Kilogram-Scale Synthesis and Impurity Profiling of a COPD Candidate <b>LY104</b>: Optimization of Salt Forms for Enhanced Purity and Pharmaceutical Potential
This study describes a synthetic route to access LY104, a structurally novel compound investigated for the treatment of chronic obstructive pulmonary disease (COPD). Our approach to LY104 encompasses (i) a concise and efficient synthetic strategy for this COPD candidate and (ii) a scalable process with structural characterization of related impurities. The synthesis of LY104 was accomplished in four steps, during which three key impurity structures were identified. Through careful optimization of the chemical process, LY104 acetate salt was consistently obtained in a high purity (>99.85%) for pharmacological studies.
Authors
- Kaile Li (ORCID: https://orcid.org/0009-0007-0845-2799)
- Guanhua Du (ORCID: https://orcid.org/0000-0002-6896-0847)
- Xiaokun Liu (ORCID: https://orcid.org/0000-0002-8636-9743)
- De Wang (ORCID: https://orcid.org/0000-0002-3737-6621)
- Shengbiao Wan (ORCID: https://orcid.org/0000-0002-0842-572X)
- Ping Zhang (ORCID: https://orcid.org/0000-0001-9163-6191)
- Jilong Zhang (ORCID: https://orcid.org/0000-0002-5813-0452)
- Jiejie Hao (ORCID: https://orcid.org/0000-0001-6997-547X)
- Wanli Meng
Institutions
- Marine Biomedical Research Institute of Qingdao (CN)
- Ocean University of China (CN)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2025-06-16
- DOI
- https://doi.org/10.1021/acs.oprd.5c00123
- Primary Topic
- Inhalation and Respiratory Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00