Reviews: 2018 Medicinal Chemistry Reviews

Ref. n°: REV2018

Volume :	53
Editor-In-Chief :	Joanne J. Bronson

Medicinal Chemistry Reviews is an outstanding 680 page volume providing timely and critical reviews of important topics in medicinal chemistry. It is provided free of charge to MEDI members in electronic format. Members can also order a print copy, for the cost of printing, shipping and handling

Chapter 1	Diversity and Me: My Life as a Woman in Chemistry Diversity and Me: My Life as a Woman in Chemistry 1. Introduction 1 2. My Chemistry Journey Begins 2 3. Early Years at Merck: Renin Inhibitors and β3 AR Agonists 4 4. My Career at a Crossroads: Initiation of the DPP-4 Inhibitor Program 7 5. Development of Sitagliptin and the Back-up Program Leading to Omarigliptin 10 6. Diversity Matters 11 7. Life After Merck 13 8. Lessons Learned 14 9. Closing Words 15 Ann E. Weber
Chapter 2	A Journey in Cardiovascular Drug Discovery: New Frontiers and Lessons Learned A Journey in Cardiovascular Drug Discovery: New Frontiers and Lessons Learned 1. The Early Years 17 2. DuPont: The Angiotensin II Era (1982-1991) 18 3. A Focus on Antithrombotics: Discovery of Apixaban (1991-2001) 21 4. Bristol-Myers Squibb: Cardiovascular Drug Discovery (2001-present) 26 5. My Reflections: The Past, the Present, and the Future 31 Ruth Wexler
Chapter 3	Recent Advances in the Development of Phosphodiesterase 10A Tracers for Positron Emission Tomography Imaging Recent Advances in the Development of Phosphodiesterase 10A Tracers for Positron Emission Tomography Imaging 1. Introduction 41 2. [¹⁸F] and [¹¹C] Analogs of MP-10 43 3. [¹⁸F]-AMG 580 44 4. [¹¹C]-Lu AE92686 45 5. [¹¹C]MK-8193 46 6. [¹¹C]IMA107 47 7. [¹⁸F] and [¹¹C] Analogs of T-773 47 8. Conclusion 49 Essa Hu
Chapter 4	Pharmacology and Therapeutic Potential of the 5-HT7 Receptor: Beyond the Central Nervous System Pharmacology and Therapeutic Potential of the 5-HT7 Receptor: Beyond the Central Nervous System 1. Introduction 53 2. Respiratory System 56 3. Micturition (Urination) 57 4. Gastrointestinal Function and Inflammatory Bowel Disease (IBD) 58 5. Mammary Gland 60 6. Cancer and Fibrosis 61 7. Conclusions 62 Kevin M. Blattner, Daniel J. Canney, Benjamin E. Blass and Douglas A. Pippin
Chapter 5	Recent Progress in Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors for the Treatment of Parkinson's Disease Recent Progress in Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors for the Treatment of Parkinson's Disease 1. Introduction 67 2. Discovery of Key Compounds 68 2.1 Aminopyrimidines 69 2.2 Pyrrolopyrimidines 70 2.3 Indazoles 71 3. Structural Biology 72 4. Clinical Progress 76 5. Conclusions 77 Douglas S. Williamson, Morten Jørgensen and Kenneth V. Christensen
Chapter 6	Emerging Targets for the Treatment of Non-Alcoholic Steatohepatitis (NASH) Emerging Targets for the Treatment of Non-Alcoholic Steatohepatitis (NASH) 1. Introduction 87 2. Metabolic Mechanisms 89 2.1 Farnesoid X Receptor (FXR) 89 2.2 Peroxisome Proliferator Activated Receptors (PPARs) 92 2.3 Glucagon-Like Peptide-1 (GLP-1) Analogs 94 2.4 Fibroblast Growth Factor 19 (FGF-19) 95 2.5 Fibroblast Growth Factor 21 (FGF-21) 96 2.6 Acetyl-CoA Carboxylase (ACC) 97 2.7 Thyroid Hormone Receptor (THR) 98 3. Hepatic Necrosis Mechanisms 99 3.1 Apoptosis Signal-Regulating Kinase (ASK1) 99 4. Inflammatory Mechanisms 101 4.1 Chemokine Receptors 2 and 5 (CCR-2/CCR-5) 101 5. Fibrotic Mechanisms 102 5.1 Galectin 3 (Gal-3) 102 5.2 Lysyl Oxidase-Like 2 (LOXL-2) 103 6. Conclusions 103 Peter T.W. Cheng, James R. Corte, Alicia Regueiro-Ren and Dong Cheng
