Antineoplastic Drugs E-Book

Daniel Lednicer

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 306

Veröffentlichungsjahr: 2015

Beschreibung

The past decade has seen a significant increase of research aimed at discovering new drugs for treating cancer, and the increasing number of new antineoplastic drugs approved by regulatory agencies reflects this. Until now, details on the synthesis of these newer agents have been scattered in various journals and in US and European patents. This timely volume deals with the organic chemistry involved in the synthesis of the agents found within antineoplastic drugs, including descriptions of the synthetic schemes for the preparation of over 200 compounds that have been granted non-proprietary names. Compounds are collected in chapters based on the mechanism of action rather than on their chemical structures. Each individual chapter is preceded by a brief description of that mechanism and includes detailed flow charts of the preparation of those compounds accompanied by discussions of the organic chemistry involved in each step. The first half of this volume is dedicated to the syntheses of established chemotherapy drugs. Kinase inhibitors occupy the following chapters with the largest single chapter dealing with the fifty compounds that inhibit tyrosine kinase. This class stands out since over twenty compounds in this group have been approved for treating patients; a rare track record compared to any other class of therapeutic agents. Antineoplastic Drugs: Organic Syntheses is written to appeal to organic and medicinal chemists in industry and academia. It is beneficial to those composing grant proposals for NCI and related organizations. The book is accessible to advanced undergraduates as well as graduates and researchers as well as those with a thorough grasp of organic chemistry.

Leseprobe

CONTENTS

Cover

Title page

Preface

Introduction

References

1 Alkylating Agents

1.1 bis-Chloroethyl Amines

1.2 Several Other Chloroethyl Agents

1.3 Platinum-Based Antineoplastic Agents

1.4 Miscellaneous Alkylating Agents

References

2 Antimetabolites

2.1 Introduction

2.2 Folate Antagonists

2.3 Pyrimidines and Purines

References

3 Hormone Blocking Anticancer Drugs

3.1 Introduction

3.2 Estrogen Antagonists

3.3 Androgen Antagonists

References

4 Topoisomerase Inhibitors

4.1 Introduction

4.2 Anthracyclines

4.3 Anthraquinones and Anthrapyrazoles

4.4 Camptothecins

4.5 Miscellaneous Topoisomerase Inhibitors

References

5 Mitotic Inhibitors

5.1 Introduction

5.2 Taxanes

5.3 Wholly Synthetic Compounds

References

6 Matrix Metalloproteinase Inhibitors

6.1 Introduction

6.2 Hydroxamates

References

7 Histone Deacetylase Inhibitors

7.1 Introduction

7.2 Hydroxamates

7.3 Phenylenediamines

References

8 Enzyme Inhibitor, Part I, Tyrosine Kinases

8.1 Introduction

8.2 Epidermal Growth Factor Inhibitors

8.3 VEGF

8.4 SRC Nonreceptor Tyrosine Kinase

8.5 PDGF

8.6 EGF

8.7 Other TKI

8.8 Janus Kinase Inhibitors

References

9 Enzyme Inhibitors: Part II Additional Targets

9.1 Serine–Threonine Kinase Inhibitors

9.2 Additional Enzyme Inhibitors

References

10 Miscellaneous Antineoplastic Agents

10.1 Acyclic

10.2 Monocyclic

10.3 Two Linked Rings

10.4 Rings on a Chain

10.5 Fused Rings

References

Appendix A

Combinatorial Chemistry

Index of Heterocycle Syntheses

Subject Index

End User License Agreement

List of Tables

Chapter 08

Table 8.1 Tyrosine kinase factors

List of Illustrations

Introduction

Scheme 1 Methchloramine.

Chapter 01

Scheme 1.1 Aziridinium salt formation.

Scheme 1.2 Synthesis of mustine.

Scheme 1.3 Cyclophosphamide.

Scheme 1.4 Estramustine.

Scheme 1.5 Canfosfamide.

Scheme 1.6 Nitrosoureas.

Scheme 1.7 Cloretazine.

Scheme 1.8 Cisplatin synthesis.

Scheme 1.9 Enloplatin.

Scheme 1.10 Oxaliplatin.

Scheme 1.11 Picoplatin.

Scheme 1.12 Imexon.

Scheme 1.13 Apaziquone.

Scheme 1.14 Temozolamide.

Chapter 02

Scheme 2.1 Targets of Antimetabolites.

Scheme 2.2 Methotrexate.

Scheme 2.3 Edatrexate.

Scheme 2.4 Pralatrexate.

Scheme 2.5 Lometrexol.

Scheme 2.6 Ralitrexed.

Scheme 2.7 Pelitrexol.

Scheme 2.8 Pemetrexed.

Scheme 2.9 Trimetrexate.

Scheme 2.10 Piritrexim.

Scheme 2.11 5-Fluorouracil.

Scheme 2.12 6-Mercaptopurine.

Scheme 2.13 Cytarabine.

Scheme 2.14 Gemcitabine.

Scheme 2.15 Tezacitabine.

Scheme 2.16 Sapacitabine.

Scheme 2.17 Decitabine.

Scheme 2.18 Fazarabine.

Scheme 2.19 Nelarabine.

Scheme 2.20 Cladribine.

Scheme 2.21 Fludarabine.

Chapter 03

Scheme 3.1 Clomiphene.

Scheme 3.2 Tamoxifen.

Scheme 3.3 Other “fenes.”

Scheme 3.4 Lasofoxifene.

Scheme 3.5 Raloxifene.

Scheme 3.6 Bazedoxifene.

Scheme 3.7 Fulvestrant.

Scheme 3.8 Estradiol from testosterone.

Scheme 3.9 Formestane.

Scheme 3.10 Exemestane.

Scheme 3.11 Aminoglutethimide.

Scheme 3.12 Fadrozole.

Scheme 3.13 Letrozole.

Scheme 3.14 Anastrozole.

Scheme 3.15 Vorozole.

Scheme 3.16 5α-reductase.

Scheme 3.17 Flutamide and Nilutamide.

Scheme 3.18 Bicalutamide.

Scheme 3.19 Andarine.

Scheme 3.20 Bexlosteride.

Scheme 3.21 Finasteride.

Scheme 3.22 Dutasteride.

Scheme 3.23 Abiraterone.

Scheme 3.24 Galeterone.

Scheme 3.25 Dromostanolone.

Scheme 3.26 Bolasterone and calusterone.

Chapter 04

Scheme 4.1 Rubicin antineoplastic agents.

Scheme 4.2 Idarubicin.

Scheme 4.3 Amrubicin A.

Scheme 4.4 Amrubicin B.

Scheme 4.5 Ametantrone.

Scheme 4.6 Mitoxantrone.

Scheme 4.7 Piroxantrone.

Scheme 4.8 Losoxantrone.

Scheme 4.9 Pixantrone.

Scheme 4.10 Topixantrone.

Scheme 4.11 Bisantrene.

Scheme 4.12 Camptothecin and camptogen.

Scheme 4.13 Irinotecan.

Scheme 4.14 Belotecan.