PERSPECTIVE
| Target Flexibility: An Emerging Consideration in Drug Discovery and Design Pietro Cozzini, Glen E. Kellogg, Francesca Spyrakis, Donald J. Abraham, Gabriele Costantino, Andrew Emerson, Francesca Fanelli, Holger Gohlke, Leslie A. Kuhn, Garrett M. Morris, Modesto Orozco, Thelma A. Pertinhez, Menico Rizzi, and Christoph A. Sotriffer 6237-6255 |
| Full: PDF (2447 K) |
LETTERS
| Ni(II), Cu(II), and Zn(II) Diethyldithiocarbamate Complexes Show Various Activities Against the Proteasome in Breast Cancer Cells Boris Cvek, Vesna Milacic, Jan Taraba, and Q. Ping Dou 6256-6258  |
| Full: PDF (288 K) |
| Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of β-Secretase James C. Barrow, Shaun R. Stauffer, Kenneth E. Rittle, Phung L. Ngo, ZhiQiang Yang, Harold G. Selnick, Samuel L. Graham, Sanjeev Munshi, Georgia B. McGaughey, M. Katharine Holloway, Adam J. Simon, Eric A. Price, Sethu Sankaranarayanan, Dennis Colussi, Katherine Tugusheva, Ming-Tain Lai, Amy S. Espeseth, Min Xu, Qian Huang, Abigail Wolfe, Beth Pietrak, Paul Zuck, Dorothy A. Levorse, Daria Hazuda, and Joseph P. Vacca 6259-6262  |
| Full: PDF (379 K) |
ARTICLES
| A Copper(I)-Catalyzed 1,2,3-Triazole Azide−Alkyne Click Compound Is a Potent Inhibitor of a Multidrug-Resistant HIV-1 Protease Variant Michael J. Giffin, Holly Heaslet, Ashraf Brik, Ying-Chuan Lin, Gabrielle Cauvi, Chi-Huey Wong, Duncan E. McRee, John H. Elder, C. David Stout, and Bruce E. Torbett 6263-6270  |
| Full: PDF (947 K) |
| Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold Brad Herberich, Guo-Qiang Cao, Partha P. Chakrabarti, James R. Falsey, Liping Pettus, Robert M. Rzasa, Anthony B. Reed, Andreas Reichelt, Kelvin Sham, Maya Thaman, Ryan P. Wurz, Shimin Xu, Dawei Zhang, Faye Hsieh, Matthew R. Lee, Rashid Syed, Vivian Li, David Grosfeld, Matthew H. Plant, Bradley Henkle, Lisa Sherman, Scot Middleton, Lu Min Wong, and Andrew S. Tasker 6271-6279  |
| Full: PDF (690 K) |
| 3-Amino-7-phthalazinylbenzoisoxazoles as a Novel Class of Potent, Selective, and Orally Available Inhibitors of p38α Mitogen-Activated Protein Kinase Liping H. Pettus, Shimin Xu, Guo-Qiang Cao, Partha P. Chakrabarti, Robert M. Rzasa, Kelvin Sham, Ryan P. Wurz, Dawei Zhang, Scott Middleton, Bradley Henkle, Matthew H. Plant, Christiaan J. M. Saris, Lisa Sherman, Lu Min Wong, David A. Powers, Yanyan Tudor, Violeta Yu, Matthew R. Lee, Rashid Syed, Faye Hsieh, and Andrew S. Tasker 6280-6292  |
| Full: PDF (685 K) |
| Modeling Binding Modes of α7 Nicotinic Acetylcholine Receptor with Ligands: The Roles of Gln117 and Other Residues of the Receptor in Agonist Binding Xiaoqin Huang, Fang Zheng, Clare Stokes, Roger L. Papke, and Chang-Guo Zhan 6293-6302  |
| Full: PDF (2622 K) |
| Discovery of Novel PPAR Ligands by a Virtual Screening Approach Based on Pharmacophore Modeling, 3D Shape, and Electrostatic Similarity Screening Patrick Markt, Rasmus K. Petersen, Esben N. Flindt, Karsten Kristiansen, Johannes Kirchmair, Gudrun Spitzer, Simona Distinto, Daniela Schuster, Gerhard Wolber, Christian Laggner, and Thierry Langer 6303-6317  |
