Perspectives
| The pKBHX Database: Toward a Better Understanding of Hydrogen-Bond Basicity for Medicinal Chemists Christian Laurence, Ken A. Brameld, Jerome Graton, Jean-Yves Le Questel and Eric Renault 4073-4086  |
| Full: PDF (2172 K) |
Letters
| Virtual Screening Approach for the Identification of New Rac1 Inhibitors Nicola Ferri, Alberto Corsini, Paolo Bottino, Francesca Clerici and Alessandro Contini 4087-4090  |
| Full: PDF (2181 K) |
| Identification of an Orally Active Opioid Receptor-like 1 (ORL1) Receptor Antagonist 4-{3-[(2R)-2,3-Dihydroxypropyl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-[(1S,3S,4R)-spiro[bicyclo[2.2.1]heptane-2,1′-cyclopropan]-3-ylmethyl]piperidine as Clinical Candidate Atsushi Satoh, Takeshi Sagara, Hiroki Sakoh, Masaya Hashimoto, Hiroshi Nakashima, Tetsuya Kato, Yasuhiro Goto, Sayaka Mizutani, Tomoko Azuma-Kanoh, Takeshi Tani, Shoki Okuda, Osamu Okamoto, Satoshi Ozaki, Yoshikazu Iwasawa, Hisashi Ohta and Hiroshi Kawamoto 4091-4094  |
| Full: PDF (846 K) |
| Site-Activated Multifunctional Chelator with Acetylcholinesterase and Neuroprotective−Neurorestorative Moieties for Alzheimer’s Therapy Hailin Zheng, Moussa B. H. Youdim and Mati Fridkin 4095-4098  |
| Full: PDF (823 K) |
| Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase Koen Vandyck, Maxwell D. Cummings, Origene Nyanguile, Carlo W. Boutton, Sandrine Vendeville, David McGowan, Benoit Devogelaere, Katie Amssoms, Stefaan Last, Klara Rombauts, Abdellah Tahri, Pedro Lory, Lili Hu, Derek A. Beauchamp, Kenny Simmen and Pierre Raboisson 4099-4102  |
| Full: PDF (2162 K) |
| Discovery of Molecular Switches That Modulate Modes of Metabotropic Glutamate Receptor Subtype 5 (mGlu5) Pharmacology in Vitro and in Vivo within a Series of Functionalized, Regioisomeric 2- and 5-(Phenylethynyl)pyrimidines Sameer Sharma, Jeffrey Kedrowski, Jerri M. Rook, Randy L. Smith, Carrie K. Jones, Alice L. Rodriguez, P. Jeffrey Conn and Craig W. Lindsley 4103-4106  |
| Full: PDF (1112 K) |
| Trisulfonated Porphyrazines: New Photosensitizers for the Treatment of Retinal and Subretinal Edema Johan E. van Lier, Hongjian Tian, Hasrat Ali, Nicole Cauchon and Haroutioun M. Hassessian 4107-4110  |
| Full: PDF (919 K) |
| Synthesis and Biological Evaluation of a Novel 3-Sulfonyl-8-azabicyclo[3.2.1]octane Class of Long Chain Fatty Acid Elongase 6 (ELOVL6) Inhibitors Tsuyoshi Nagase, Toshiyuki Takahashi, Takahide Sasaki, Akira Nagumo, Ken Shimamura, Yasuhisa Miyamoto, Hidefumi Kitazawa, Maki Kanesaka, Ryo Yoshimoto, Katsumi Aragane, Shigeru Tokita and Nagaaki Sato 4111-4114  |
| Full: PDF (823 K) |
| Synthesis and Evaluation of a Series of Heterobiarylamides That Are Centrally Penetrant Metabotropic Glutamate Receptor 4 (mGluR4) Positive Allosteric Modulators (PAMs) Darren W. Engers, Colleen M. Niswender, C. David Weaver, Satyawan Jadhav, Usha N. Menon, Rocio Zamorano, P. Jeffrey Conn, Craig W. Lindsley and Corey R. Hopkins 4115-4118  |
| Full: PDF (818 K) |
Articles
