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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`August 12, 2004
`ACS Publications
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`Volume 47, Issue 17
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`Pages 4111-4338
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`Ribbon rendered illustration of the nuclear receptor heterodimer RXRα(cyan):PPARRγ (red) ligand binding domains
`bound with coactivator peptides (magenta) and agonist ligands (space- lling atoms where green is carbon, red is
`oxygen, and blue is nitrogen) (Haffner, C. D.; et al. J. Med. Chem. 2004, 47, 2010-2029).
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`In this issue:
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`Miniperspectives:Advances in Type 2 Diabetes
`Letters
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`Brief Articles
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`MINIPERSPECTIVES:ADVANCES IN TYPE 2 DIABETES
`
`Novel “Second-Generation” Approaches for the Control of Type 2 Diabetes
`
`David P. Rotella
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4111-4112 (Perspective)
`Publication Date (Web): July 20, 2004
`
` First Page
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` Full text
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Clinical
`On&at
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`Genetic
`Pred isposit ion Autoimmunity
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`Metabolic
`Defect
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`Gl1.1co:;e
`Impairment
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`Total
`
`Dia.hems l
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`- - - - - - - - - - - Time - - - - - - - - - - - - - -
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`Diabetes Mellitus: Pathogenesis and Treatment Strategies
`
`Jay S. Skyler
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`Journal of Medicinal Chemistry 2004, 47, 17, 4113-4117 (Perspective)
`Publication Date (Web): July 20, 2004
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` First Page
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` Full text
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`hPPARa
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`hPPARo N
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`Ligand -----+
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`-2
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`C
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`LBD
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`68%
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`70%
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`https://pubs.acs.org/toc/jmcmar/47/17
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`Peroxisome Proliferator-Activated Receptor α/γ Dual Agonists for the
`Treatment of Type 2 Diabetes
`ACS Publications
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`Brad R. Henke
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`Journal of Medicinal Chemistry 2004, 47, 17, 4118-4127 (Perspective)
`Publication Date (Web): July 20, 2004
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`
`lalCtilll!~·
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`~ •~1 r'°-im-Phe-n,,..se,,~p '-\.OI\I-S@r•L~M.,...~\I-Glt~.q,i",Arg-~llt-Glll<"'-rrp- oo-\,y$-~l;;lf-O~ -$1<~(cid:173)
`
`"'H',!><'fi,,.~
`
`Glucagon-like Peptide-1: The Basis of a New Class of Treatment for Type 2
`Diabetes
`
`Lotte Bjerre Knudsen
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4128-4134 (Perspective)
`Publication Date (Web): July 20, 2004
`
` First Page
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` Full text
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`-
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`Y :G .. o;,
`~mptying
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`! r /
`!~! ~
`
`Other potential
`substrates
`(e.g. GIP, GLP-2,
`PACAP)
`
`Active GLP-1
`
`i Glucose-dependent
`insulin biosynthesis
`and secretion
`J. Glucagon
`Improved (I-cell function
`
`Dipeptidyl Peptidase IV Inhibitors for the Treatment of Diabetes
`https://pubs.acs.org/toc/jmcmar/47/17
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`5/19
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`Inactive GLP-1
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`J. Food intake
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`Ann E. Weber
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Journal of Medicinal Chemistry 2004, 47, 17, 4135-4141 (Perspective)
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`(nucleus)
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`Prospects for Inhibitors of Protein Tyrosine Phosphatase 1B as Antidiabetic
`Drugs
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`Rob Hooft van Huijsduijnen, Wolfgang H. B. Sauer, Agnes Bombrun, and Dominique Swinnen
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4142-4146 (Perspective)
`Publication Date (Web): July 20, 2004
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`LETTERS
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Smac AVPI Peptide
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`Smac Mimetic 12d
`Structure-Based Design, Synthesis, and Evaluation of Conformationally
`Constrained Mimetics of the Second Mitochondria-Derived Activator of
`Caspase That Target the X-Linked Inhibitor of Apoptosis Protein/Caspase-9
`Interaction Site
`
`Haiying Sun, Zaneta Nikolovska-Coleska, Chao-Yie Yang, Liang Xu, York Tomita, Krzysztof Krajewski, Peter P. Roller
`, and Shaomeng Wang
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4147-4150 (Letter)
`Publication Date (Web): July 16, 2004
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` Abstract
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` Full text
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` ABSTRACT
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`S
`
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`
`I
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`Seed Cl Q,
`
`Lead Generation
`
`Fuji~.awa
`Library
`
`N
`
`F
`
`Rational Approaches to Discovery of Orally Active and Brain-Penetrable
`Quinazolinone Inhibitors of Poly(ADP-ribose)polymerase
`
`Kouji Hattori, Yoshiyuki Kido, Hirofumi Yamamoto, Junya Ishida, Kazunori Kamijo, Kenji Murano, Mitsuru Ohkubo,
`Takayoshi Kinoshita, Akinori Iwashita, Kayoko Mihara, Syunji Yamazaki, Nobuya Matsuoka, Yoshinori Teramura
`, and Hiroshi Miyake
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4151-4154 (Letter)
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`https://pubs.acs.org/toc/jmcmar/47/17
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`7/19
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`eed .-m: rag C( NH u ° C( NIH
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`RO
`
`O..._ . ~ ,....R1
`--.......,.....
