Medicinal Chemistry and Drug Development
- 1st Edition - February 5, 2025
- Editor: Gang Liu
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 2 7 4 0 2 - 2
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 2 7 4 0 3 - 9
Medicinal Chemistry and Drug Development describes the key events and roles of medicinal chemistry in the discovery and development of lead compounds into drugs, including target… Read more
Medicinal Chemistry and Drug Development describes the key events and roles of medicinal chemistry in the discovery and development of lead compounds into drugs, including target identification, which is accomplished by using 30 case studies. This book outlines all the stages of drug development, including the discovery of active compounds, research on the pharmacological
properties of molecules, and confirmation of drug targets. The role of the case studies is to show the common factors in the successful development of drugs, thereby showing medicinal chemists how best to explore the scientific pathways when developing new drugs. This makes the book especially relevant for senior university students majoring in pharmaceutical sciences as well as graduate students and researchers.
properties of molecules, and confirmation of drug targets. The role of the case studies is to show the common factors in the successful development of drugs, thereby showing medicinal chemists how best to explore the scientific pathways when developing new drugs. This makes the book especially relevant for senior university students majoring in pharmaceutical sciences as well as graduate students and researchers.
- Provides unique information on different drug development case studies
- Integrates pharmaceutical knowledge—mainly medicinal chemistry—with new drug development thinking
- Describes using case studies, the impact of key events in drug development and on drug efficacy
Senior university students majoring in pharmaceutical sciences and graduate students
1. Medicinal chemistry and process development of the type 2 diabetes drug sitagliptin
1.1 Introduction to the type 2 diabetes drug sitagliptin
1.2 Incretin and its degrading enzyme dipeptidyl peptidase-4
1.3 Property-based drug design
1.4 Common factors influencing the ADME/T properties of drugs
1.5 Early pharmacological and toxicological studies of dipeptidyl peptidase IV inhibitors
1.6 Confirmation of lead compounds
1.7 Optimization of the β-amino acid series lead compounds
1.8 Clinical studies of the new drug sitagliptin
1.9 Process chemistry of sitagliptin
2. The developmental history of insulin pharmaceuticals
2.1 Introduction to diabetes and insulin
2.2 Development of insulin pharmaceuticals
2.3 Summary and outlook
3. The developmental trajectory of GLP-1 receptor agonists
3.1 Glucagon-like peptide-1 (GLP-1)
peptide-1 (GLP-1)
