Exploring the Synthesis of Janssen's RSV-F Inhibitor Using ChemAIRS_EP03
Discovery of a Spiro-Azetidine Oxindole Sulfonamide as a Potent RSV Fusion Inhibitor: A Promising Therapeutic Candidate for Prophylactic Treatment
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in pediatric, geriatric, and immunocompromised populations. Researchers at Janssen Pharmaceuticals discovered a spiro-azetidine oxindole sulfonamide derivative, exhibiting potent inhibition of the RSV fusion protein. This small-molecule inhibitor represents a promising therapeutic candidate for the prophylactic treatment of RSV infections, addressing a significant unmet medical need.
References: https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c00514?ref=PDF
ChemAIRS Proposed Retrosynthetic Strategy for Spiro-Azetidine Oxindole Sulfonamide, a Potent RSV Fusion Inhibitor
The most concise route for the synthesis of this compound proposed by ChemAIRS (Scheme 1) closely resembles the method reported by Janssen. The procedure initiates with the preparation of two crucial intermediates: spiro-azetidine oxindole sulfonamide 3a and benzimidazole derivative 3b. These two intermediates (3a and 3b) are then coupled via a straightforward displacement reaction to produce the final API.
Scheme 1: ChemAIRS-Proposed Retrosynthetic Pathway for Spiro-Azetidine Oxindole Sulfonamide Mirrors Janssen's Reported Methodology
ChemAIRS-Identified Cost-Efficient Synthetic Route to Spiro-Azetidine Oxindole Sulfonamide
However, given the cost and availability issues of one of the starting materials (2b and 1b in Scheme 1), we explored an alternative synthetic route to achieve a more economical solution. We tasked the system with proposing a different synthesis method for 8a and 2b, as illustrated in Scheme 2. Compound 7b is synthesized through a four-step sequence, starting from the commercially affordable reagent 3a. A base-induced rearrangement of 5a yields 6a, which undergoes Boc-deprotection followed by an S-N coupling reaction to produce the desired sulfonamide 8a.
Scheme 2: ChemAIRS-Identified Cost-Efficient Synthetic Route to Spiro-Azetidine Oxindole Sulfonamide
Overall, ChemAIRS demonstrates its proficiency in generating a variety of viable synthetic pathways, providing users with the flexibility to customize the synthetic route according to their specific requirements.
Interested in exploring the capabilities of our Retrosynthesis module? Learn more here: ChemAIRS_Retrosynthesis