| The Immobilization of Gossypol Derivative on N-Polyvinylpyrrolidone Increases its Water Solubility and Modifies Membrane-Active Properties Maksim Ionov, Nataliya Gordiyenko, Ewa Olchowik, Nina Baram, Khairulla Zijaev, Bakhtiyar Salakhutdinov, Maria Bryszewska and Maria Zamaraeva 4119-4125  |
| Full: PDF (834 K) |
| Octahydropyrrolo[3,4-c]pyrrole: A Diamine Scaffold for Construction of Either α4β2 or α7-Selective Nicotinic Acetylcholine Receptor (nAChR) Ligands. Substitutions that Switch Subtype Selectivity William H. Bunnelle, Karin R. Tietje, Jennifer M. Frost, Dan Peters, Jianguo Ji, Tao Li, Marc J. C. Scanio, Lei Shi, David J. Anderson, Tino Dyhring, Jens H. Grønlien, Hilde Ween, Kirsten Thorin-Hagene and Michael D. Meyer 4126-4141  |
| Full: PDF (1208 K) |
| The First Bioreversible Prodrug of Metformin with Improved Lipophilicity and Enhanced Intestinal Absorption Kristiina M. Huttunen, Anne Mannila, Krista Laine, Eeva Kemppainen, Jukka Leppanen, Jouko Vepsalainen, Tomi Jarvinen and Jarkko Rautio 4142-4148  |
| Full: PDF (776 K) |
| Na+ Currents in Cardioprotection: Better to Be Late Bruno Le Grand, Christophe Pignier, Robert Letienne, Francis Colpaert, Florence Cuisiat, Francoise Rolland, Agnes Mas, Maud Borras and Bernard Vacher 4149-4160  |
| Full: PDF (1114 K) |
| In Vitro Intrinsic Clearance-Based Optimization of N3-Phenylpyrazinones as Corticotropin-Releasing Factor-1 (CRF1) Receptor Antagonists Richard A. Hartz, Vijay T. Ahuja, Maria Rafalski, William D. Schmitz, Allison B. Brenner, Derek J. Denhart, Jonathan L. Ditta, Jeffrey A. Deskus, Eddy W. Yue, Argyrios G. Arvanitis, Snjezana Lelas, Yu-Wen Li, Thaddeus F. Molski, Harvey Wong, James E. Grace, Kimberley A. Lentz, Jianqing Li, Nicholas J. Lodge, Robert Zaczek, Andrew P. Combs, Richard E. Olson, Ronald J. Mattson, Joanne J. Bronson and John E. Macor 4161-4172  |
| Full: PDF (1065 K) |
| Synthesis, Structure−Activity Relationships, and In Vivo Evaluation of N3-Phenylpyrazinones as Novel Corticotropin-Releasing Factor-1 (CRF1) Receptor Antagonists Richard A. Hartz, Vijay T. Ahuja, Argyrios G. Arvanitis, Maria Rafalski, Eddy W. Yue, Derek J. Denhart, William D. Schmitz, Jonathan L. Ditta, Jeffrey A. Deskus, Allison B. Brenner, Frank W. Hobbs, Joseph Payne, Snjezana Lelas, Yu-Wen Li, Thaddeus F. Molski, Gail K. Mattson, Yong Peng, Harvey Wong, James E. Grace, Kimberley A. Lentz, Jingfang Qian-Cutrone, Xiaoliang Zhuo, Yue-Zhong Shu, Nicholas J. Lodge, Robert Zaczek, Andrew P. Combs, Richard E. Olson, Joanne J. Bronson, Ronald J. Mattson and John E. Macor 4173-4191  |
| Full: PDF (1274 K) |
| Design, Synthesis, Biological Evaluation, and Structure−Activity Relationship (SAR) Discussion of Dipeptidyl Boronate Proteasome Inhibitors, Part I: Comprehensive Understanding of the SAR of α-Amino Acid Boronates Yongqiang Zhu, Xin Zhao, Xinrong Zhu, Gang Wu, Yuejie Li, Yuheng Ma, Yunxia Yuan, Jie Yang, Yang Hu, Li Ai and Qingzhi Gao 4192-4199  |
| Full: PDF (1218 K) |