| Full: PDF (4640 K) |
| Design, Synthesis, and Biological Evaluation of Novel Constrained meta-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor α and γ Dual Agonists Young-Ger Suh, Nam-Jung Kim, Bon-Woong Koo, Kwang-Ok Lee, Sung-Hyun Moon, Dong-Hyung Shin, Jong-Wha Jung, Seung-Mann Paek, Dong-Jo Chang, Funan Li, Hyun-Jin Kang, Tuong Vy Thi Le, Yu Na Chae, Chang Yell Shin, Mi-Kyung Kim, Joong In Lim, Jae-Sang Ryu, and Hyun-Ju Park 6318-6333  |
| Full: PDF (787 K) |
| The Importance of Micelle-Bound States for the Bioactivities of Bifunctional Peptide Derivatives for δ/μ Opioid Receptor Agonists and Neurokinin 1 Receptor Antagonists Takashi Yamamoto, Padma Nair, Neil E. Jacobsen, Peg Davis, Shou-wu Ma, Edita Navratilova, Sharif Moye, Josephine Lai, Henry I. Yamamura, Todd W. Vanderah, Frank Porreca, and Victor J. Hruby 6334-6347  |
| Full: PDF (843 K) |
| Toward Optimization of the Linker Substructure Common to Transthyretin Amyloidogenesis Inhibitors Using Biochemical and Structural Studies Steven M. Johnson, Stephen Connelly, Ian A. Wilson, and Jeffery W. Kelly 6348-6358  |
| Full: PDF (2394 K) |
| Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 9. From 1,4-Benzodioxane to 1,4-Dioxane Ring as a Promising Template of Novel α1D-Adrenoreceptor Antagonists, 5-HT1A Full Agonists, and Cytotoxic Agents Wilma Quaglia, Alessandro Piergentili, Fabio Del Bello, Yogita Farande, Mario Giannella, Maria Pigini, Giovanni Rafaiani, Antonio Carrieri, Consuelo Amantini, Roberta Lucciarini, Giorgio Santoni, Elena Poggesi, and Amedeo Leonardi 6359-6370  |
| Full: PDF (479 K) |
| Synthesis and Utilization of Chiral α-Methylated α-Amino Acids with a Carboxyalkyl Side Chain in the Design of Novel Grb2-SH2 Peptide Inhibitors Free of Phosphotyrosine Ya-Qiu Long, Ting Xue, Yan-Li Song, Zu-Long Liu, Shao-Xu Huang, and Qiang Yu 6371-6380  |
| Full: PDF (649 K) |
| 5-N-Methylated Quindoline Derivatives as Telomeric G-Quadruplex Stabilizing Ligands: Effects of 5-N Positive Charge on Quadruplex Binding Affinity and Cell Proliferation Yu-Jing Lu, Tian-Miao Ou, Jia-Heng Tan, Jin-Qiang Hou, Wei-Yan Shao, Dan Peng, Ning Sun, Xiao-Dong Wang, Wei-Bin Wu, Xian-Zhang Bu, Zhi-Shu Huang, Dik-Lung Ma, Kwok-Yin Wong, and Lian-Quan Gu 6381-6392  |
| Full: PDF (1010 K) |
| Bornyl- and Isobornyl-Δ8-tetrahydrocannabinols: A Novel Class of Cannabinergic Ligands Dai Lu, Jianxin Guo, Richard I. Duclos Jr., Anna L. Bowman, and Alexandros Makriyannis 6393-6399  |
| Full: PDF (536 K) |
| Isosorbide-2-carbamate Esters: Potent and Selective Butyrylcholinesterase Inhibitors Ciaran G. Carolan, Gerald P. Dillon, Joanne M. Gaynor, Sean Reidy, Sheila A. Ryder, Denise Khan, Juan F. Marquez, and John F. Gilmer 6400-6409  |
| Full: PDF (690 K) |
