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

  • J Med Chem. 2024 Jul 11;67(13):10986-11002. doi: 10.1021/acs.jmedchem.4c00514.
Bart Kesteleyn  1 ,  Florence Herschke  1 ,  Nicolas Darville  1 ,  Bart Stoops  1 ,  Tom Jacobs  1 ,  Edgar Jacoby  1 ,  Paul Shaffer  2 ,  Lieve Lammens  1 ,  Dries Van Rompaey  1 ,  Kiran Matcha  1 ,  Carolina Martinez Lamenca  1 ,  Erwin Coesemans  1 ,  Geerwin Hache  1 ,  Serge Pieters  1 ,  Morgan Lecomte  1 ,  Lili Hu  1 ,  Samuel Demin  1 ,  Cynthia Milligan  2 ,  Pravien Abeywickrema  2 ,  Suzanne De Bruyn  1 ,  Joke Van Den Berg  1 ,  Nina Ysebaert  1 ,  Loeckie De Zwart  1 ,  Isabel Nájera  1 ,  Peter Rigaux  1 ,  Dirk Roymans  1 ,  Tim H M Jonckers  1
Affiliations
  • 1. Janssen Research & Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, Beerse 2340, Belgium.
  • 2. Janssen Research & Development, 1400 McKean Rd, Spring House, Pennsylvania 19477, United States.
PMID: 38932487 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.

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