2018 Medicinal Chemistry Reviews

Volume 53, Chapter 24

Recent Advances in Small-Molecule TLR7 Agonists for Drug Discovery

Alex Cortez and Porino Va

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

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