Bruna Bizzarri‡, Arianna Granese‡, Simone Carradori‡, Matilde Yanez§, Francisco Orallo§, Francesco Ortuso and Stefano Alcaro 1935-1942 Full: PDF (938 K)

Design, Synthesis, and Structure−Activity Relationship of Substrate Competitive, Selective, and in Vivo Active Triazole and Thiadiazole Inhibitors of the c-Jun N-Terminal Kinase Surya K. De†, John L. Stebbins†, Li-Hsing Chen†, Megan Riel-Mehan†, Thomas Machleidt‡, Russell Dahl†, Hongbin Yuan†, Aras Emdadi†, Elisa Barile†, Vida Chen†, Ria Murphy† and Maurizio Pellecchia*† 1943-1952 Full: PDF (725 K)

Novel Chemical Space Exploration via Natural Products Josefin Rosen*†, Johan Gottfries‡, Sorel Muresan§, Anders Backlund† and Tudor I. Oprea 1953-1962 Full: PDF (997 K)

Antioxidant-Based Lead Discovery for Cancer Chemoprevention: The Case of Resveratrol Yi-Ping Qian, Yu-Jun Cai*‡, Gui-Juan Fan, Qing-Yi Wei, Jie Yang, Li-Fang Zheng, Xiu-Zhuang Li, Jian-Guo Fang and Bo Zhou* 1963-1974 Full: PDF (1779 K)

Synthesis and Evaluation of Dibenzothiazepines: A Novel Class of Selective Cannabinoid-1 Receptor Inverse Agonists Hanna Pettersson†, Anne Bulow†, Fredrik Ek†, Jacob Jensen†, Lars K. Ottesen†, Alma Fejzic†, Jian-Nong Ma#, Andria L. Del Tredici#, Erika A. Currier#, Luis R. Gardell#, Ali Tabatabaei#, Darren Craig#, Krista McFarland#, Thomas R. Ott#, Fabrice Piu#, Ethan S. Burstein# and Roger Olsson*† 1975-1982 Full: PDF (594 K)

Lipophilic Lysine−Spermine Conjugates Are Potent Polyamine Transport Inhibitors for Use in Combination with a Polyamine Biosynthesis Inhibitor Mark R. Burns*†, Gerard F. Graminski†, Reitha S. Weeks†, Yan Chen§ and Thomas G. O’Brien§ 1983-1993 Full: PDF (1709 K)

Novel Tricyclic Inhibitors of IκB Kinase James Kempson*†, Steven H. Spergel†, Junqing Guo†, Claude Quesnelle†, Patrice Gill†, Dominique Belanger†, Alaric J. Dyckman†, Tianle Li†, Scott H. Watterson†, Charles M. Langevine†, Jagabandhu Das†, Robert V. Moquin†, Joseph A. Furch†, Anne Marinier†, Marco Dodier†, Alain Martel†, David Nirschl¶, Katy Van Kirk¶, James R. Burke‡, Mark A. Pattoli‡, Kathleen Gillooly‡, Kim W. McIntyre‡, Laishun Chen§, Zheng Yang§, Punit H. Marathe§, David Wang-Iverson§, John H. Dodd†, Murray McKinnon‡, Joel C. Barrish† and William J. Pitts† 1994-2005 Full: PDF (357 K)

Identification of Novel Antibacterial Peptides by Chemoinformatics and Machine Learning† Christopher D. Fjell*§#, Håvard Jenssen#, Kai Hilpert#, Warren A. Cheung§, Nelly Pante, Robert E. W. Hancock# and Artem Cherkasov§ 2006-2015 Full: PDF (1072 K)

Structure−Activity Study of Pentamidine Analogues as Antiprotozoal Agents Svetlana M. Bakunova†, Stanislav A. Bakunov†, Donald A. Patrick†, E. V. K. Suresh Kumar†, Kwasi A. Ohemeng†, Arlene S. Bridges†, Tanja Wenzler‡, Todd Barszcz§, Susan Kilgore Jones†, Karl A. Werbovetz§, Reto Brun‡ and Richard R. Tidwell*† 2016-2035 Full: PDF (284 K)

Substituted Terphenyl Compounds as the First Class of Low Molecular Weight Allosteric Inhibitors of the Luteinizing Hormone Receptor Laura H. Heitman*, Rajeshwar Narlawar, Henk de Vries, Milou N. Willemsen, Dieter Wolfram, Johannes Brussee and Adriaan P. IJzerman 2036-2042 Full: PDF (155 K)

Allosteric Modulation of the Dopamine D2 Receptor by Pro-Leu-Gly-NH2 Peptidomimetics Constrained in Either a Polyproline II Helix or a Type II β-Turn Conformation Bhooma Raghavan†, Kevin J. Skoblenick‡, Swapna Bhagwanth†, Niran Argintaru‡, Ram K. Mishra‡ and Rodney L. Johnson*† 2043-2051 Full: PDF (365 K)

Synthesis and Antibacterial Activities of N-Glycosylated Derivatives of Tyrocidine A, a Macrocyclic Peptide Antibiotic Honggang Hu†‡, Jie Xue†, Benjamin M. Swarts†, Qianli Wang†, Qiuye Wu*‡ and Zhongwu Guo*† 2052-2059 Full: PDF (644 K)