3.2 The development of GLP-1 therapeutics
3.3 The unsuccessful case in GLP-1 drug R&D and the implications and lessons
3.4 Summary and outlook
4.1 Factors related to the onset of diabetes
4.2 Sodium-glucose cotransporter 2 (SGLT2) inhibitors as anti-diabetic drugs
4.3 Successful experience in the development of dapagliflozin
5. Cholesterol-lowering drug atorvastatin
5.1 Hypercholesterolemia and cardiovascular diseases
5.2 Atorvastatin, the cholesterol-lowering drug
5.3 Medicinal chemistry of atorvastatin
5.4 Summary and outlook
6. Angiotensin II receptor antagonists for treatment of hypertension: the discovery of losartan and its analogs
6.1 Brief introduction of hypertension and commonly used medications for the treatment of hypertension
6.2 The renin-angiotensin system
6.3 Angiotensin II receptor antagonists
6.4 Discovery of losartan
6.5 Discovery of losartan analogs
7. Antithrombotic drug—apixaban
7.1 What is thrombosis?
7.2 Treatment of thrombosis
7.3 The medicinal chemistry of apixaban
7.4 Clinical indications of apixaban
7.5 Postclass requirements and references
8. Development of the anticoagulant drug fondaparinux sodium
8.1 Thrombotic disorders
8.2 Functions of factor Xa
8.3 Treatment of thrombotic disorders
8.4 Discovery and history of anticoagulant drug: fondaparinux sodium
8.5 Chemical process of fondaparinux sodium
8.6 Summary
9. Development of the nucleotide antiviral drug sofosbuvir for the hepatitis C virus
9.1 Hepatitis C and hepatitis C virus
9.2 Hepatitis C virus biology
9.3 Discovery of sofosbuvir
9.4 Clinical studies of sofosbuvir
9.5 Summary and outlook
10. The first HIV-1 integrase inhibitor, raltegravir
10.1 AIDS and HIV
10.2 Anti-HIV drugs
10.3 The discovery journey of raltegravir
10.4 Research on the synthetic process of raltegravir
10.5 Summary and knowledge expansion
11. Discovery and development of the human immunodeficiency virus protease inhibitor Saquinavir
11.1 Overview of virus
11.2 Human immunodeficiency virus and acquired immunodeficiency syndrome
11.3 HIV protease and inhibitor saquinavir
11.4 Further development of Saquinavir
11.5 Anti-HIV/AIDS drugs and novel treatment strategies
12. Baloxavir: an antiinfluenza drug with a novel mechanism of action
12.1 Influenza virus
12.2 Antiinfluenza drugs
12.3 Development of baloxavir
13. Paclitaxel: a natural antitumor agent
13.1 Discovery and development of taxol
13.2 The pharmaceutical chemistry of paclitaxel
13.3 Design strategy for paclitaxel prodrugs
13.4 Summary and outlook
14. Antitumor drug eribulin
14.1 Introduction
14.2 Antitumor mechanism of eribulin
14.3 The development process of eribulin
14.4 Pharmacological characteristics of eribulin
14.5 Clinical research and safety evaluation of eribulin
14.6 Conclusion
15. Targeted protein kinase inhibitor imatinib
15.1 Protein kinases (PKs) and protein kinase inhibitors (PKIs) as antineoplastic agents
15.2 Medicinal chemistry of imatinib
15.3 Imatinib resistance and solutions
15.4 Summary
16. A case study of the irreversible covalent epidermal growth factor receptor (EGFR) inhibitor—afatinib
16.1 Preface
16.2 Epidermal growth factor receptor and quinazoline-based small molecule inhibitors
16.3 Drug design based on covalent inhibition strategies
16.4 Development of covalent irreversible EGFR inhibitor2 afatinib
16.5 Synthesis of afatinib
16.6 Summary and knowledge expansion
17. Medicinal chemistry and process development of the antibreast cancer drug tamoxifen
17.1 Estrogen receptors and breast cancers
17.2 The medicinal chemistry of the selective estrogen receptor modulator tamoxifen
17.3 Clinical investigations of tamoxifen
17.4 Summary, knowledge expansion, and references
18. Triazole antifungal drug—fluconazole
18.1 Overview of fungal infections
18.2 Overview of antifungal drugs
18.3 The developmental history of fluconazole
18.4 Structure optimization of fluconazole: development of new generation triazole antifungal drugs
19. Discovery of the antibacterial drug Linezolid and its synthetic technology research
19.1 Development of antibacterial agents
19.2 Discovery of the antibacterial drug Linezolid
19.3 Bioactivity and pharmacokinetics of antibacterial drug Linezolid