| Identification of a Nonbasic, Nitrile-Containing Cathepsin K Inhibitor (MK-1256) that is Efficacious in a Monkey Model of Osteoporosis Jöel Robichaud, W. Cameron Black, Michel Thérien, Julie Paquet, Renata M. Oballa, Christopher I. Bayly, Daniel J. McKay, Qingping Wang, Elise Isabel, Serge Léger, Christophe Mellon, Donald B. Kimmel, Gregg Wesolowski, M. David Percival, Fréderic Massé, Sylvie Desmarais, Jean-Pierre Falgueyret, and Sheldon N. Crane 6410-6420  |
| Full: PDF (510 K) |
| Soluble 3′,6-Substituted Indirubins with Enhanced Selectivity toward Glycogen Synthase Kinase -3 Alter Circadian Period Konstantina Vougogiannopoulou, Yoan Ferandin, Karima Bettayeb, Vassilios Myrianthopoulos, Olivier Lozach, Yunzhen Fan, Carl Hirschie Johnson, Prokopios Magiatis, Alexios-Leandros Skaltsounis, Emmanuel Mikros, and Laurent Meijer 6421-6431  |
| Full: PDF (1671 K) |
| Differences between High- and Low-Affinity Complexes of Enzymes and Nonenzymes Heather A. Carlson, Richard D. Smith, Nickolay A. Khazanov, Paul D. Kirchhoff, James B. Dunbar Jr., and Mark L. Benson 6432-6441  |
| Full: PDF (3013 K) |
| Conjugated Chitosan as a Novel Platform for Oral Delivery of Paclitaxel Eunhye Lee, Jinju Lee, In-Hyun Lee, Mikyung Yu, Hyungjun Kim, Su Young Chae, and Sangyong Jon 6442-6449  |
| Full: PDF (1442 K) |
| Modified Peptides as Potent Inhibitors of the Postsynaptic Density-95/N-Methyl-D-Aspartate Receptor Interaction Anders Bach, Celestine N. Chi, Thomas B. Olsen, Søren W. Pedersen, Martin U. Røder, Gar F. Pang, Rasmus P. Clausen, Per Jemth, and Kristian Strømgaard 6450-6459  |
| Full: PDF (1345 K) |
| α,β-Methylene-2′-deoxynucleoside 5′-Triphosphates as Noncleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2′-Deoxycyclonucleosides, 3,5′-Cyclo-dG, and 2,5′-Cyclo-dT Fengting Liang, Nidhi Jain, Troy Hutchens, David D. Shock, William A. Beard, Samuel H. Wilson, M. Paul Chiarelli, and Bongsup P. Cho 6460-6470  |
| Full: PDF (1344 K) |
| Discovery of 1,4-Substituted Piperidines as Potent and Selective Inhibitors of T-Type Calcium Channels Zhi-Qiang Yang, James C. Barrow, William D. Shipe, Kelly-Ann S. Schlegel, Youheng Shu, F. Vivien Yang, Craig W. Lindsley, Kenneth E. Rittle, Mark G. Bock, George D. Hartman, Victor N. Uebele, Cindy E. Nuss, Steve V. Fox, Richard L. Kraus, Scott M. Doran, Thomas M. Connolly, Cuyue Tang, Jeanine E. Ballard, Yuhsin Kuo, Emily D. Adarayan, Thomayant Prueksaritanont, Matthew M. Zrada, Michael J. Marino, Valerie Kuzmick Graufelds, Anthony G. DiLella, Ian J. Reynolds, Hugo M. Vargas, Patricia B. Bunting, Richard F. Woltmann, Michael M. Magee, Kenneth S. Koblan, and John J. Renger 6471-6477  |
| Full: PDF (500 K) |
| Combining Ligand-Based Pharmacophore Modeling, Quantitative Structure−Activity Relationship Analysis and in Silico Screening for the Discovery of New Potent Hormone Sensitive Lipase Inhibitors Mutasem O. Taha, Lina A. Dahabiyeh, Yasser Bustanji, Hiba Zalloum, and Suhair Saleh 6478-6494  |
| Full: PDF (879 K) |
