1. Spiro-Azetidine Oxindoles as Long-Acting Injectables for Pre-Exposure Prophylaxis against Respiratory Syncytial Virus Infections.
- Author
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Kesteleyn B, Herschke F, Darville N, Stoops B, Jacobs T, Jacoby E, Shaffer P, Lammens L, Van Rompaey D, Matcha K, Martinez Lamenca C, Coesemans E, Hache G, Pieters S, Lecomte M, Hu L, Demin S, Milligan C, Abeywickrema P, De Bruyn S, Van Den Berg J, Ysebaert N, De Zwart L, Nájera I, Rigaux P, Roymans D, and Jonckers THM
- Subjects
- Humans, Animals, Pre-Exposure Prophylaxis methods, Injections, Intramuscular, Indoles chemistry, Indoles administration & dosage, Indoles pharmacology, Injections, Subcutaneous, Respiratory Syncytial Virus, Human drug effects, Virus Internalization drug effects, Respiratory Syncytial Virus Infections prevention & control, Respiratory Syncytial Virus Infections drug therapy, Oxindoles chemistry, Oxindoles pharmacology, Spiro Compounds chemistry, Spiro Compounds pharmacology, Spiro Compounds pharmacokinetics, Spiro Compounds administration & dosage, Antiviral Agents pharmacology, Antiviral Agents chemistry, Antiviral Agents administration & dosage, Azetidines chemistry, Azetidines pharmacology, Azetidines administration & dosage, Azetidines pharmacokinetics
- Abstract
Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants, the elderly, and immune-compromised patients. While a half-life extended monoclonal antibody and 2 vaccines have recently been approved for infants and the elderly, respectively, options to prevent disease in immune-compromised patients are still needed. Here, we describe spiro-azetidine oxindoles as small molecule RSV entry inhibitors displaying favorable potency, developability attributes, and long-acting PK when injected as an aqueous suspension, suggesting their potential to prevent complications following RSV infection over a period of 3 to 6 months with 1 or 2 long-acting intramuscular (IM) or subcutaneous (SC) injections in these immune-compromised patients.
- Published
- 2024
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