Chapter 7	Injectable Diabetes Treatments Targeting Glucose Regulation and Satiety Pathways Injectable Diabetes Treatments Targeting Glucose Regulation and Satiety Pathways 1. Introduction 113 2. Peptide Design Considerations 114 3. Glucagon-Like Peptide 1 117 4. Peptide YY 120 5. Oxyntomodulin and Polyagonists 128 6. Conclusion 130 James C. Lanter, Yue-Mei Zhang and Mark J. Macielag
Chapter 8	Discovery and Therapeutic Relevance of Small-Molecule NOX4 Inhibitors Discovery and Therapeutic Relevance of Small-Molecule NOX4 Inhibitors 1. Introduction 135 2. NADPH Oxidases 136 3. Medical Significance 137 4. Medicinal Chemistry and Natural Products 139 4.1 Requirements for Nox4 Assays 139 4.2 Natural Products That Inhibit Nox4 Expression 140 4.3 Natural products That Inhibit Nox4 Activity 142 4.4 Synthetic Nox4 Inhibitors 143 5. Conclusions and Future Directions 147 E. Blake Watkins, Osman F. Güner, Amol Kulkarni, Bernard Lassègue, Kathy K. Griendling and J. Phillip Bowen
Chapter 9	Recent Advances in the Discovery of Inhaled Anti-Inflammatory Treatments Recent Advances in the Discovery of Inhaled Anti-Inflammatory Treatments 1. Introduction 155 1.1 Disease Background 155 1.2 Inhaled Anti-Inflammatory Drugs Used in the Treatment of Asthma and COPD 156 2. Inhaled Delivery—Medicinal Chemistry Design Approaches 157 2.1 Inhaled Drug Delivery 157 2.2 Lung Pharmacokinetics 158 2.3 Blood Pharmacokinetics 159 3. Inhaled Small-Molecule Anti-Inflammatory Agents 160 3.1 Inhaled Kinase Inhibitors 160 3.1.1 p38 Inhibitors 160 3.1.2 JAK Inhibitors 162 3.1.3 PI3K Inhibitors 164 3.2 Inhaled Non-Kinase Anti-Inflammatory Agents 165 3.2.1 PDE4 Inhibitors 165 3.2.2 Adenosine A_2A Receptor Agonists 168 3.2.3 Non-Steroidal Glucocorticoid Receptor Modulators 169 3.2.4 Toll-Like Receptor Agonists 170 4. Conclusions 171 Peter Sjö, Frank Narjes and Martin Hemmerling
Chapter 10	Advances in the Discovery and Development of Selective Tyrosine Kinase 2 (TYK2) Inhibitors Advances in the Discovery and Development of Selective Tyrosine Kinase 2 (TYK2) Inhibitors 1. Introduction 178 1.1 TYK2, Janus Kinases, and Cytokine Signaling 178 1.2 Genetic Validation for TYK2 Inhibition 179 1.3 Clinical Utility of JAK Inhibitors 180 1.4 Clinical Validation of TYK2-Dependent Cytokine Pathways 180 1.4.1 p40 Cytokines (IL-12, IL-23) 181 1.4.2 Type I IFN 181 1.5 TYK2 Structure, Interdomain, and Cytokine Receptor Interactions 181 2. JH1 Domain Ligands as Inhibitors of TYK2 182 2.1 Imidazopyridines 182 2.2 Pyridinylpyrrolidinones 183 2.3 3-Amino-1,5-dihydro-4H-pyrazolopyridin-4-ones 184 2.4 6,7-Dihydro-5H-pyrrolo[3,4-b]pyridin-5-ones 185 2.5 Pyrazolo[1,5-A]pyrazines 186 2.6 Aminopyrimidines 187 2.7 Oxazole 4-carboxamides 188 3. JH2 Domain Ligands as Inhibitors of TYK2 189 3.1 Pseudokinases and Structure of TYK2 JH2 189 3.2 Thiazolopyridine and Imidazopyridine TYK2 JH2 Ligands 192 3.3 Imidazopyridazine TYK2 JH2 Ligands 194 4. Clinical Development of Selective TYK2 Inhibitors 195 5. Conclusion 196 David S. Weinstein and Ryan M. Moslin