19.4 The antibacterial mechanisms of Linezolid
19.5 Study on structure-activity relationship of oxazolidinone antibiotics
19.6 Research on the synthesis process of Linezolid
19.7 Conclusion
20. Carbapenem antibiotic meropenem
20.1 Introduction
20.2 Bacterial resistance and special use level antibacterial drugs
20.3 Case of meropenem
20.4 The progress on other carbapenem antibiotics
21. Antiparasitic drug praziquantel
21.1 Parasitic diseases
21.2 Antiparasitic drug praziquantel
21.3 Medicinal chemistry of praziquantel
21.4 Green process for praziquantel and its levoisomer
21.5 Green chemistry future
22. A case study on the proton pump inhibitor omeprazole
22.1 Peptic ulcers
22.2 Why is omeprazole
22.3 Medicinal chemistry of omeprazole
22.4 Clinical applications of omeprazole
22.5 Summary and knowledge expansion
23. The inhibitors of phosphodiesterase type 5A effectively treat erectile dysfunction
23.1 The nitric oxide-cyclic guanosine monophosphate signaling pathway associated with penile erectile function
23.2 Sildenafil for the management of male erectile dysfunction
23.3 The approval of second and thirdgeneration highly selective phosphodiesterase type 5A inhibitors
23.4 Synthesis of selective phosphodiesterase type 5A inhibitors
23.5 Molecular mechanisms of phosphodiesterase type 5A inhibitors
23.6 Summary and prospect
24. GABAA receptor agonists: discovery of the general anesthetic propofol and its analogs
24.1 Introduction to anesthesia 585
24.2 Common drugs in clinical anesthesia
24.3 Medicinal chemistry of the general intravenous anesthetic propofol and its analogs
25. The discovery of risperidone: a case of multiple target antipsychotic drug
25.1 Antipsychotic drugs
25.2 Medicinal chemistry of risperidone
25.3 Characteristics of risperidone’s effects
26. A case study on the first-in-class antirenal anemia drug roxadustat
26.1 Renal anemia and its pathogenesis
26.2 Medications for the treatment of renal anemia
26.3 Development process of roxadustat
26.4 Conclusion
27. Function, pharmaceutical, and pharmacological research and development of natural tetracyclic dipyranocoumarin (1)-calanolide A and its analogs
27.1 Discovery and structural diversity of natural tetracyclic dipyranocoumarins
27.2 Natural nonnucleoside reverse transcriptase inhibitors
27.3 Anti-HIV-1 activity of improved calanolides
27.4 (1)-Calanolide A and its derivatives inhibit replicating and non-replicating Mycobacterium tuberculosis
27.5 Fluorescent activity of nitrofuran derivatives: a revelatory outcome
28. Bisphosphonates: a targeted therapeutic medication for skeletal system
28.1 Unveiling the saga of bisphosphonates
28.2 Elucidating the mechanisms of action of bisphosphonate drugs
28.3 Medicinal chemistry of nitrogencontaining bisphosphonates
28.4 Novel applications of bisphosphonate inhibitors
29. Celecoxib targets cyclooxygenase in nonsteroidal antiinflammatory drugs
29.1 Nonsteroidal antiinflammatory drugs and cyclooxygenase
29.2 Selective cyclooxygenase-2 inhibitor celecoxib
29.3 Other representative coxib drugs
29.4 Summary and perspective
30. Case study of antisense oligonucleotides for duchenne muscular dystrophy
30.1 Introduction
30.2 Duchenne muscular dystrophy
30.3 Mechanism of action of antisense oligonucleotide drugs
30.4 The developmental trajectory of antisense oligonucleotide therapeutics targeting the DMD gene
30.5 Summary and outlook
1.1 Introduction to the type 2 diabetes drug sitagliptin
1.2 Incretin and its degrading enzyme dipeptidyl peptidase-4
1.3 Property-based drug design
1.4 Common factors influencing the ADME/T properties of drugs
1.5 Early pharmacological and toxicological studies of dipeptidyl peptidase IV inhibitors
1.6 Confirmation of lead compounds
1.7 Optimization of the β-amino acid series lead compounds
1.8 Clinical studies of the new drug sitagliptin
1.9 Process chemistry of sitagliptin
2. The developmental history of insulin pharmaceuticals
2.1 Introduction to diabetes and insulin
2.2 Development of insulin pharmaceuticals
2.3 Summary and outlook
3. The developmental trajectory of GLP-1 receptor agonists
3.1 Glucagon-like peptide-1 (GLP-1)
peptide-1 (GLP-1)