| Gedunin, a Novel Hsp90 Inhibitor: Semisynthesis of Derivatives and Preliminary Structure−Activity Relationships Gary E. L. Brandt, Matthew D. Schmidt, Thomas E. Prisinzano, and Brian S. J. Blagg 6495-6502  |
| Full: PDF (302 K) |
| Discovery of 3-{5-[(6-Amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2-chlorophenoxy}-5-chlorobenzonitrile (MK-4965): A Potent, Orally Bioavailable HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor with Improved Potency against Key Mutant Viruses Thomas J. Tucker, John T. Sisko, Robert M. Tynebor, Theresa M. Williams, Peter J. Felock, Jessica A. Flynn, Ming-Tain Lai, Yuexia Liang, Georgia McGaughey, Meiquing Liu, Mike Miller, Gregory Moyer, Vandna Munshi, Rebecca Perlow-Poehnelt, Sridhar Prasad, John C. Reid, Rosa Sanchez, Maricel Torrent, Joseph P. Vacca, Bang-Lin Wan, and Youwei Yan 6503-6511  |
| Full: PDF (604 K) |
| Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding Alexander A. Parent, Jillian R. Gunther, and John A. Katzenellenbogen 6512-6530  |
| Full: PDF (777 K) |
| Thiophene Bioisosteres of Spirocyclic σ Receptor Ligands. 1. N-Substituted Spiro[piperidine-4,4′-thieno[3,2-c]pyrans] Christoph Oberdorf, Dirk Schepmann, Jose Miguel Vela, Jose Luis Diaz, Jörg Holenz, and Bernhard Wünsch 6531-6537  |
| Full: PDF (308 K) |
| Discovery of Bioavailable 4,4-Disubstituted Piperidines as Potent Ligands of the Chemokine Receptor 5 and Inhibitors of the Human Immunodeficiency Virus-1 Wieslaw M. Kazmierski, Christopher Aquino, Brian A. Chauder, Felix Deanda, Robert Ferris, Deborah K. Jones-Hertzog, Terrence Kenakin, Cecilia S. Koble, Christian Watson, Pat Wheelan, Hanbiao Yang, and Michael Youngman 6538-6546  |
| Full: PDF (292 K) |
| Rotationally Constrained 2,4-Diamino-5,6-disubstituted Pyrimidines: A New Class of Histamine H4 Receptor Antagonists with Improved Druglikeness and in Vivo Efficacy in Pain and Inflammation Models Marlon D. Cowart, Robert J. Altenbach, Huaqing Liu, Gin C. Hsieh, Irene Drizin, Ivan Milicic, Thomas R. Miller, David G. Witte, Neil Wishart, Shannon R. Fix-Stenzel, Michael J. McPherson, Ronald M. Adair, Jill M. Wetter, Brian M. Bettencourt, Kennan C. Marsh, James P. Sullivan, Prisca Honore, Timothy A. Esbenshade, and Jorge D. Brioni 6547-6557  |
| Full: PDF (175 K) |
| Synthesis and Structure−Activity Relationship Studies of Highly Potent Novel Oxazolidinone Antibacterials Takashi Komine, Akihiko Kojima, Yoshikazu Asahina, Tatsuhiro Saito, Hisashi Takano, Taku Shibue, and Yasumichi Fukuda 6558-6562  |
| Full: PDF (128 K) |
| Identification of Non-Nucleoside DNA Synthesis Inhibitors of Vaccinia Virus by High-Throughput Screening Mihai Ciustea, Janice Elaine Y. Silverman, Abigail M. Druck Shudofsky, and Robert P. Ricciardi 6563-6570  |
| Full: PDF (243 K) |
| Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H4 Receptor Ligands Robert J. Altenbach, Ronald M. Adair, Brian M. Bettencourt, Lawrence A. Black, Shannon R. Fix-Stenzel, Sujatha M. Gopalakrishnan, Gin C. Hsieh, Huaqing Liu, Kennan C. Marsh, Michael J. McPherson, Ivan Milicic, Thomas R. Miller, Timothy A. Vortherms, Usha Warrior, Jill M. Wetter, Neil Wishart, David G. Witte, Prisca Honore, Timothy A. Esbenshade, Arthur A. Hancock, Jorge D. Brioni, and Marlon D. Cowart 6571-6580  |
| Full: PDF (255 K) |
| 4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1 Keith A. Menear, Claire Adcock, Robert Boulter, Xiao-ling Cockcroft, Louise Copsey, Aaron Cranston, Krystyna J. Dillon, Jan Drzewiecki, Sheila Garman, Sylvie Gomez, Hashim Javaid, Frank Kerrigan, Charlotte Knights, Alan Lau, Vincent M. Loh Jr., Ian T. W. Matthews, Stephen Moore, Mark J. O’Connor, Graeme C. M. Smith, and Niall M. B. Martin 6581-6591  |
| Full: PDF (173 K) |
| Intracellular Trapping of cycloSal-Pronucleotides: Modification of Prodrugs with Amino Acid Esters Henning J. Jessen, Jan Balzarini, and Chris Meier 6592-6598  |
| Full: PDF (152 K) |
BRIEF ARTICLES
| Solution Kinetics Measurements Suggest HIV-1 Protease Has Two Binding Sites for Darunavir and Amprenavir Andrey Y. Kovalevsky, Arun K. Ghosh, and Irene T. Weber 6599-6603  |
| Full: PDF (657 K) |
| Synthesis and Evaluation of Novel Boron-Containing Complexes of Potential Use for the Selective Treatment of Malignant Melanoma Josep Bonjoch, Michael G. B. Drew, Asensio González, Francesca Greco, Samaila Jawaid, Helen M. I. Osborn, Nana Aba O. Williams, and Parveen Yaqoob 6604-6608  |
| Full: PDF (971 K) |
| Structure−Activity Relationships of Truncated D- and L-4′-Thioadenosine Derivatives as Species-Independent A3 Adenosine Receptor Antagonists Lak Shin Jeong, Shantanu Pal, Seung Ah Choe, Won Jun Choi, Kenneth A. Jacobson, Zhan-Guo Gao, Athena M. Klutz, Xiyan Hou, Hea Ok Kim, Hyuk Woo Lee, Sang Kook Lee, Dilip K. Tosh, and Hyung Ryong Moon 6609-6613  |
| Full: PDF (116 K) |
| 1H-Cyclopentapyrimidine-2,4(1H,3H)-dione-Related Ionotropic Glutamate Receptors Ligands. Structure−Activity Relationships and Identification of Potent and Selective iGluR5 Modulators Stefania Butini, Darryl S. Pickering, Elena Morelli, Salvatore Sanna Coccone, Francesco Trotta, Meri De Angelis, Egeria Guarino, Isabella Fiorini, Giuseppe Campiani, Ettore Novellino, Arne Schousboe, Jeppe K. Christensen, and Sandra Gemma 6614-6618  |
| Full: PDF (108 K) |
BOOK REVIEWS
| Book Review of Drug-like Properties: Concepts, Structure Design, and Methods Thomas E. Prisinzano 6619-6619 |
| Full: PDF (29 K) |
| Book Review of Bioconjugate Techniques. Second Edition Jane Guo Shiah 6619-6619 |
| Full: PDF (29 K) |
ADDITIONS AND CORRECTIONS
| Efficient Synthesis and Neuroprotective Effect of Substituted 1,3-Diphenyl-2-propen-1-ones Jae-Chul Jung, Soyong Jang, Yongnam Lee, Dongguk Min, Eunyoung Lim, Heyin Jung, Miyeon Oh, Seikwan Oh, and Mankil Jung 6620-6620 |
| Full: PDF (53 K) |
| Selective Structure-Based Virtual Screening for Full and Partial Agonists of the β2 Adrenergic Receptor Chris de Graaf and Didier Rognan 6620-6620 |
| Full: PDF (53 K) |