Peptidomimetics Protocols

ISBN-13: 9780896035171 / Angielski / Twarda / 1998 / 549 str.

Wieslaw M. Kazmierski

Opis

Many physiologically important receptors and enzymes are regulated by their endogenous ligands and inhibitors. Nature chose to utilize these p- tides as chemical switches since they can be efficiently synthesized and - graded in cells, thus providing an immediate response to a fast changing environment. Such properties, so critical in cell survival, make peptides less than ideal drug candidates. Other frequently desired properties in drug m- ecules include oral bioavailability, the ability to cross membranes, including the blood-brain barrier, and sufficient stability for administration 1-2 times a day. In spite of these obstacles, some natural peptides and proteins are ind- putably successful medicines and have become drugs of choice. Further - vances in peptide-based pharmaceuticals are critically dependent on both new delivery methods and new chemical approaches to the conversion of these molecules to druglike entities. In addition, peptides are also the natural sta- ing points for optimization of their pharamacological and chemical prop- ties, which may lead to superior drugs. Peptidomimetics Protocols deals with both aspects of peptide pharmaceuticals, through the tools of modern s- thetic and medicinal chemistry. The last decade has witnessed a steady stream of new synthetic approaches to peptide mimetics, compounds that replace phy- ologically vulnerable peptide functionalities with chemical modules of - creased stability and cellular penetration. The chapters have been written by both academic and industrial chemists, and focus on the practical synthetic preparation of peptide mimetics.

Recenzje

"The editor has assembled an interesting collection of synthetic methods for preparing peptidomimetics. . .This book will clearly be of value to those who are interested in synthesizing nonpeptidic analogues of small peptide ligands."-Journal of Medicinal Chemistry

"the editor does an excellent job of bringing together a variety of different chemical syntheses that are relevant to peptide, peptidomimetic, combinatorial and medicinal chemistry. Each chapter is written in the same general format of introduction, materials, methods, notes and references, which is always valuable for a book that will be regularly consulted. In addition, many of these are reported by acknowledged leaders in the field. . . includes a number of novel amino acid syntheses that will be extremely
valuable to those scientists trying to understand the underlying medicinal chemistry of peptides. . . the contents of this book are extremely valuable and I have no doubt it will find its way into many of the world's leading industrial and academic organic chemistry laboratories."-Drug Discovery Today