Chapter 11	Covalent Inhibitors as Anti-Inflammatory Agents Covalent Inhibitors as Anti-Inflammatory Agents 1. Introduction 203 2. Covalent Inhibitors for Inflammatory Indications 205 2.1 Proteases 205 2.1.1 Methionine Aminopeptidase Type 2 205 2.1.2 Fatty Acid Amide Hydrolase 206 2.1.3 5-Lipoxygenase 209 2.2 Nuclear Receptors 210 2.2.1 Synthetic Glucocorticoids 210 2.3 Inflammasome and Proteasome 211 2.3.1 NLRP3 Inflammasome 211 2.3.2 Low-Molecular Mass Polypeptide-7 212 2.4 Kinases 214 2.4.1 Transforming Growth Factor Beta-Activating Kinase 214 2.4.2 Bruton’s Tyrosine Kinase 215 2.4.3 IL-2-Inducible T-Cell Kinase 216 2.4.4 Janus Kinase 3 218 3. Conclusion 220 Sami Osman and Michael Friedman
Chapter 12	The Evolution of Selective FGFR4 Inhibitors for FGF19-Driven Malignancies The Evolution of Selective FGFR4 Inhibitors for FGF19-Driven Malignancies 1. Introduction 229 2. FGFR4 Inhibitors 232 2.1 BLU-554 232 2.2 FGF401 234 2.3 H3B-6527 235 2.4 INCB062079 236 2.5 Pre-Clinical FGFR4 Inhibitors 237 2.6 Pan-FGFR Strategies 238 3. Future Directions and Conclusions 240 Joseph L. Kim, Chandra Miduturu, Megan A. Hatlen, Klaus P. Hoeflich, and Timothy Guzi
Chapter 13	Isoform-Selective Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancer Isoform-Selective Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancer 1. Introduction 245 2. Chemistry: Recent Inhibitors 247 2.1 HDAC1,2-Selective Inhibitors 247 2.2 Class IIa-Selective Inhibitors 248 2.3 HDAC3-Selective Inhibitors 249 2.4 HDAC6-Selective Inhibitors 251 2.5 HDAC8-Selective Inhibitors 253 2.6 Dual-Acting Inhibitors 255 3. HDAC Inhibitor Binding: Kinetics and Residence Time 256 4. Conclusions 259 Charles A. Blum and Matthew B. Jarpe
Chapter 14	Emerging Non-Canonical Small-Molecule Inhibitors of Androgen Receptor (AR) and AR Interactome Partners for the Treatment of Castrate-Resistant Prostate Cancer Emerging Non-Canonical Small-Molecule Inhibitors of Androgen Receptor (AR) and AR Interactome Partners for the Treatment of Castrate-Resistant Prostate Cancer 1. Introduction 268 2. Non-Canonical Small-Molecule Inhibitors of AR 271 2.1 Direct AR PROTAC Degraders 271 2.2 N-Terminal Domain (NTD) Small-Molecule Binders 271 2.3 DNA-Binding Domain (DBD) Small-Molecule Binders 274 3. Androgen Receptor Mutants—Targeted by Non-Steroidal AR Antagonists 275 3.1 AR Phenylalanine 876 to Leucine (AR-F876L) Mutation 276 3.2 AR Threonine 877 to Alanine (AR-T877A) Mutation 277 4. Small-Molecule Inhibitors of the AR Interactome 278 4.1 E26 Transformation-Specific (ETS) Family Inhibitors 278 4.2 AR Coregulator Binding Inhibitors 279 5. Conclusion 282 David B. Freeman, André Richters, Marius S. Pop, Nicholas B. Struntz, and Angela N. Koehler
Chapter 15	Recent Trends in Malaria Research Recent Trends in Malaria Research 1. Introduction 293 2. Current Chemotherapeutic Options 294 3. New Targets 296 4. New Drugs 298 4.1 Phenylalanine-Based Antimalarial Agents 299 4.2 Artemisinin-Based Antimalarial Agents 300 4.3 Aromatic Heterocycle-Based Antimalarial Agents 303 5. Conclusions 307 Christoph Boss and Sergio Wittlin
Chapter 16	Advances in Antifungal Drug Development Advances in Antifungal Drug Development 1. Introduction 314 2. Current Drug Classes 315 2.1 Agents for Superficial Infections 317 2.1.1 Oral Agents 317 2.1.2 Topical Agents 317 2.2 Agents for Systemic Mycoses 318 3. Old Dogs with New Tricks 318 3.1 Polyenes 319 3.2 Azoles 320 3.3 Echinocandins 321 4. Novel Targets and New Agents 322 4.1 Novel β-1,3-Glucan Synthase Inhibitors 322 4.1.1 Enfumafungin 322 4.1.2 Piperazinyl-Pyridazinones 322 4.2 IPC Synthase Inhibitors 323 4.3 Gwt1 Inhibitors 323 4.4 Pyrimidine Biosynthesis Inhibitors 324 4.4.1 Dihydroorotate Dehydrogenase (DHODH) Inhibitors 324 4.4.2 Dihydrofolate Reductase (DHFR) Inhibitors 324 4.5 Siderophores 325 4.6 Mitochondrial Targets 326 4.7 Histone Deacetylase Inhibitors 326 4.8 Peptide-Based Antifungals 326 5. Immunotherapeutics 327 5.1 Vaccines 327 5.2 Monoclonal Antibodies 328 5.3 Bifunctional Molecules 328 6. Conclusions 329 James M. Balkovec
