{Reference Type}: Journal Article
{Title}: Spiro-Azetidine Oxindoles as Long-Acting Injectables for Pre-Exposure Prophylaxis against Respiratory Syncytial Virus Infections.
{Author}: 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;Jonckers THM;
{Journal}: J Med Chem
{Volume}: 67
{Issue}: 13
{Year}: 2024 Jul 11
{Factor}: 8.039
{DOI}: 10.1021/acs.jmedchem.4c00514
{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.