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Pharmaceutical
Chemistry
Mukesh Chandra Joshi
TM
Krishan Kumar
Distributed by:
Pharmaceutical Chemistry
Mukesh Chandra Joshi
Assistant Professor
Department of Chemistry
Motilal Nehru College
South Campus, BJ Marg
University of Delhi
Krishan Kumar
Assistant Professor
Department of Chemistry
Motilal Nehru College
South Campus, BJ Marg
University of Delhi
Pharmaceutical Chemistry
Authors: Mukesh Chandra Joshi
Published by I.K. International Pvt. Ltd.
4435, 36/7, Ansari Rd, Daryaganj, New Delhi, Delhi 110002
ISBN: 978-93-91029-32-6
EISBN: 978-93-91029-05-0
©Copyright 2021 I.K. International Pvt. Ltd., New Delhi-110002.
This book may not be duplicated in any way without the express written consent of the publisher, except in the
form of brief excerpts or quotations for the purposes of review. The information contained herein is for the
personal use of the reader and may not be incorporated in any commercial programs, other books, databases, or
any kind of software without written consent of the publisher. Making copies of this book or any portion for any
purpose other than your own is a violation of copyright laws.
Limits of Liability/disclaimer of Warranty: The author and publisher have used their best efforts in preparing
this book. The author make no representation or warranties with respect to the accuracy or completeness of the
contents of this book, and specifically disclaim any implied warranties of merchantability or fitness of any
particular purpose. There are no warranties which extend beyond the descriptions contained in this paragraph.
No warranty may be created or extended by sales representatives or written sales materials. The accuracy and
completeness of the information provided herein and the opinions stated herein are not guaranteed or warranted
to produce any particulars results, and the advice and strategies contained herein may not be suitable for every
individual. Neither Dreamtech Press nor author shall be liable for any loss of profit or any other commercial
damages, including but not limited to special, incidental, consequential, or other damages.
Trademarks: All brand names and product names used in this book are trademarks, registered trademarks, or
trade names of their respective holders. Dreamtech Press is not associated with any product or vendor mentioned
in this book.
Preface
We take this opportunity to introduce the present book to our esteemed colleagues and
enthusiastic students. The need of international pharmaceutical content is yet not fulfilled
in Indian varsities. We have tried to put our sincere efforts to meet the prevailing scarcity
of comprehensive study material through this book.
Drug discovery programs, world over, have proactively engaged the scientists in
designing novel medicinal scaffolds. Wherein structural modification and structural
activity relationship has been instrumental succeeding such programs. New synthetic
routes and structural elucidation are followed to evaluate scaffolds confirming the desired
biological activity. It led us to systematic research in pharmaceutics giving rise to synthetic
drugs. Heterocycles are the key components in pharmaceutical chemistry, demonstrating
numerous biological properties.
Pharmaceutical chemistry has always been an exciting branch of organic chemistry,
particularly correlating the theoretical outcomes with synthetic methods and stability of
the molecule designed. Pharmaceutical Chemistry comprises the knowledge of chemical
biology, computational chemistry, medical, enzymology and structural biology which is
useful in studying the scientific aspects of the drug discovery programs of new therapeutic
agents. The emphasis is always on the chemical reactions and interactions involved in a
drug therapy.
The present manuscript is designed for the undergraduate students pursuing BSc (H),
BSc (Physical Sciences) in all central and state universities under CBCS scheme that can
also be consulted by Pharma students. The content of this book is specially designed for
the BSc (H), BSc (Physical Sciences), Skill Enhancement Course (SEC) Sem-III and Sem-IV
under the UGC-CBCS scheme. We have covered the complete syllabus related to
pharmaceutical chemistry including chemical and biological interfaces. The undergraduate
students will achieve a solid background in various aspects of pharmaceutical chemistry
pertaining to the drugs development. They will also learn the fundamental aspects of the
synthesis, manufacturing, usage, and mode of action of drugs and other biological aspects.
The standard of undergraduate student has been consistently in focus while preparing
the content. Further, the limitations of bilingual or incumbent English readers are specially
taken care of throughout the work. At the same time, the quality of the content has nowhere
been compromised. We have consulted and updated the contents of international standard.
vi Preface
We have exploited this opportunity with an aim to produce quality content for further
studies.
Moreover, the interdisciplinary readers have also been under consideration to increase
the coverage area across discipline. Lastly, no effort is beyond the scope of improvement
and we have been entering into process of producing world-class material for our colleagues
and students as well. We are nowhere hesitant to incorporate any suggestions that can
transform the current book into more useful and standard piece of work in later editions.
Mukesh Chandra Joshi
Krishan Kumar
Acknowledgements
It is too difficult to acknowledge all the direct/indirect contributors, motivational
personalities for authoring an academic document where one is limited both by words and
space. At the same time, acknowledgement of this piece of work is to accept the generosity
received from our teachers, parents and seniors both academically and socially.
We express our sincere gratitude to Prof. Dr. Diwan S. Rawat (Dept. of Chemistry,
University of Delhi, India), Dr. Santosh Pasha (Ex. Chief Scientist, CSIR-IGIB, Delhi, India),
Prof. Dr. Timothy J. Egan (Dept. of Chemistry, University of Cape Town, South Africa),
and Dr. Rakesh Shukla (Ex. Chief Scientist, CSIR-CDRI, Lucknow) for their incessant
guidance, keen interest, constant encouragement and support.
We are also thankful to our senior colleagues Dr. A. M. Khan, Dr. Y. Sharma, Dr. V.