Chapter 17	Recent Progress on Small-Molecule Influenze Virus Inhibitors Recent Progress on Small-Molecule Influenze Virus Inhibitors 1. Introduction 339 2. Current SOC: M2 Ion Channel and Neuraminidase Inhibitors 340 3. Polymerase Inhibitors 341 3.1 Broad Spectrum Polymerase Chain Inhibitors 341 3.2 PB1 Polymerase Inhibitors 342 3.3 PB2 Cap-Binding Inhibitors 342 3.4 PA Endonuclease Inhibitors 343 4. PA_c-PB1_N Protein-Protein Interaction Inhibitors 345 5. Nucleoprotein (NP) Inhibitors 346 6. Conclusions and Outlook 346 Michael P. Clark and Paul S. Charifson
Chapter 18	Therapeutic Potential of Alpha V Integrin Antagonists in TGFβ-Driven Disease Therapeutic Potential of Alpha V Integrin Antagonists in TGFβ-Driven Disease 1. Introduction 353 2. Potential Utility of Integrin Antagonists in the Treatment of TGF-β-Dependent Diseases 355 2.1 Disease Biology 355 2.2 Mechanism 355 2.3 Integrin Receptor Expression and Localization 356 2.4 Disease Biology, Relevant Models 356 3. Structure of αv Integrins and Relationship to Function in TGF-β Signaling 357 3.1 Integrin Conformational States and Affinity Regulation 357 3.2 Structural Basis for αvβ6-Mediated Pro-TGFβ Activation 361 3.3 Implications for Mechanism of Action and Ligand Design 364 4. Identification of Novel Integrin Antagonists 365 4.1 Overview of Pharmacophore and its Implications for Compound Properties 365 4.2 Review of Hit-Seeking Approaches to RGD Ligand Mimetics 368 5. Conclusions and Future Outlook 371 James E. Dowling, Fu-Yang Lin, Blaise Lippa, and Dawn Troast
Chapter 19	Therapeutic Applications of Nanobodies Therapeutic Applications of Nanobodies 1. Introduction 375 2. Structure and Production of Nanobodies 377 3. Types of Nanobodies 379 4. Therapeutic Applications of Nanobodies 380 4.1 Cancer 380 4.2 Neurological Diseases 383 4.3 Inflammation and Autoimmune Diseases 385 4.4 Infectious Diseases 387 4.5 Hematological Diseases 389 4.6 Respiratory Diseases 390 5. Conclusions 390 Srinivasa Karra and Sean McKenna
Chapter 20	HIV Integrase Inhibitors: Biochemical, QSAR, and Docking Studies HIV Integrase Inhibitors: Biochemical, QSAR, and Docking Studies 1. Introduction 397 2. Biology of Integrase 399 2.1 Mechanism of HIV Integrase 399 2.2 HIV-1 Integrase: Function and Structure 400 2.2.1 Theoretical Study 401 3. HIV Integrase Biochemical Assay 402 4. Development of Integrase Inhibitors 403 4.1 Early Inhibitors 403 4.2 Clinically Approved HIV-I Integrase Inhibitors: SAR 403 4.3 First-Generation Clinically Approved Integrase Inhibitors 406 4.3.1 Molecular Mechanisms of First-Generation Integrase Inhibitors 407 4.4 Second-Generation Clinically Approved Integrase Inhibitors 408 4.5 Newly Approved and Investigational Integrase Inhibitors 409 5. Conclusion 411 Omobolanle Janet Jesumoroti, Rosalyn Klein, and Paul Watts