| Novel Lead Structures for p38 MAP Kinase via FieldScreen Virtual Screening Timothy J. Cheeseright, Melanie Holm, Frank Lehmann, Sabine Luik, Marcia Gottert, James L. Melville and Stefan Laufer 4200-4209  |
| Full: PDF (3791 K) |
| Discovery of Geranylgeranyltransferase-I Inhibitors with Novel Scaffolds by the Means of Quantitative Structure−Activity Relationship Modeling, Virtual Screening, and Experimental Validation Yuri K. Peterson, Xiang S. Wang, Patrick J. Casey and Alexander Tropsha 4210-4220  |
| Full: PDF (1778 K) |
| Generation of Ligand-Based Pharmacophore Model and Virtual Screening for Identification of Novel Tubulin Inhibitors with Potent Anticancer Activity Yi-Kun Chiang, Ching-Chuan Kuo, Yu-Shan Wu, Chung-Tong Chen, Mohane Selvaraj Coumar, Jian-Sung Wu, Hsing-Pang Hsieh, Chi-Yen Chang, Huan-Yi Jseng, Ming-Hsine Wu, Jiun-Shyang Leou, Jen-Shin Song, Jang-Yang Chang, Ping-Chiang Lyu, Yu-Sheng Chao and Su-Ying Wu 4221-4233  |
| Full: PDF (4562 K) |
| Structural Assessment and Biological Evaluation of Two N3S Bombesin Derivatives Eleni Gourni, Penelope Bouziotis, Dimitra Benaki, George Loudos, Stavros Xanthopoulos, Maria Paravatou-Petsotas, Maria Mavri-Vavagianni, Maria Pelecanou, Spyros C. Archimandritis and Alexandra D. Varvarigou 4234-4246  |
| Full: PDF (2761 K) |
| Inhibition of Influenza Virus Infections by Sialylgalactose-Binding Peptides Selected from a Phage Library Teruhiko Matsubara, Machiko Sumi, Hiroyuki Kubota, Takao Taki, Yoshio Okahata and Toshinori Sato 4247-4256  |
| Full: PDF (4446 K) |
| A Small-Molecule Inhibitor of Nipah Virus Envelope Protein-Mediated Membrane Fusion Sabine Niedermeier, Katrin Singethan, Sebastian G. Rohrer, Magnus Matz, Markus Kossner, Sandra Diederich, Andrea Maisner, Jens Schmitz, Georg Hiltensperger, Knut Baumann, Ulrike Holzgrabe and Jurgen Schneider-Schaulies 4257-4265  |
| Full: PDF (3396 K) |
| Side Chain Flexibilities in the Human Ether-a-go-go Related Gene Potassium Channel (hERG) Together with Matched-Pair Binding Studies Suggest a New Binding Mode for Channel Blockers Ulrich Zachariae, Fabrizio Giordanetto and Andrew G. Leach 4266-4276  |
| Full: PDF (7188 K) |
| Structure−Activity Relationships and Cancer-Cell Selective Toxicity of Novel Inhibitors of Glioma-Associated Oncogene Homologue 1 (Gli1) Mediated Transcription Neeraj Mahindroo, Michele C. Connelly, Chandanamali Punchihewa, Hiromichi Kimura, Matthew P. Smeltzer, Song Wu and Naoaki Fujii 4277-4287  |
| Full: PDF (1698 K) |
| Discovery of Novel 2-Aminobenzamide Inhibitors of Heat Shock Protein 90 as Potent, Selective and Orally Active Antitumor Agents Kenneth H. Huang, James M. Veal, R. Patrick Fadden, John W. Rice, Jeron Eaves, Jon-Paul Strachan, Amy F. Barabasz, Briana E. Foley, Thomas E. Barta, Wei Ma, Melanie A. Silinski, Mei Hu, Jeffrey M. Partridge, Anisa Scott, Laura G. DuBois, Tiffany Freed, Paul M. Steed, Andy J. Ommen, Emilie D. Smith, Philip F. Hughes, Angela R. Woodward, Gunnar J. Hanson, W. Stephen McCall, Christopher J. Markworth, Lindsay Hinkley, Matthew Jenks, Lifeng Geng, Meredith Lewis, James Otto, Bert Pronk, Katleen Verleysen and Steven E. Hall 4288-4305  |