`·~IN
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`2
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`H/OH
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`1
`Dopamine/Serotonin Receptor Ligands. 9. Oxygen-Containing Midsized
`Heterocyclic Ring Systems and Nonrigidized Analogues. A Step toward
`Dopamine D Receptor Selectivity
`5
`
`Thomas W. Wittig, Michael Decker, and Jochen Lehmann
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4155-4158 (Letter)
`Publication Date (Web): July 16, 2004
`
` Abstract
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` Full text
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`Bulky Nonproteinogenic Amino Acids Permit the Design of Very Small and
`Effective Cationic Antibacterial Peptides
`
`Bengt Erik Haug, Wenche Stensen, Trine Stiberg, and John S. Svendsen
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4159-4162 (Letter)
`Publication Date (Web): July 16, 2004
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` Abstract
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`Trp23
`H
`
`6. 15 A
`
`H
`
`CHI
`-
`3
`
`A Nonpeptidic Sulfonamide Inhibits the p53−mdm2 Interaction and Activates
`p53-Dependent Transcription in mdm2-Overexpressing Cells
`
`Peter S. Galatin and Donald J. Abraham
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`Journal of Medicinal Chemistry 2004, 47, 17, 4163-4165 (Letter)
`Publication Date (Web): July 21, 2004
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` Abstract
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` Full text
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`ARTICLES
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`
`
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`Human Integrin αvβ5: Homology Modeling and Ligand Binding
`
`Luciana Marinelli, Kay-E. Gottschalk, Axel Meyer, Ettore Novellino, and Horst Kessler
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4166-4177 (Article)
`Publication Date (Web): July 10, 2004
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` Abstract
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`c&en I WEBINARS
`Measuring Heavy Metals in Baby Fo,od
`Usiing1 ICP .. M S
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`t'narmacopnore
`determinaUon
`Flexible ligands
`
`uocKmg o,me
`pharmacophore
`
`
`
`
`r-ecep5 O ,
`⇒ H3~~ co c e
`water O O g O o 0
`Or"ented 1rigid dock 1ing1
`MID simulation
`Virtua I Screening
`Solvent effects and
`receptor flexibility
`
`Combining Pharmacophore Search, Automated Docking, and Molecular
`Dynamics Simulations as a Novel Strategy for Flexible Docking. Proof of
`Concept: Docking of Arginine−Glycine−Aspartic Acid-like Compounds into the
`α β Binding Site
`v 3
`
`Nicolas Moitessier, Christophe Henry, Bernard Maigret, and Yves Chapleur
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4178-4187 (Article)
`Publication Date (Web): July 20, 2004
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` Abstract
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` Full text
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` ABSTRACT
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`Validation of Automated Docking Programs for Docking and Database
`Screening against RNA Drug Targets
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`11/19
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`Carsten Detering and Gabriele Varani
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`Journal of Medicinal Chemistry 2004, 47, 17, 4188-4201 (Article)
`Publication Date (Web): July 13, 2004
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`Tricyclic Alkylamides as Melatonin Receptor Ligands with Antagonist or Inverse
`Agonist Activity
`
`Valeria Lucini, Marilou Pannacci, Francesco Scaglione, Franco Fraschini, Sivia Rivara, Marco Mor, Fabrizio Bordi,