Chapter 21	Physical Chemical Properties for Drug Design in Beyond Rule-of-Five Chemical Space Physical Chemical Properties for Drug Design in Beyond Rule-of-Five Chemical Space 1. Introduction 421 2. Physicochemical Properties Useful for Characterization of Large Molecules 423 2.1 Lipophilicity 424 2.2 Molecular Conformations, Intramolecular Hydrogen Bonding 426 2.3 Polarity, Hydrogen Bond Donors and Acceptors 426 2.4 Molecular Size 428 3. Chameleonic Properties of Beyond Rule-of-Five Drugs 429 4. Effect of Conformational Flexibility on Permeability and Bioavailability 430 5. Permeability Measurement and Prediction 432 6. Natural Products Have a Special Place Among Beyond Rule-Of-Five Drugs 433 7. Physicochemical Descriptors for Oral Bioavailability 434 8. Conclusions 435 Marina Shalaeva, Gilles Goetz, and Laurence Philippe
Chapter 22	Drug Metabolism and Pharmacokinetics Perspectives for Covalent Inhibitor Drug Development Drug Metabolism and Pharmacokinetics Perspectives for Covalent Inhibitor Drug Development 1. Introduction 441 2. Absorption and Distribution 445 3. Metabolic Stability and Biotransformation 446 4. Clearance 449 5. Human PK and Dose Prediction 449 6. PK/PD 451 6.1 In Vitro Potency and Target Occupancy 451 6.2 Drug T_1/2vs. Target T_1/2 452 6.3 Duration of Inhibition and Dosing Frequency 453 6.4 PK/PD Mathematical Models 454 7. Conclusions 456 Richard Zang, Shuguang Ma, and Matthew Wright
Chapter 23	Development of Small-Molecule Inhibitors of Monoacylglycerol Lipase for the Treatment of Neurologic Diseases Development of Small-Molecule Inhibitors of Monoacylglycerol Lipase for the Treatment of Neurologic Diseases 1. Introduction 463 2. Irreversible MGLL Inhibitors 465 2.1 Irreversible MGLL Inhibitors in Recent Peer-Reviewed Literature 465 2.2 Irreversible MGLL inhibitors in Recent Patent Literature 472 3. Reversible MGLL Inhibitors 473 3.1 Reversible MGLL Inhibitors in Recent Peer-Reviewed Literature 473 3.2 Reversible MGLL Inhibitors in Recent Patent Literature 475 4. Conclusions 476 John J.M. Wiener, Justin S. Cisar, Daniel J. Buzard, Olivia D. Weber, and Cheryl A. Grice
Chapter 24	Recent Advances in Small-Molecule TLR7 Agonists for Drug Discovery Recent Advances in Small-Molecule TLR7 Agonists for Drug Discovery 1. Introduction to the Toll-Like Receptors (TLRs) 481 1.1 TLR7 as a Key Molecular Target for Drug Discovery 483 1.2 The Development of Small-Molecule TLR7 Agonists 484 2. Inhaled Delivery Approaches Targeting Allergic Respiratory Diseases 486 2.1 Soft-Drug Approach with AZD8848 (9) 487 2.2 8-Oxoadenine GSK2245035 (11) 488 3. Oral Delivery Approaches Targeting Hepatitis 489 3.1 Pteridinone GS-9620 (Vesatolimod, 13) 490 3.2 Pyrrolo[3,2-d]pyrimidine (16) TLR7 Agonist 492 4. Vaccine Adjuvant Approach by Adsorption of TLR7 Agonists onto Aluminum Hydroxide 493 4.1 Benzonapthyridine (BZN)-based TLR7a as a Vaccine Adjuvant 493 4.2 Preclinical Evaluations for Meningitis C, Staph and Pertussis 494 5. Intratumoral Delivery Approaches for Cancer Immunotherapy 495 5.1 Phospholipid TLR7a 1V270 (25) 495 5.2 Lipid-Containing Imidazoquinoline MEDI9197 (26) 496 6. The Relationship Between TLR7 and TLR8 Receptors 497 6.1 Representative Dual TLR7 and TLR8 Agonists 498 7. Summary and Outlook 500 Alex Cortez and Porino Va
Chapter 25	Case History: Orkambi® (Ivacaftor/Lumacaftor), for the Treatment of Cystic Fibrosis Patients who are Homozygous for the F508del CFTR Mutation Case History: Orkambi® (Ivacaftor/Lumacaftor), for the Treatment of Cystic Fibrosis Patients who are Homozygous for the F508del CFTR Mutation 1. Introduction 509 2. Medicinal Chemistry Efforts That Led to the Discovery of Lumacaftor 511 2.1 Hit-to-Lead Efforts 512 2.2 Lead Optimization 514 3. In Vitro Pharmacology 516 4. Clinical Studies 518 5. Conclusion 520 Sabine Hadida, Fred Van Goor, Paul Negulescu, and Peter D.J. Grootenhuis
