Frontiers in Medicinal Chemistry

Volume 1


Atta-ur-Rahman, Allen B. Reitz

DOI: 10.2174/97816080520421040101
eISBN: 978-1-60805-204-2, 2004
ISBN: 978-1-60805-672-9
ISSN: 1567-2042 (Print)
ISSN: 1875-5763 (Online)

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Table of Contents


- Pp. i
Atta-ur-Rahman, M. Iqbal Choudhary, Allen B. Reitz and Cheryl P. Kordik
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Targeting Protein Kinases for Bone Disease: Discovery and Development of Src Inhibitors

- Pp. 3-27 (25)
Chester A. Metcalf, Marie Rose van Schravendijk, David C. Dalgarno and Tomi K. Sawyer
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Inhibitors of Matrix Metalloproteinases: Design, Structure and Therapeutic Applications

- Pp. 29-75 (47)
Jerry W. Skiles, Nina C. Gonnella and Arco Y. Jeng
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Mechanism-based Inhibition of Metalloproteinases

- Pp. 77-83 (7)
Dong H. Kim and Shahriar Mobashery
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Selective COX-2 Inhibitors and Dual Acting Anti-inflammatory Drugs: Critical Remarks

- Pp. 85-95 (11)
A. Bertolini, A. Ottani and M. Sandrini
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Protein Farnesyltransferase Inhibitors

- Pp. 97-128 (32)
Semiramis Ayral-Kaloustian and Edward J. Salaski
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The Design of Competitive, Small-molecule Inhibitors of Coagulation Factor Xa

- Pp. 129-152 (24)
Henry W. Pauls, William R. Ewing and Yong Mi Choi-Sledeski
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Small Molecule Activators of the Insulin Receptor: Potential New Therapeutic Agents for the Treatment of Diabetes Mellitus

- Pp. 153-164 (12)
Edgardo Laborde and Vara Prasad Manchem
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Current Therapies and Emerging Targets for the Treatment of Diabetes

- Pp. 165-187 (23)
Allan S. Wagman and John M. Nuss
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Designed Enediyne Antitumor Agents

- Pp. 189-214 (26)
G.B. Jones and F.S. Fouad
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Combinatorial Approaches in Anticancer Drug Discovery: Recent Advances in Design and Synthesis

- Pp. 215-235 (21)
Sukanta Bhattacharyya
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The Expanding Role of NMR in Rational Drug Design

- Pp. 237-271 (35)
Rickey P. Hicks and Daniel A. Nichols
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Mass Spectrometry Based Assays for Drug Screening in the Early Phases of Drug Discovery

- Pp. 273-292 (20)
Marshall M. Siegel
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Recent Advances in PDE4 Inhibitors as Immunoregulators and Antiinflammatory Drugs

- Pp. 293-345 (53)
Catherine Burnouf, Ingrid Devillers and Marie-Pierre Pruniaux
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Serotonin Reuptake Inhibition: An Update on Current Research Strategies

- Pp. 347-359 (13)
D. Spinks and G. Spinks
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Emerging ő≤-Amyloid Therapies for the Treatment of Alzheimer's Disease

- Pp. 361-384 (24)
Kelly A. Conway, Ellen W. Baxter, Kevin M. Felsenstein and Allen B. Reitz
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Oxidative Stress in Animal Models of Accelerated Aging, Alzheimer’s Disease and Huntington’s Disease

- Pp. 385-397 (13)
D. Allan Butterfield
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Constitutive Activity of Brain Serotonin Receptors: Inverse Agonist Activity of Antipsychotic Drugs

- Pp. 399-408 (10)
Anil Purohit, Katharine Herrick-Davis and Milt Teitler
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Physicochemical Profiling (Solubility, Permeability and Charge State)

- Pp. 409-475 (67)
Alex Avdeef
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Non-peptide Opioid Receptor Ligands - Recent Advances. Part I - Agonists

- Pp. 477-500 (24)
Agnieszka Kaczor and Dariusz Matosiuk
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Nitric Oxide Therapies in Vascular Diseases