| Full: PDF (1803 K) |
| Conjugation of 2-(1′-Hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to Carbohydrates Changes its Subcellular Distribution and Enhances Photodynamic Activity in Vivo Xiang Zheng, Janet Morgan, Suresh K. Pandey, Yihui Chen, Erin Tracy, Heinz Baumann, Joseph R. Missert, Carrie Batt, Jennifer Jackson, David A. Bellnier, Barbara W. Henderson and Ravindra K. Pandey 4306-4318  |
| Full: PDF (4238 K) |
| Is Glutathione the Major Cellular Target of Cisplatin? A Study of the Interactions of Cisplatin with Cancer Cell Extracts Yonit Kasherman, Stefan Sturup and Dan Gibson 4319-4328  |
| Full: PDF (1155 K) |
| Chemical and Biological Investigation of Cyclopropyl Containing Diaryl-pyrazole-3-carboxamides as Novel and Potent Cannabinoid Type 1 Receptor Antagonists Gyorgy Szabo, Balazs Varga, Dora Payer-Lengyel, Attila Szemzo, Peter Erdelyi, Krisztina Vukics, Judit Szikra, Eva Hegyi, Monika Vastag, Bela Kiss, Judit Laszy, Istvan Gyertyan and Janos Fischer 4329-4337  |
| Full: PDF (1430 K) |
| The Role of Amphiphilicity and Negative Charge in Glycoprotein 41 Interactions in the Hydrophobic Pocket Miriam Gochin and Lifeng Cai 4338-4344  |
| Full: PDF (1841 K) |
| Synthesis, Binding, and Modeling Studies of New Cytisine Derivatives, as Ligands for Neuronal Nicotinic Acetylcholine Receptor Subtypes Bruno Tasso, Caterina Canu Boido, Emanuela Terranova, Cecilia Gotti, Loredana Riganti, Francesco Clementi, Roberto Artali, Gabriella Bombieri, Fiorella Meneghetti and Fabio Sparatore 4345-4357  |
| Full: PDF (4544 K) |
| Potential Neuroprotective Drugs in Cerebral Ischemia: New Saturated and Polyunsaturated Lipids Coupled to Hydrophilic Moieties: Synthesis and Biological Activity Alain Cesar Biraboneye, Sebastien Madonna, Younes Laras, Slavica Krantic, Pamela Maher and Jean-Louis Kraus 4358-4369  |
| Full: PDF (2274 K) |
| Novel Small Molecule Bradykinin B2 Receptor Antagonists Christoph Gibson, Karsten Schnatbaum, Jochen R. Pfeifer, Elsa Locardi, Matthias Paschke, Ulf Reimer, Uwe Richter, Dirk Scharn, Alexander Faussner and Thomas Tradler 4370-4379  |
| Full: PDF (1430 K) |
| Cell Division Cycle 7 Kinase Inhibitors: 1H-Pyrrolo[2,3-b]pyridines, Synthesis and Structure−Activity Relationships Antonella Ermoli, Alberto Bargiotti, Maria Gabriella Brasca, Antonella Ciavolella, Nicoletta Colombo, Gabriele Fachin, Antonella Isacchi, Maria Menichincheri, Antonio Molinari, Alessia Montagnoli, Antonio Pillan, Sonia Rainoldi, Federico Riccardi Sirtori, Francesco Sola, Sandrine Thieffine, Marcellino Tibolla, Barbara Valsasina, Daniele Volpi, Corrado Santocanale and Ermes Vanotti 4380-4390  |
| Full: PDF (1697 K) |
| Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase by Acyclic Nucleoside Phosphonates: A New Class of Antimalarial Therapeutics Dianne T. Keough, Dana Hockova, Antonin Holy, Lieve M. J. Naesens, Tina S. Skinner-Adams, John de Jersey and Luke W. Guddat 4391-4399  |