Chapter 26	Case History: IDHIFA® (Enasidenib), a First-in-Class Selective IDH2 Inhibitor for the Treatment of Acute Myeloid Leukemia Case History: IDHIFA® (Enasidenib), a First-in-Class Selective IDH2 Inhibitor for the Treatment of Acute Myeloid Leukemia 1. Introduction 525 2. Biological Relevance of Mutated IDH in AML 526 3. Discovery of Enasidenib 527 3.1 Hit-to-Lead Identification 527 3.2 Lead Optimization 529 4. Preclinical Characterization of Enasidenib 532 4.1 DMPK Properties of Enasidenib 532 4.2 Activity in U87MG mIDH2^R140Q Tumor Xenograft Model 533 4.3 Activity in Primary Human AML Xenograft Models 534 5. Clinical Profile 535 6. Conclusion 537 Zenon D. Konteatis and Zhihua Sui
Chapter 27	Case History: Curing Genotype 1-6 Hepatitis C: Velpatasvir, the NS5A Inhibitor in Epclusa® and Vosevi® Case History: Curing Genotype 1-6 Hepatitis C: Velpatasvir, the NS5A Inhibitor in Epclusa® and Vosevi® 1. Introduction 541 2. Genetic Diversity of Hepatitis C Virus (HCV) 544 3. Structure-Activity Relationships 546 4. Velpatasvir (VEL) 550 5. Velpatasvir In Vitro and Clinical Antiviral Activity 555 6. Curing GT1-6 HCV with VEL in Combination: Epclusa® and Vosevi® 558 7. Beyond Cure: HCV Elimination 562 8. Conclusion 563 John O. Link
Chapter 28	New Chemical Entities Entering Phase III Trials in 2017 Adam J. Schrier, Nathan E. Wright, Gregory T. Notte, and Amy S. Lee
Chapter 29	To Market, To Market--2017 To Market, To Market--2017 1. Abemaciclib (anticancer) 595 2. Acalabrutinib (anticancer) 597 3. Avelumab (anticancer) 599 4. Baricitinib (rheumatoid arthritis) 601 5. Benralizumab (asthma) 604 6. Benznidazole (antibacterial) 606 7. Betrixaban (venous thromboembolism) 608 8. Brigatinib (anticancer) 610 9. Copanlisib (anticancer) 612 10. Delafloxacin (antibacterial) 614 11. Deutetrabenazine (Huntington’s disease) 617 12. Dupilumab (atopic dermatitis) 619 13. Durvalumab (anticancer) 620 14. Elsulfavirine (antiviral) 622 15. Emicizumab (hemophilia) 624 16. Enasidenib (anticancer) 627 17. Ertugliflozin (antidiabetic) 628 18. Glecaprevir (antiviral) 630 19. Guselkumab (psoriasis) 632 20. Inotuzumab ozogamicin (anticancer) 634 21. Latanoprostene bunod (glaucoma) 637 22. Letermovir (antiviral) 640 23. Macimorelin (growth hormone deficiency) 641 24. Midostaurin (anticancer) 643 25. Naldemedine (opioid-induced constipation) 645 26. Neratinib (anticancer) 647 27. Netarsudil (glaucoma) 649 28. Niraparib (anticancer) 651 29. Ocrelizumab (multiple sclerosis) 653 30. Pemafibrate (dyslipidemia) 655 31. Pibrentasvir (antiviral) 657 32. Ribociclib (anticancer) 660 33. Sarilumab (antirheumatic) 662 34. Secnidazole (antibacterial) 664 35. Telotristat ethyl (carcinoid syndrome diarrhea) 665 36. Tivozanib (anticancer) 668 37. Vaborbactam (antibacterial) 669 38. Valbenazine (tardive dyskinesia) 672 39. Voxilaprevir (antiviral) 675 Catherine A. Bolger, Joseph E. Carpenter, T.G. Murali Dhar, Achal Pashine, Peter S. Dragovich, James H. Cook, Eric P. Gillis, Kevin M. Peese, and J. Robert Merritt

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Reviews: 2018 Medicinal Chemistry Reviews

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