- Pp. 501-512 (12)
E.M. Kurowska
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Strategies to Improve Stability and Bioavailability of Peptide Drugs

- Pp. 513-528 (16)
Céline Adessi and Claudio Soto
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The Role of Genomics in the Discovery of Novel Antibacterial Targets

- Pp. 529-542 (14)
Jerry M. Buysse
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New Anti-HIV Agents in Preclinical or Clinical Development

- Pp. 543-579 (37)
Erik De Clercq
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DNA Minor Groove Alkylators

- Pp. 581-594 (14)
William A. Denny
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Applications of Small Molecule Crystallography and the Cambridge Structural Database in Drug Design

- Pp. 595-606 (12)
Johan Wouters and Frédéric Ooms
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Compound Optimization in Early and Late Phase Drug Discovery: Acceptable Pharmacokinetic Properties Utilizing Combined Physicochemical, In Vitro and In Vivo Screens

- Pp. 607-618 (12)
Gary W. Caldwell
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DNA-binding of Drugs Used in Medicinal Therapies

- Pp. 619-645 (27)
G. Bischoff, S. Hoffmann and R. Zhdanov
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The Contribution of Combinatorial Chemistry to Lead Generation: An Interim Analysis

- Pp. 647-662 (16)
Anton E.P. Adang and Pedro H.H. Hermkens
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New Paradigms in Drug Design and Discovery

- Pp. 663-681 (19)
Joseph J. Barchi and Nouri Neamati
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Author Index

- Pp. 683
Atta-ur-Rahman and Allen B. Reitz
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Subject Index

- Pp. 685-688 (4)
Atta-ur-Rahman and Allen B. Reitz
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Medicinal Chemistry has matured as a discipline, and there is no better time than the present to be a medicinal chemist. One of the primary driving forces in this renaissance is the increased value added by collaborations with biology, pharmacology, toxicology, spectroscopy, and allied fields earlier in the drug discovery process. The modern practicing medicinal chemist is inundated with new data, including in vitro and in vivo ADME profiling, which enables informed decisions that increase the likelihood of success in the future. This first issue of Frontiers in Medicinal Chemistry is being published only online, allowing for rapid and broad dissemination of the material presented. The chapters are selected from issues of Current Medicinal Chemistry, Current Topics in Medicinal Chemistry and Current Pharmaceutical Design to represent a cross-section of the most compelling subjects and developments in medicinal and bioorganic chemistry. The manuscripts and topics are clustered thematically, and overall constitute a substantial and impressive body of knowledge. The authors were given the opportunity to update their contributions, and many chose to do that. It is expected that Frontiers will be published on an annual basis in future years. Our thanks to Matthew Honan of Bentham Science Publishers for providing this opportunity.

Prof. Atta-ur-Rahman
Prof. M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
University of Karachi
Karachi 75270

Allen B. Reitz, Ph.D.
Cheryl P. Kordik, Ph.D.
Johnson & Johnson Pharmaceutical
Research and Development
Spring House, Pennsylvania 19477

List of Contributors

Prof Atta-ur-Rahman FRS
University of Cambridge

Allen B. Reitz
Johnson & Johnson Pharmaceutical Research and Development
Spring House Pennsylvania

Associate Editor(s):
M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
University of Karachi
Karachi, 75270

Cheryl P. Kordik
Johnson & Johnson Pharmaceutical Research and Development
Spring House, Pennsylvania

Editorial Advisory Board:
P.R Bernstein
University of Delaware

C. Bor-Luen
National Taiwan University

R. Efremov
M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry

C. Garcia-Echeverria

D. Hadjipavlou-Litina
Arristotle Universith of Thessaloniki

D. Heymann
University of Nantes

D.A. Jans
Nuclear Signaling Laboratory, Monash University

G.B. Mahady
University of Illinois at Chicago

B. Malawska
Jagiellonian University Collegium Medicum

C. Philippe
Sciences and Technologies University of Lille


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