Spis treści

Synthesis and Use of Pseudopeptides Derived from 1,2,4-Oxadiazole-, 1,3,4-Oxadiazole-, and 1,2,4-Triazole-based Dieptidomimetics, Kristina Luthman, Susanna Borg, and Uli Hacksell. Syntheses of FMOC-2,3-Methanoleucine Stereoisomers and their Incorporation into Peptidomimetics, Kevin Burgess and Wen Li. Synthesis of an Esterase-Sensitive Cyclic Prodrug of a Model Hexapeptide Having Enhanced Membrane Permeability and Enzymatic Stability Using an Acyloxyalkoxy Promoiety, Sanjeev Gangwar, Giovanni M. Pauletti, Teruna J. Siahaan, Valentino J. Stella, and Ronald T. Borchardt. Synthesis of an Esterase-Sensitive Cyclic Prodrug of a Model Hexapeptide Having Enhanced Membrane Permeability and Enzymatic Stability Using a 3-(2'-Hydroxy-4',6'-Dimethylphenyl)-3,3-Dimethyl Propionic Acid Promoiety, Binghe Wang, Sanjeev Gangwar, Giovanni Pauletti, Teruna Siahaan, and Ronald T. Borchardt. Synthesis of Coumarin-Based, Esterase-Sensitive Cyclic Prodrugs of Opioid Peptides with Enhanced Membrane Permeability and Enzymatic Stability, Binghe Wang, Daxian Shan, Wei Wang, Huijuan Zhang, Olafur Gudmundsson, and Ronald T. Borchardt. Azatides as Peptidomimetics: Solution and Liquid Phase Syntheses, Hyunsoo Han, Juyoung Yoon, and Kim D. Janda. Synthesis of Cbz-Protected Ketomethylene Dipeptide Isosteres, Robert V. Hoffman and Junhua Tao. (E)-Alkene Peptide Bond Isosteres by Cuprate Opening of Vinyl Aziridines, Todd C. Henninger and Peter Wipf. Syntheses of Norstatine, Its Analogs, and Dipeptide Isosteres by Means of ß-Lactam Synthon Method, Iwao Ojima and Francette Delaloge. Synthesis of a Versatile Peptidomimetic Scaffold, Stephen Hanessian and Grant McNaughton-Smith. An Asymmetric Synthesis Protocol to Prepare Topographically Constrained ß-Substituted Aromatic Amino Acids, Subo Liao and Victor J. Hruby. Synthesis of Oligopeptides Containing an Oxirane Ring in the Place of a Peptidic Bond, Maurizio Taddei. Synthesis of Protected Lactam-Bridged Dipeptides, Debra S. Perlow and Roger M.Freidinger. Synthesis of Peptidomimics Through Sugar-Based Scaffolds, Yves Le Merrer, Lydie Poitout, and Jean-Claude Depezay. The Synthesis of Bicyclic Piperazinone and Related Derivatives, Yvette M. Fobian and Kevin D. Moeller. Synthesis of Dipeptides with y[CH2O] Amide Bond Mimetics, Wieslaw M. Kazmierski and Paul C. Fritch. SNAr-Based Cycloetherification Methodology: Application in the Synthesis of Heterodectic Macrocyclic Peptides with Endo Aryl-Aryl and Aryl-Alkyl Ether Bonds, Jieping Zhu. Cyclic Aromatic Amino Acids with Constrained c1 and c2 Dihedral Angles, Dirk Tourwé, Koen Iterbeke, Wieslaw M. Kazmierski, and Géza Tóth. Asymmetric Syntheses of Unnatural Amino Acids and Hydroxyethylene Peptide Isosteres, Robert M. Williams. Fluoroolefin Isosteres, J.T. Welch and T. Allmendinger. Synthesis of 3-Amino-1-Carboxymethyl-Benzodiazepine (BZA) Peptidomimetics, James C. Marsters, Jr. and Thomas E. Rawson. A Conformationally Restricted ß-Strand HIV Protease Inhibitor, Michael C. Hillier and Stephen F. Martin. Synthesis of Cyclopropane-Containing Leu-Enkephalin Analogs, Michael P. Dwyer and Stephen F. Martin. The 1,5-Disubstituted Tetrazole Ring as a cis-Amide Bond Surrogate, Janusz Zabrocki and Garland R. Marshall. Synthesis of (2R, 3R, 4R, 5S)-5-tert- Butyloxycarbonylamino-3,4-Dihydroxy-2-Isopropyl-3,4-O,O-Isopropylidene-6-Cyclohexyl-Hexanoic Acid, Allen Scott, Brian G. Conway, and Mark A. Krook. Synthesis of (2S, 4S, 5S)-5-(t-Butoxycarbonylamino)- 4-(t-Butyldimethylsilyloxy)-2-Isopropyl-7-Methyl Octanoic Acid, Mark A. Lyster and Brian G. Conway. Synthesis of a-Vinyl Amino Acids, David B. Berkowitz, Jill M. McFadden, Marianne K. Smith, and Michelle L. Pedersen. A Novel Synthetic Protocol for the Preparation of Enantiopure 3-, 4-, and 5-Substituted Prolines, N. André Sasaki. Synthesis of Aminobenzoic Acid-Based Nonpeptide Templates: Applications in Peptidomimetic Drug Discovery, Kimberly S. Para and Tomi K. Sawyer. Aminimides as Peptidomimetics,

Blurb

In Peptidomimetics Protocols, Wieslaw Kazmierski assembles a state-of-the-art collection of detailed synthetic procedures that lead to a variety of scaffolds, turn mimetics, peptide-bond replacements, and enzyme inhibitors. Topics range from syntheses of unusual amino acids, to the use of a variety of linear and heterocyclic scaffolds in place of the peptide backbone. Important chemical procedures and methods include the transient protection of charged peptides as neutral prodrugs for improved blood-brain penetration and the replacement of otherwise labile peptide bonds with heterocyclic rings, olefins and fluoroolefins, and ketomethylenes. Synthetic protocols towards the transition-state mimics and reactive "warheads," applicable in enzyme inhibitors, are also disclosed.

Peptidomimetics Protocols is the first book devoted to the practical synthetic preparation of peptide mimetics. Written by both academic and industrial synthetic organic and medicinal chemists, this book provides highly practical synthetic procedures for the generation of key peptide mimetics, and so immediately becomes a must-have desk reference and guide for all medicinal and pharmaceutical chemists engaged in the discovery and development of pharmaceuticals today.