Crystal Structures of Constitutive Nitric Oxide Synthases in Complex with De Novo Designed Inhibitors† Jotaro Igarashi‡, Huiying Li‡, Joumana Jamal‡, Haitao Ji§, Jianguo Fang§, Graham R. Lawton§, Richard B. Silverman§ and Thomas L. Poulos*‡ 2060-2066 Full: PDF (1291 K)

Promiscuous Aggregate-Based Inhibitors Promote Enzyme Unfolding Kristin E. D. Coan†‡, David A. Maltby§‡, Alma L. Burlingame*§ and Brian K. Shoichet*† 2067-2075 Full: PDF (1075 K)

Novel Approach for Chemotype Hopping Based on Annotated Databases of Chemically Feasible Fragments and a Prospective Case Study: New Melanin Concentrating Hormone Antagonists Julen Oyarzabal*†§, Trevor Howe#, Jesus Alcazar, Jose Ignacio Andres, Rosa M. Alvarez§, Frank Dautzenberg, Laura Iturrino, Sonia Martinez§ and Ilse Van der Linden 2076-2089 Full: PDF (1825 K)

Effect of Ring Size on Conformation and Biological Activity of Cyclic Cationic Antimicrobial Peptides Masoud Jelokhani-Niaraki*†, Leslie H. Kondejewski‡, Laura C. Wheaton† and Robert S. Hodges§ 2090-2097 Full: PDF (834 K)

Novel 2- and 4-Substituted 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as Allosteric Modulators of the A3 Adenosine Receptor Yoonkyung Kim†‡§, Sonia de Castro†‡, Zhan-Guo Gao†, Adriaan P. IJzerman and Kenneth A. Jacobson*† 2098-2108 Full: PDF (214 K)

Structure−Activity Relationships for a Series of Quinoline-Based Compounds Active against Replicating and Nonreplicating Mycobacterium tuberculosis Annamaria Lilienkampf†, Jialin Mao†‡, Baojie Wan‡, Yuehong Wang‡, Scott G. Franzblau*‡ and Alan P. Kozikowski*† 2109-2118 Full: PDF (179 K)

Allopregnanolone (3α-Hydroxy-5α-pregnan-20-one) Derivatives with a Polar Chain in Position 16α: Synthesis and Activity Barbora Slavikova†, Zdena Kristofikova‡, Hana Chodounska†, Milos Budesinsky†, Fernando J. Duran§, Adriana S. Veleiro§, Gerardo Burton§ and Alexander Kasal*† 2119-2125 Full: PDF (332 K)

Dancing of the Second Aromatic Residue around the 6,8-Diazabicyclo[3.2.2]nonane Framework: Influence on σ Receptor Affinity and Cytotoxicity Ralph Holl†, Dirk Schepmann†, Roland Frohlich‡, Renate Grunert§, Patrick J. Bednarski§ and Bernhard Wunsch*† 2126-2137 Full: PDF (235 K)

Synthesis and in Vitro Characterization of Radioiodinatable Benzodiazepines Selective for Type 1 and Type 2 Cholecystokinin Receptors Eyup Akgun‡, Meike Korner†, Fan Gao†, Kaleeckal G. Harikumar†, Beatrice Waser§, Jean Claude Reubi*§, Philip S. Portoghese*‡ and Laurence J. Miller*† 2138-2147 Full: PDF (702 K)

Brief Articles

Discovery of 6-({4-[2-(4-tert-Butylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): An Orally Active Antagonist of the Gonadotropin Releasing Hormone Receptor (GnRH-R) Jeffrey C. Pelletier*†, Murty V. Chengalvala‡, Joshua E. Cottom‡, Irene B. Feingold§, Daniel M. Green†, Diane B. Hauze†, Christine A. Huselton§, James W. Jetter†, Gregory S. Kopf‡, Joseph T. Lundquist, †, Ronald L. Magolda†, Charles W. Mann†, John F. Mehlmann†, John F. Rogers†, Linda K. Shanno‡, William R. Adams§, Cesario O. Tio§ and Jay E. Wrobel† 2148-2152 Full: PDF (205 K)

Nε-Thioacetyl-Lysine-Containing Tri-, Tetra-, and Pentapeptides as SIRT1 and SIRT2 Inhibitors Paivi H. Kiviranta*†, Tiina Suuronen‡, Erik A. A. Wallen†§, Jukka Leppanen†, Jussi Tervonen†, Sergiy Kyrylenko‡#, Antero Salminen‡, Antti Poso† and Elina M. Jarho† 2153-2156 Full: PDF (101 K)

Novel Peptidomimetics Containing a Vinyl Ester Moiety as Highly Potent and Selective Falcipain-2 Inhibitors Roberta Ettari*†, Nicola Micale†, Tanja Schirmeister‡, Christoph Gelhaus§, Matthias Leippe§, Emanuela Nizi, Maria Emilia Di Francesco, Silvana Grasso† and Maria Zappal 2157-2160 Full: PDF (82 K)

Book Reviews

Book Review of Drug Truths. Dispelling the Myths About Pharma R&D Manfred E. Wolff 2161-2161 Full: PDF (34 K)

Book Review of Pathway Analysis for Drug Discovery. Computational Infrastructure and Applications Donald B. Boyd 2161-2162 Full: PDF (34 K)