| Full: PDF (3240 K) |
| Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926) Martin R. Tremblay, Andre Lescarbeau, Michael J. Grogan, Eddy Tan, Grace Lin, Brian C. Austad, Lin-Chen Yu, Mark L. Behnke, Somarajan J. Nair, Margit Hagel, Kerry White, James Conley, Joseph D. Manna, Teresa M. Alvarez-Diez, Jennifer Hoyt, Caroline N. Woodward, Jens R. Sydor, Melissa Pink, John MacDougall, Matthew J. Campbell, Jill Cushing, Jeanne Ferguson, Michael S. Curtis, Karen McGovern, Margaret A. Read, Vito J. Palombella, Julian Adams and Alfredo C. Castro 4400-4418  |
| Full: PDF (2805 K) |
| Identification of Peptide Substrate and Small Molecule Inhibitors of Testis-Specific Serine/Threonine Kinase1 (TSSK1) By the Developed Assays Leilei Zhang, Yu Yan, Zijie Liu, Zeper Abliz and Gang Liu 4419-4428  |
| Full: PDF (1292 K) |
| Definition of the G Protein-Coupled Receptor Transmembrane Bundle Binding Pocket and Calculation of Receptor Similarities for Drug Design David E. Gloriam, Steven M. Foord, Frank E. Blaney and Stephen L. Garland 4429-4442  |
| Full: PDF (5921 K) |
| Discovery of a Peroxisome Proliferator Activated Receptor γ (PPARγ) Modulator with Balanced PPARα Activity for the Treatment of Type 2 Diabetes and Dyslipidemia Weiguo Liu, Kun Liu, Harold B. Wood, Margaret E. McCann, Thomas W. Doebber, Ching H. Chang, Taro E. Akiyama, Monica Einstein, Joel P. Berger and Peter T. Meinke 4443-4453  |
| Full: PDF (1045 K) |
| One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening Chidochangu P. Mpamhanga, Daniel Spinks, Lindsay B. Tulloch, Emma J. Shanks, David A. Robinson, Iain T. Collie, Alan H. Fairlamb, Paul G. Wyatt, Julie A. Frearson, William N. Hunter, Ian H. Gilbert and Ruth Brenk 4454-4465  |
| Full: PDF (3781 K) |
| Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120) Gerald J. Roth, Armin Heckel, Florian Colbatzky, Sandra Handschuh, Jorg Kley, Thorsten Lehmann-Lintz, Ralf Lotz, Ulrike Tontsch-Grunt, Rainer Walter and Frank Hilberg 4466-4480  |
| Full: PDF (1874 K) |
| Heterobiaryl Human Immunodeficiency Virus Entry Inhibitors Rong-Jian Lu, John A. Tucker, Jason Pickens, You-An Ma, Tatiana Zinevitch, Olga Kirichenko, Vitalii Konoplev, Svetlana Kuznetsova, Sergey Sviridov, Enugurthi Brahmachary, Alisher Khasanov, Charles Mikel, Yang Yang, Changhui Liu, Jian Wang, Stephanie Freel, Shelly Fisher, Alana Sullivan, Jiying Zhou, Sherry Stanfield-Oakley, Brian Baker, Jeff Sailstad, Michael Greenberg, Dani Bolognesi, Brian Bray, Barney Koszalka, Peter Jeffs, Cynthia Jeffries, Alexander Chucholowski and Connie Sexton 4481-4487  |
| Full: PDF (1133 K) |
| In Silico Prediction of Volume of Distribution in Human Using Linear and Nonlinear Models on a 669 Compound Data Set Giuliano Berellini, Clayton Springer, Nigel J. Waters and Franco Lombardo 4488-4495  |
| Full: PDF (2065 K) |