`Pier Vincenzo Plazzi, Gilberto Spadoni, Annalida Bedini, Giovanni Piersanti, Giuseppe Diamantini, and Giorgio
`Tarzia
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`Journal of Medicinal Chemistry 2004, 47, 17, 4202-4212 (Article)
`Publication Date (Web): July 17, 2004
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` Abstract
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`A-348441
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`Liver-Selective Glucocorticoid Antagonists: A Novel Treatment for Type 2
`Diabetes
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`Thomas W. von Geldern, Noah Tu, Philip R. Kym, James T. Link, Hwan-Soo Jae, Chunqiu Lai, Theresa Apelqvist,
`Patrik Rhonnstad, Lars Hagberg, Konrad Koehler, Marlena Grynfarb, Annika Goos-Nilsson, Johnny Sandberg, Marie
`Österlund, Tomas Barkhem, Marie Höglund, Jiahong Wang, Steven Fung, Denise Wilcox, Phong Nguyen, Clarissa
`Jakob, Charles Hutchins, Mathias Färnegårdh, Björn Kauppi, Lars Öhman, and Peer B. Jacobson
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4213-4230 (Article)
`Publication Date (Web): July 13, 2004
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` Abstract
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`Solution Structure of Amyloid β-Peptide (25−35) in Different Media
`
`Anna M. D'Ursi, Maria R. Armenante, Remo Guerrini, Severo Salvadori, Giuseppe Sorrentino, and Delia Picone
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4231-4238 (Article)
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`Publication Date (Web): July 21, 2004
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`Journal of Medicinal Chemistry | Vol 47, No 17
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`
`
`
`Design, Synthesis, and Biological Evaluation of New Cyclic Disul de
`Decapeptides That Inhibit the Binding of AP-1 to DNA
`
`Keiichi Tsuchida, Hisaaki Chaki, Tadakazu Takakura, Junichi Yokotani, Yukihiko Aikawa, Shunichi Shiozawa, Hiroaki
`Gouda, and Shuichi Hirono
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4239-4246 (Article)
`Publication Date (Web): July 21, 2004
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` Abstract
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`Concise Synthesis and Structure−Activity Relationships of Combretastatin A-4
`Analogues, 1-Aroylindoles and 3-Aroylindoles, as Novel Classes of Potent
`Antitubulin Agents
`
`Jing-Ping Liou, Yi-Ling Chang, Fu-Ming Kuo, Chun-Wei Chang, Huan-Yi Tseng, Chiung-Chiu Wang, Yung-Ning Yang,
`Jang-Yang Chang, Shiow-Ju Lee, and Hsing-Pang Hsieh
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`Journal of Medicinal Chemistry 2004, 47, 17, 4247-4257 (Article)
`Publication Date (Web): July 17, 2004
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` Abstract
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`14/19
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`Three-Dimensional Quantitative Structure−Activity Relationship Analysis of a
`
`Set of Plasmodium falciparum Dihydrofolate Reductase Inhibitors Using a
`Pharmacophore Generation Approach
`
`Marco Daniele Parenti, Sara Pacchioni, Anna Maria Ferrari, and Giulio Rastelli
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4258-4267 (Article)
`Publication Date (Web): July 16, 2004
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` Abstract
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` Full text
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` ABSTRACT
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`2-(1-Adamantyl)-4-(thio)chromenone-6-carboxylic Acids: Potent Reversible
`Inhibitors of Human Steroid Sulfatase
`
`Amarylla Horvath, Peter Nussbaumer, Barbara Wolff, and Andreas Billich
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4268-4276 (Article)
`Publication Date (Web): July 9, 2004