Pradhan, Dr. N. K. Agnihotri, Dr. R. Kashyap and fellow teachers Dr. S. Tehlan, Dr. S.
Aggarwal, Dr. R. B. Pachwarya, Dr. S. K. Mangawa, and Dr. M. Kumar, at the Department
of Chemistry, Motilal Nehru College, University of Delhi. Moreover, in chair principals
have also been supportive for this academic assignment.
Without family support, no academic assignment can be accomplished perfectly;
therefore, we acknowledge the consistent and inspirational support received from our
respected parents, family members, friends and particularly from Dr. Beena and Dr.
Mohini.
Further, we thank the support we got from CSIR-IGIB faculties, Department of
Chemistry, University of Delhi, India and Department of Chemistry, Cape Town University,
RSA.
We lastly express our gratitude to those who could not be included here.
Mukesh Chandra Joshi
Krishan Kumar
Contents
Preface v
Acknowledgements vii
1. Drug Discovery, Design and Development 1
1.1 Introduction 1
1.2 Revolutions in Drug Discovery 3
1.3 Drug Discovery: A Historical Perspective 5
1.4 Drug Discovery and Development Processes 8
1.5 Modern Approach of Research and Development Strategies 15
1.6 Role of Natural Products in Target Identification 22
1.7 Bioisosterism 24
1.8 Role of Stereochemistry in Drug Discovery 25
Questions 27
2. Basic Retrosynthetic Approach 28
2.1 Introduction 28
2.2 Retrosynthetic Analysis: The Concepts 29
2.3 Basic Synthetic Strategies: General Approaches Used for Synthesis Problems 34
2.4 Retrosynthetic Analysis: Other Simplification Rules 39
2.5 Retrosynthetic Analysis: Synthetic Impropriety to Avoid 41
Questions 55
3. Analgesics, Antipyretic and Anti-Inflammatory Agents 57
3.1 Introduction 57
3.2 Classification 59
3.3 Mechanism of Action 60
3.4 Analgesic Agents 61
3.5 Anti-Inflammatory Drugs 62
3.6 Opioid Receptor Discovery 64
3.7 Aspirin 68
3.8 Ibuprofen 71
x Contents
3.9 Paracetamol 76
3.10 Diclofenac 80
Questions 83
4. Antibiotic, Antibacterial and Antifungal Agents 85
4.1 Introduction 85
4.2 Antibacterial Agents 87
4.3 Antifungal Agents 89
4.4 Chloramphenicol 94
4.5 Sulfonamides 95
4.6 Sulfamethoxazole 102
4.7 Sulfacetamide 103
4.8 Trimethoprim 105
Questions 108
5. Central Nervous System Agents 109
5.1 Introduction 109
5.2 Drugs Acting on CNS and Peripheral Nervous System (PNS) 115
5.3 Barbiturates 118
Questions 128
6. Cardiovascular Drugs 130
6.1 Introduction 130
6.2 Cardiovascular Drugs 130
6.3 Organic Nitrates 154
Questions 157
7. Anti-Leprosy Drugs 158
7.1 Introduction 158
7.2 The Organism 159
7.3 Drug Testing Systems 159
7.4 Chemotherapy 160
7.5 Classification of Leprosy and the Clinical Symptoms 161
7.6 Leprosy Co-existing Factors 162
7.7 Dapsone 162
7.8 Clofazimine (Lamprene) 166
7.9 Solapsone (Sulphetrone) 169
7.10 Ethionamide (Ethionamidum) 171
7.11 Rifampicin (Rifampin) 172
7.12 Clarithromycin 174
7.13 Minocycline 175
Contents xi
7.14 Other Sulfone Derivatives Active Against Leprosy 176
7.15 Treatment of Leprosy Using Chaulmoogra Oil 177
7.16 WHO Recommended Chemotherapeutic Regimens 178
Questions 180
8. HIV-AIDS: Antiviral Agents 181
8.1 Introduction 181
8.2 Structure of Viruses 181
8.3 Life Cycle of Viruses 182
8.4 Antiviral Drug Targets 185
8.5 Antiviral Drugs Acting Against RNA Viruses: HIV 196
8.6 Acquired Immune Deficiency Syndrome (AIDS) 200
Questions 207
9. Antimalarial Agents 208
9.1 Introduction 208
9.2 Life Cycle of the Malaria Parasite 209
9.3 Antimalarial Drugs 211
9.4 National Drug Policy on Malaria 227
9.5 WHO Guidelines for the Treatment of Malaria 230
Questions 231
10. Fermentation 233
10.1 Introduction 233
10.2 Production of Ethyl Alcohol and Citric Acid 236
10.3 Production of Antibiotics 239
10.4 Production of Lysine 246
10.5 Production of Glutamic Acid 247
10.6 Production of Vitamin B2 (Riboflavin) 251
10.7 Microbial Production of Vitamin B12 252
10.8 Production of Vitamin C (Ascorbic Acid) 253
Questions 258
11. Medicinal Importance of Curcumin, Neem, Vitamin C, Ranitidine,
Ginger, Tulsi, Garlic and Ajwain 259
11.1 Medicinal Importance of Haldi or Curcumin (Curcuma longa) 259
11.2 Medicinal Importance of Neem (Azadirachta indica) 261
11.3 Medicinal Value of Vitamin C (Ascorbic acid) 265
11.4 Medicinal Importance of Ranitidine 268
11.5 Medicinal Importance of Ginger (Zingiber officinale) 269
11.6 Medicinal Importance of Tulsi (Ocimum tenuiflorum) 273