| Discovery of 2-[5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-1H-pyrazol-3-yl]-1,5,5-trimethyl-1,5-dihydro-imidazol-4-thione (BPR-890) via an Active Metabolite. A Novel, Potent and Selective Cannabinoid-1 Receptor Inverse Agonist with High Antiobesity Efficacy in DIO Mice Chien-Huang Wu, Ming-Shiu Hung, Jen-Shin Song, Teng-Kuang Yeh, Ming-Chen Chou, Cheng-Ming Chu, Jiing-Jyh Jan, Min-Tsang Hsieh, Shi-Liang Tseng, Chun-Ping Chang, Wan-Ping Hsieh, Yinchiu Lin, Yen-Nan Yeh, Wan-Ling Chung, Chun-Wei Kuo, Chin-Yu Lin, Horng-Shing Shy, Yu-Sheng Chao and Kak-Shan Shia 4496-4510  |
| Full: PDF (2146 K) |
| Apogossypol Derivatives as Pan-Active Inhibitors of Antiapoptotic B-Cell Lymphoma/Leukemia-2 (Bcl-2) Family Proteins Jun Wei, Shinichi Kitada, Michele F. Rega, John L. Stebbins, Dayong Zhai, Jason Cellitti, Hongbin Yuan, Aras Emdadi, Russell Dahl, Ziming Zhang, Li Yang, John C. Reed and Maurizio Pellecchia 4511-4523  |
| Full: PDF (3508 K) |
| Synthesis and Preclinical Evaluation of Novel PET Probes for P-Glycoprotein Function and Expression Aren van Waarde, Nisha K. Ramakrishnan, Anna A. Rybczynska, Philip H. Elsinga, Francesco Berardi, Johan R. de Jong, Chantal Kwizera, Roberto Perrone, Mariangela Cantore, Jurgen W. A. Sijbesma, Rudi A. Dierckx and Nicola A. Colabufo 4524-4532  |
| Full: PDF (2318 K) |
Brief Articles
| L337H Mutant of Rat Neuronal Nitric Oxide Synthase Resembles Human Neuronal Nitric Oxide Synthase toward Inhibitors Jianguo Fang, Haitao Ji, Graham R. Lawton, Fengtian Xue, Linda J. Roman and Richard B. Silverman 4533-4537  |
| Full: PDF (1315 K) |
| Isocombretastatins A versus Combretastatins A: The Forgotten isoCA-4 Isomer as a Highly Promising Cytotoxic and Antitubulin Agent Samir Messaoudi, Bret Treguier, Abdallah Hamze, Olivier Provot, Jean-Francois Peyrat, Jordi Rodrigo De Losada, Jian-Miao Liu, Jerome Bignon, Joanna Wdzieczak-Bakala, Sylviane Thoret, Joelle Dubois, Jean-Daniel Brion and Mouad Alami 4538-4542  |
| Full: PDF (2840 K) |
| Allosteric Modulators of the Adenosine A1 Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3-benzoylthiophenes Luigi Aurelio, Celine Valant, Bernard L. Flynn, Patrick M. Sexton, Arthur Christopoulos and Peter J. Scammells 4543-4547  |
| Full: PDF (864 K) |
Book Reviews
| Theilheimer’s Synthetic Methods of Organic Chemistry. Volume 73 Jonathan L. Vennerstrom 4548-4548 |
| Full: PDF (558 K) |
| Book Review of The Cannabinoid Receptors Kennerly S. Patrick 4548-4548 |
| Full: PDF (558 K) |
Additions and Corrections
| Corrections to Rational Modification of a Candidate Cancer Drug for Use against Chagas Disease James M. Kraus, Christophe L. M. J. Verlinde, Mandana Karimi, Galina I. Lepesheva, Michael H. Gelb and Frederick S. Buckner 4549-4549 |
| Full: PDF (543 K) |
| Corrections to Large-Scale Application of High-Throughput Molecular Mechanics with Poisson−Boltzmann Surface Area for Routine Physics-Based Scoring of Protein−Ligand Complexes Scott P. Brown and Steven W. Muchmore 4549-4549 |
| Full: PDF (543 K) |