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` Abstract
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` Full text
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`Phenoxyphenyl Pyridines as Novel State-Dependent, High-Potency Sodium
`Channel Inhibitors
`
`Bin Shao, Sam Victory, Victor I. Ilyin, R. Richard Goehring, Qun Sun, Derk Hogenkamp, Diane D. Hodges, Khondaker
`Islam, Deyou Sha, Chongwu Zhang, Phong Nguyen, Silvia Robledo, George Sakellaropoulos, and Richard B. Carter
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4277-4285 (Article)
`Publication Date (Web): July 16, 2004
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`https://pubs.acs.org/toc/jmcmar/47/17
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`15/19
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`
`Journal of Medicinal Chemistry | Vol 47, No 17
`
`
`
`
`Identi cation of Structurally Diverse Growth Hormone Secretagogue Agonists
`by Virtual Screening and Structure−Activity Relationship Analysis of 2-
`Formylaminoacetamide Derivatives
`
`Miyuki Shoda, Takeo Harada, Yuji Kogami, Ryuichi Tsujita, Hirotada Akashi, Hiroyuki Kouji, Florence L. Stahura, Ling
`Xue, and Jürgen Bajorath
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4286-4290 (Article)
`Publication Date (Web): July 13, 2004
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` Abstract
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`Piperazine Derivatives of [1,2,4]Triazolo[1,5-a][1,3,5]triazine as Potent and
`Selective Adenosine A Receptor Antagonists
`2a
`
`Chi B. Vu, Bo Peng, Gnanasambandam Kumaravel, Glenn Smits, Xiaowei Jin, Deepali Phadke, Thomas Engber,
`Carol Huang, Jennifer Reilly, Stacy Tam, Donna Grant, Gregg Hetu, Liqing Chen, Jianbo Zhang, and Russell C. Petter
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4291-4299 (Article)
`Publication Date (Web): July 13, 2004
`
` Abstract
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`https://pubs.acs.org/toc/jmcmar/47/17
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`16/19
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`Journal of Medicinal Chemistry | Vol 47, No 17
`Fluorescent Pirenzepine Derivatives as Potential Bitopic Ligands of the Human
`M1 Muscarinic Receptor
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`Chouaib Tahtaoui, Isabelle Parrot, Philippe Klotz, Fabrice Guillier, Jean-Luc Galzi, Marcel Hibert, and Brigitte Ilien
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`Journal of Medicinal Chemistry 2004, 47, 17, 4300-4315 (Article)
`Publication Date (Web): July 16, 2004
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` Abstract
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`Tetramethylcyclopropyl Analogue of a Leading Antiepileptic Drug, Valproic
`Acid. Synthesis and Evaluation of Anticonvulsant Activity of Its Amide
`Derivatives
`
`Eyal Sobol, Meir Bialer, and Boris Yagen
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4316-4326 (Article)
`Publication Date (Web): July 20, 2004
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`Zinc Ion Dependent B-Cell Epitope, Associated with Primary Sjogren's
`Syndrome, Resides within the Putative Zinc Finger Domain of Ro60kD
`Autoantigen: Physical and Immunologic Properties
`
`John G. Routsias, Aggeliki Kosmopoulou, Athina Makri, Eugenia Panou-Pomonis, Constantinos Sakarellos, Maria
`Sakarellos-Daitsiotis, Haralampos M. Moutsopoulos, and Athanasios G. Tzioufas
`
`Journal of Medicinal Chemistry 2004, 47, 17, 4327-4334 (Article)
`Publication Date (Web): July 17, 2004
`
`https://pubs.acs.org/toc/jmcmar/47/17
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`17/19
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`
`Journal of Medicinal Chemistry | Vol 47, No 17
`
`
`
`
`BRIEF ARTICLES
`
