Reviews: 2019 Medicinal Chemistry Reviews

1. Introduction
2. A Love of Chemistry
3. The Halcyon Days of Pharma
4. Leukotrienes and the Wittig Reaction
5. Structure-Based Drug Design
6. Cobalt Route to Macrocyclic Kinase Inhibitors
7. Peptide-Mimetics of Apolipoprotein A1
8. Conclusion

1. Introduction
2. Therapeutic Approaches to Sickle Cell Disease
3. Conclusions

1. Introduction
2. Small-Molecule PAR-1 Antagonists in the Prevention and Treatment of Arterial Thrombotic Events
3. Small-Molecule PAR-4 Antagonists in the Prevention and Treatment of Arterial Thrombotic Events
4. Conclusion

1. Introduction
2. Current Marketed Therapies
3. Preclinical Small Molecules Targeting IPF
4. Conclusions

1. Introduction
2. IRAK4 Role in Inflammatory and Oncology Diseases
3. Scope and Strategy of Review
4. IRAK4 Protein Structure and Key Amino Acids Involved in Small-Molecule Interactions
5. Recent Advances in Medicinal Chemistry
6. Preclinical In Vivo Efficacy Studies
7. Clinical Trials with IRAK4 Inhibitors
8. Conclusions

1. Introduction
2. Design of Small Molecules Disrupting the TNF-α Trimer
3. Design of Small Molecules Inhibiting TNF Transmembrane Type 1 and Type 2 Receptors
4. Conclusions

1. Introduction
2. Biochemistry of IDH Enzymes
3. Discovery of Gain-of-Function IDH Mutations
4. Cancer Biology of Oncometabolite 2-HG
5. Mutant IDH2 Inhibitors: AGI-6780, AG-221 (Enasidenib)
6. Mutant IDH1 Inhibitors: AG-881 (Vorasidenib), AGI-5198, ML309, AG-120 (Ivosidenib), IDH889, IDH305, LY 3410738, FT-2102 (Olutasidenib), BAY 1436032, MRK-A
7. Acquired Drug Resistance and Future Directions

1. Introduction
2. Recent DHODH Inhibitor Chemotypes
3. Emerging Clinical DHODH Inhibitors
4. Concluding Remarks

1. Introduction
2. STING Agonist Therapeutic Concept for Immuno-Oncology
3. STING Structural Information and Biophysical Assays
4. Cyclic Dinucleotides (CDNs)
5. STING Agonists
6. Conclusion and Future Perspective

1. Introduction
2. Glycosylphosphatidylinositol Anchor Biosynthesis and Function
3. Gwt1 Inhibitor Chemotypes
4. Optimization of BIQ to Manogepix (APX001A)
5. In Vitro and In Vivo Profile of Manogepix/Fosmanogepix
6. Manogepix Analogs with Improved Activity Against Cryptococcus
7. Conclusion

1. Introduction
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3. Limitations of Previous NNRTIs
4. Medicinal Chemistry Efforts Leading to Doravirine
5. Doravirine Early Clinical Profile: ADME, PK-PD, and Tolerability
6. Clinical Trials of Doravirine
7. Future Directions
8. Conclusions

1. Introduction
2. Recent Progress Towards Boronate-Based β-Lactamase Inhibitors and Penicillin-Binding Protein Inhibitors
3. New Diazabicyclooctane-Based Inhibitors
4. Siderophore β-Lactam Conjugates
5. Other Clinical Results
6. Conclusions

1. Introduction
2. Principles for Targeting RNA with Small Molecules
3. Examples of RNA as a Small-Molecule Drug Target
4. Future Outlook

1. Introduction
2. Covalent Chemical Probes and Chemoproteomics
3. Conclusions

1. Introduction
2. Physiological Properties of the Blood-Brain Barrier
3. Predicting Brain Penetration
4. Conclusion

1. Introduction
2. Solubility-Enhancing Prodrugs
3. Permeability-Enhancing Prodrugs
4. Transporter-Targeted Prodrugs
5. Site-Specific Prodrugs
6. Sustained Release Prodrugs
7. Other Prodrugs
8. Conclusion

1. Introduction
2. Structure and Catalytic Mechanism of DUBs
3. Assay Technologies
4. Discovery and Development of DUB Inhibitors
5. Conclusions and Future Perspectives

1. Introduction
2. ClpP Protease: Structure and Mechanism of Action
3. Inhibition of ClpP Protease
4. Activation of ClpP Protease
5. Targeting of AAA+ ClpP Unfoldases
6. Conclusions

1. Introduction
2. Lead Generation and SAR
3. Synthesis
4. Pre-Clinical Studies
5. Clinical Studies
6. Conclusions

1. Introduction
2. Medicinal Chemistry Efforts Leading to the Discovery of Talazoparib
3. Scale-up Process Development for Talazoparib
4. Preclinical Characterization of Talazoparib
5. Clinical Results and FDA Approval
6. Conclusion

1. Amifampridine (Lambert-Eaton myasthenic syndrome)
2. Apalutamide (anticancer)
3. Avatrombopag (chronic liver disease)
4. Baloxavir Marboxil (antiviral)
5. Bictegravir (antiviral)
6. Binimetinib (anticancer)
7. Cannabidiol (seizures)
8. Dacomitinib (anticancer)
9. Doravirine (antiviral)
10. Duvelisib (anticancer)
11. Elagolix (endometriosis)
12. Elobixibat (constipation)
13. Encorafenib (anticancer)
14. Eravacycline (antibacterial)
15. Evocalcet (hyperparathyroidism)
16. Fosravuconazole (antifungal)
17. Fostamatinib (thrombocytopenia)
18. Fruquintinib (anticancer)
19. Gilteritinib (anticancer)
20. Glasdegib (anticancer)
21. Ivosidenib (anticancer)
22. Larotrectinib (anticancer)
23. Lofexidine (opiate withdrawal)
24. Lorlatinib (anticancer)
25. Moxidectin (onchocerciasis)
26. Omadacycline (antibacterial)
27. Omidenepag (glaucoma)
28. Plazomicin (antibacterial)
29. Plitidepsin (anticancer)
30. Prucalopride (constipation)
31. Pyrotinib (anticancer)
32. Revefenacin (chronic obstructive pulmonary disease)
33. Rifamycin (antibacterial)
34. Roxadustat (antianemic)
35. Sarecycline (antibacterial)
36. Stiripentol (Dravet syndrome)
37. Tafenoquine (malaria)
38. Talazoparib (anticancer)
39. Tecovirimat (antiviral)
40. Tegoprazan (antacid)
41. Tezacaftor (cystic fibrosis)
42. Vibegron (overactive bladder)

1. Albuvirtide (HIV-1)
2. Burosumab (X-linked hypophosphatemia)
3. Caplacizumab (acquired thrombotic thrombocytopenic purpura)
4. Cemiplimab (advanced cutaneous squamous cell carcinoma)
5. Emapalumab (primary hemophagocytic lymphohistiocytosis)
6. Erenumab (migraine)
7. Fremanezumab (migraine)
8. Galcanezumab (migraine)
9. Ibalizumab (HIV-1)
10. Inotersen (polyneuropathy of hereditary transthyretin-mediated amyloidosis)
11. Lanadelumab (hereditary angioedema)
12. Moxetumomab pasudotox (hairy cell leukemia)
13. Patisiran (polyneuropathy of hereditary transthyretin-mediated amyloidosis)
14. Ravulizumab (paroxysmal nocturnal hemoglobinuria)
15. Tagraxofusp (blastic plasmacytoid dendritic cell neoplasm)
16. Tildrakizumab (psoriasis)