3.2 The development of GLP-1 therapeutics
3.3 The unsuccessful case in GLP-1 drug R&D and the implications and lessons
3.4 Summary and outlook
4.1 Factors related to the onset of diabetes
4.2 Sodium-glucose cotransporter 2 (SGLT2) inhibitors as anti-diabetic drugs
4.3 Successful experience in the development of dapagliflozin
5. Cholesterol-lowering drug atorvastatin
5.1 Hypercholesterolemia and cardiovascular diseases
5.2 Atorvastatin, the cholesterol-lowering drug
5.3 Medicinal chemistry of atorvastatin
5.4 Summary and outlook
6. Angiotensin II receptor antagonists for treatment of hypertension: the discovery of losartan and its analogs
6.1 Brief introduction of hypertension and commonly used medications for the treatment of hypertension
6.2 The renin-angiotensin system
6.3 Angiotensin II receptor antagonists
6.4 Discovery of losartan
6.5 Discovery of losartan analogs
7. Antithrombotic drug—apixaban
7.1 What is thrombosis?
7.2 Treatment of thrombosis
7.3 The medicinal chemistry of apixaban
7.4 Clinical indications of apixaban
7.5 Postclass requirements and references
8. Development of the anticoagulant drug fondaparinux sodium
8.1 Thrombotic disorders
8.2 Functions of factor Xa
8.3 Treatment of thrombotic disorders
8.4 Discovery and history of anticoagulant drug: fondaparinux sodium
8.5 Chemical process of fondaparinux sodium
8.6 Summary
9. Development of the nucleotide antiviral drug sofosbuvir for the hepatitis C virus
9.1 Hepatitis C and hepatitis C virus
9.2 Hepatitis C virus biology
9.3 Discovery of sofosbuvir
9.4 Clinical studies of sofosbuvir
9.5 Summary and outlook
10. The first HIV-1 integrase inhibitor, raltegravir
10.1 AIDS and HIV
10.2 Anti-HIV drugs
10.3 The discovery journey of raltegravir
10.4 Research on the synthetic process of raltegravir
10.5 Summary and knowledge expansion
11. Discovery and development of the human immunodeficiency virus protease inhibitor Saquinavir
11.1 Overview of virus
11.2 Human immunodeficiency virus and acquired immunodeficiency syndrome
11.3 HIV protease and inhibitor saquinavir
11.4 Further development of Saquinavir
11.5 Anti-HIV/AIDS drugs and novel treatment strategies
12. Baloxavir: an antiinfluenza drug with a novel mechanism of action
12.1 Influenza virus
12.2 Antiinfluenza drugs
12.3 Development of baloxavir
13. Paclitaxel: a natural antitumor agent
13.1 Discovery and development of taxol
13.2 The pharmaceutical chemistry of paclitaxel
13.3 Design strategy for paclitaxel prodrugs
13.4 Summary and outlook
14. Antitumor drug eribulin
14.1 Introduction
14.2 Antitumor mechanism of eribulin
14.3 The development process of eribulin
14.4 Pharmacological characteristics of eribulin
14.5 Clinical research and safety evaluation of eribulin
14.6 Conclusion
15. Targeted protein kinase inhibitor imatinib
15.1 Protein kinases (PKs) and protein kinase inhibitors (PKIs) as antineoplastic agents
15.2 Medicinal chemistry of imatinib
15.3 Imatinib resistance and solutions
15.4 Summary
16. A case study of the irreversible covalent epidermal growth factor receptor (EGFR) inhibitor—afatinib
16.1 Preface
16.2 Epidermal growth factor receptor and quinazoline-based small molecule inhibitors
16.3 Drug design based on covalent inhibition strategies
16.4 Development of covalent irreversible EGFR inhibitor2 afatinib
16.5 Synthesis of afatinib
16.6 Summary and knowledge expansion
17. Medicinal chemistry and process development of the antibreast cancer drug tamoxifen
17.1 Estrogen receptors and breast cancers
17.2 The medicinal chemistry of the selective estrogen receptor modulator tamoxifen
17.3 Clinical investigations of tamoxifen
17.4 Summary, knowledge expansion, and references
18. Triazole antifungal drug—fluconazole
18.1 Overview of fungal infections
18.2 Overview of antifungal drugs
18.3 The developmental history of fluconazole
18.4 Structure optimization of fluconazole: development of new generation triazole antifungal drugs
19. Discovery of the antibacterial drug Linezolid and its synthetic technology research
19.1 Development of antibacterial agents
19.2 Discovery of the antibacterial drug Linezolid