`O-Alkoxyamidine Prodrugs of Furamidine: In Vitro Transport and Microsomal
`Metabolism as Indicators of in Vivo E cacy in a Mouse Model of Trypanosoma
`brucei rhodesiense Infection
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`John H. Ansede, Mariappan Anbazhagan, Reto Brun, Judy D. Easterbrook, James Edwin Hall, and David W. Boykin
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`Journal of Medicinal Chemistry 2004, 47, 17, 4335-4338 (Brief Article)
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`•••
`Glucagon-like Peptide-1: The Basis of a New Class of Treatment
`for Type 2 Diabetes
`Lotte Bjerre Knudsen
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` Cite this: J. Med. Chem. 2004, 47, 17, 4128–4134
`Publication Date: July 20, 2004
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`https://doi.org/10.1021/jm030630m
`Copyright © 2004 American Chemical Society
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`Glucagon-like Peptide-1: The Basis of a New Class of Treatment for Type 2 Diabetes | Journal of Medicinal Chemistry
`SUBJECTS:
`Anatomy, Carbohydrates,
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`Glucagon-like Peptide-1: The Basis of a New Class of Treatment for Type 2 Diabetes | Journal of Medicinal Chemistry
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`Diabetes
`
`
`
`
`Lotte BjetTe Knuds en t
`Di.:rco~cry Biology 1\•fanogemcnt, Novo
`
`Rc.,dt.tcd Dt.-...imbcr 24, 2003
`
`'ortll~k. DK-27GO MoalootJ, Druim,ark
`
`lnti•oduction
`Type 2 diabetes is inct-easingly becoming a wod.dwide
`epidemic. Cm·rentJy there is much focus on t he gluca(cid:173)
`gon-like peptide- I (GLP-1) peptide hormone as the basis
`fol' a potenti.a] new treatment pamdlgm fot· type 2
`diabetes. The two major draw1backs of the dl'Ug1> cm~
`1-ent.ly utiliz d in t ho treatment of ty~ 2-d.iabetos m·
`th.at (l) du1•ing their l.ong-te1·m admini$tl·ation body
`weight incr·ease!o and (2), the disea~ progrei;;ses over
`ti me, also evidenced by an increasing l06r. of fJ•oelJ
`fun.ction.
`GLP-l! was discovered i:n 1984 and found to be 1m
`important iucret.in.1 It is a pt"Oduct of the p1-eprogluea(cid:173)
`gon gene an.d is 1"eleased from the L-cells i.n. the intestine
`upon food in:take and potently :releases insulin from the
`{J-,;ells in th pancreas.
`umerous effect.s other than
`s:timula tion of insulin release have been ascl'ibed to
`GLP-1. In the panct"eas, not only does GLP-1 l'elease
`insulin bltt it does so in a glu:oose-dependent manner, 2,l
`and it has a nl.lm.ber of other functional1y important
`effects: stimulation of insulin biosynthesis, 1-estol'ation
`of glucose sensitivity to the islets, and st:im.ul.ation of
`increased exp,,e.ssion of the gluoose t.ranspottel' GLUT-2
`and gluookina~.4 - 6 G-LP-1 also lrns a numbe1• of effects
`on 1-egulatfon of fi• c 11 ma!,s,: $1:;imulation of replieat.fon
`and growtJi and inhibitfon of apoptosii. of existing
`/J.cells, and neo·genesis or new /1-cells from dud pi-ecm~
`soi· eells.7•8 GLP-1 inhibits glucagon sec:retfon,9 which
`t en leads fo r • duced hepaf c g1ucose output.. I
`the gut.,
`GLP-1 is a potent inhibitol' of motilit.y and gastric
`emptying and has also been shown to inhibit gastric acid
`soc1"etion. 10 The inhibition of gastric mptyi.ng loads to
`decroased food intake and t'tlduood body weight, 11 ,1 ~
`Thus the cw·i, nt belief is that the GLP-1 compound
`class may be able to co.nt!'ol the progressi.on of the ty e
`2 diabete.s disease not only by controlling blood gluoose
`but a e.o via i:.evet·a othet· effect~. OLP-l bas also b n
`pt•oposed to h ave di.rec effects on glucose uptake in
`livet· 11u1,scle, and adjpose ti.ssue, hut the quantitative
`significance of the:re -effects h.as been questioned.13 New
`publications even sugge.st that the beneficial effect.a of
`GLP-1 compounds go beyond the tl'eatment of diabetes.
