Spiro-Azetidine Oxindoles as Long-Acting Injectables for Pre-Exposure Prophylaxis against Respiratory Syncytial Virus Infections

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.