19.3 Bioactivity and pharmacokinetics of antibacterial drug Linezolid
19.4 The antibacterial mechanisms of Linezolid
19.5 Study on structure-activity relationship of oxazolidinone antibiotics
19.6 Research on the synthesis process of Linezolid
19.7 Conclusion
20. Carbapenem antibiotic meropenem
20.1 Introduction
20.2 Bacterial resistance and special use level antibacterial drugs
20.3 Case of meropenem
20.4 The progress on other carbapenem antibiotics
21. Antiparasitic drug praziquantel
21.1 Parasitic diseases
21.2 Antiparasitic drug praziquantel
21.3 Medicinal chemistry of praziquantel
21.4 Green process for praziquantel and its levoisomer
21.5 Green chemistry future
22. A case study on the proton pump inhibitor omeprazole
22.1 Peptic ulcers
22.2 Why is omeprazole
22.3 Medicinal chemistry of omeprazole
22.4 Clinical applications of omeprazole
22.5 Summary and knowledge expansion
23. The inhibitors of phosphodiesterase type 5A effectively treat erectile dysfunction
23.1 The nitric oxide-cyclic guanosine monophosphate signaling pathway associated with penile erectile function
23.2 Sildenafil for the management of male erectile dysfunction
23.3 The approval of second and thirdgeneration highly selective phosphodiesterase type 5A inhibitors
23.4 Synthesis of selective phosphodiesterase type 5A inhibitors
23.5 Molecular mechanisms of phosphodiesterase type 5A inhibitors
23.6 Summary and prospect
24. GABAA receptor agonists: discovery of the general anesthetic propofol and its analogs
24.1 Introduction to anesthesia 585
24.2 Common drugs in clinical anesthesia
24.3 Medicinal chemistry of the general intravenous anesthetic propofol and its analogs
25. The discovery of risperidone: a case of multiple target antipsychotic drug
25.1 Antipsychotic drugs
25.2 Medicinal chemistry of risperidone
25.3 Characteristics of risperidone’s effects
26. A case study on the first-in-class antirenal anemia drug roxadustat
26.1 Renal anemia and its pathogenesis
26.2 Medications for the treatment of renal anemia
26.3 Development process of roxadustat
26.4 Conclusion
27. Function, pharmaceutical, and pharmacological research and development of natural tetracyclic dipyranocoumarin (1)-calanolide A and its analogs
27.1 Discovery and structural diversity of natural tetracyclic dipyranocoumarins
27.2 Natural nonnucleoside reverse transcriptase inhibitors
27.3 Anti-HIV-1 activity of improved calanolides
27.4 (1)-Calanolide A and its derivatives inhibit replicating and non-replicating Mycobacterium tuberculosis
27.5 Fluorescent activity of nitrofuran derivatives: a revelatory outcome
28. Bisphosphonates: a targeted therapeutic medication for skeletal system
28.1 Unveiling the saga of bisphosphonates
28.2 Elucidating the mechanisms of action of bisphosphonate drugs
28.3 Medicinal chemistry of nitrogencontaining bisphosphonates
28.4 Novel applications of bisphosphonate inhibitors
29. Celecoxib targets cyclooxygenase in nonsteroidal antiinflammatory drugs
29.1 Nonsteroidal antiinflammatory drugs and cyclooxygenase
29.2 Selective cyclooxygenase-2 inhibitor celecoxib
29.3 Other representative coxib drugs
29.4 Summary and perspective
30. Case study of antisense oligonucleotides for duchenne muscular dystrophy
30.1 Introduction
30.2 Duchenne muscular dystrophy
30.3 Mechanism of action of antisense oligonucleotide drugs
30.4 The developmental trajectory of antisense oligonucleotide therapeutics targeting the DMD gene
30.5 Summary and outlook
- Edition: 1
- Published: February 5, 2025
- Language: English
GL
Gang Liu
Professor Gang Liu has been engaged in research on medicinal chemistry and chemical biology for over 30 years. He studied at The Scripps Research Institute and the University of California, Davis in the United States. Since 2011, he has been a "Tenure-Track Professor" at Tsinghua University, Vice Dean of School of Medicine, and was responsible for the establishment of the Department of Pharmaceutical Sciences (now the School of Pharmaceutical Sciences) at Tsinghua University.
Affiliations and expertise
Tsinghua UniversityRead Medicinal Chemistry and Drug Development on ScienceDirect