`There may be specific receptot-s i11 the h.eat-t that along
`with the benefits of 1-edltcing bloo glucose may protect
`f1"011n c.at"<lfovnscufor oom.pli.cation:s, H and GLP-i' stimu-
`1 ates memor'Y a.nd faa.mi ng capabili tfas. u. A oo,npt~hen(cid:173)
`siv(;! 1,eview exists on -he glue..ngon-like peptides. J3
`Clinically, GLP-1 has been shown to b very effective
`in lowering blood glucose in quit.. a broad ra1ige of
`
`' Ph~n.o: +4 5 1
`novonord:i.ak,com,
`
`diabetes stages.1,; Very important1y littJe risk of hy(cid:173)
`poglycaemia bas been observed.,~ Thls is because GLP-
`1, u:nlike sulfonylureas, only stimulates the natural
`gluoose-•induced insulin secretion. p to 6 wee,k studies
`h ave been performed with natural OLP·l in a subcu-
`1.aneous pu.mp. In his study a lowering of body veight
`w s also seen.12 he only known pha1•rrul.cologkal r.ide
`effect of GL ·l is MUlle-a Md vomiting when adminis(cid:173)
`tered in high doses. The-ee unwanted effect.i; a.re medj(cid:173)
`ated by inhibitoo. gastric 0mp ying. Howovet' the vast
`majot-:ity of cli11iclll data indicate- tbat th.o naUSf!d is
`transient and that efficient gluoose oontt"Ol can be
`obtained without this sid effect. 'I'l:ms, from a clinical
`point of view, GLP-1., with its efficacious lowel'i.ng of
`blood. g]ucose with little risk of hypog]ycemia and its
`pot.ential for pt"eventi.on of disease prog.-ession, seems
`ideal fot· the treatment of type 2 d:iabet.es.
`Tho GLP-1 t-oeeptor was cloned in 1992 and is a
`G-protein-ooupled l"eceptor from the B family also
`1·e.ferrnd to as the s001-etin/glucngon family.11 The ligands
`i.n this family aN nuiinly lal'ge peptide hormones., SmaU(cid:173)
`molecule antagonists especially fot· the glucagon nioop•
`tor have been described, but no s.mall-mofocule agonis ts
`have be.in. desci-ibed in th.e literature. Thus, the GLP~l
`based oompound class will most likely be pepti.des and
`the challenge is that tbe natural hormone i:s degraded
`rnpidly by the enzyme dipeptidyl peptidase IV (DDP(cid:173)
`IV) and cleai-ed. by the kidneys resul.Ung in a half-)ife
`of less than 2 min after iv administration and a
`cleamnoo higher than t11at of the not·mal cm-d.iac
`output. l -.v G LP• l exists in two equipoten natut·all.y
`occw>rin,g forms, GLP-1(7- 37) and. GLP-1(7 - 36)amide,
`Lhe fo1~me1· corf'esponding to Jlf'Oglucngon(78- 108}. The,
`nu1nber'ing of GLP·l st.ad t; with ? because it WM
`ol'igirul ly believed ~hal G
`-l(l-37) WM the active
`hormone. It wa,1; lat.er djscove1-ed that Ute real ho!'mon.e
`was formed after cl-eaving off lhe fil"St 6 N-t.errn..inal
`amino acids and then the 7 numbering system begun.
`The primary metabolite ofGLP- , GLP-1(9-36) amide
`or GLP-1(9•-31) has a gl.'eat)y decJ"eased affinity for the
`GLP- l! NOO tor and may even b8 an a11tagonist 01· a
`partial agonist. The m.agnitude and dul'll.tion of the
`blood glucose lowering ability of natural GLP-1 ha.Ye
`boon sh.own to be dependent on a continuous supply of
`pha1mo.colog:ical levels_21 T hus, the efficacy of II OLP-
`1-like drug wiU be dependent on t-he duration of action
`of Lhe compound Oi' the for1nul ,tion even though s.o1ne
`of the long~tet·m benefits of GLP-1 compounds, 1ike
`inc1·•.n1sing ti-cell mass, may not t-equfre constantly
`elevated GLP-l levels. Another potential limitation is
`tha the on1y known phat·macologica1ly indaced side
`0ffect is nausea occurring via the inhibition of gastric
`
`10.1021Jjm030080m
`
`=. $27.50 __ @ 2004 Ameriean • hemi~l _ ociecy-
`Pubbshed on Web 07/20/2004
`
`† Phone: +45 44434788. Fax: +45 44663939. E-mail: lbkn@ novonordisk.com.
`
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`Glucagon-like Peptide-1: The Basis of a New Class of Treatment for Type 2 Diabetes | Journal of Medicinal Chemistry
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