Understanding and controlling the formation of an impurity during the development of muraglitazar, a PPAR dual agonist

Organic Process Research and Development

Volumn 14, Issue 1, 2010, Pages 238-241

  Ye, Qingmei ^a   Huang, Yande ^a   Rusowicz, Andrew ^a   Palaniswamy, Venkatapuram A ^a   Raglione, Thomas V ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77149161093     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op9002104     Document Type: Article

References (11)

1. Malinowski, J. M.; Bolesta, S. Clin. Ther. 2000, 22, 1151-1167.
2. Gillies, P. S.; Dunn, C. J. Drugs 2000, 60, 333-334.
3. Nomura, M.; Kinoshita, S.; Satoh, H.; Maeda, T.; Murakami, K.; Tsunoda, M.; Miyachi, H.; Awano, K. Bioorg. Med. Chem. Lett. 1999, 9, 533-538.
4. Mclntyre, J. A.; Castaner, J. A.; Bayes, M. Drugs Future 2003, 28, 959-965.
5. Sorbera, L. A.; Castaner, J.; Leeson, P. A.; Martin, L. Drugs Future 2001, 26, 354-363.
6. International Conference on Harmonisation (ICH) Guidelines, Q3A(R), Impurities in New Drug Substances (Revised Guideline); U.S. Department of Health and Human Services, Food and Drug Administration: Washington, DC, 2008.
7. Rusowicz, A.; Lane, G. C.; Saindane, M.; Chung, H. J.; Malley, M. F. PCT Int. Appl. WO 2005/113521, 2005.
8. 13C NMR chemical shift assignments of impurity A are shown in Table 1 in the Supporting Information.
9. 13C and DEPT NMR spectra of impurity D are shown in the Supporting Information.
10. 13C and DEPT NMR spectra of impurity D are shown in the Supporting Information.
11. Starting material, 4-hydroxybenzaldehyde, was supplied by multiple vendors. Some of the batches were free of the minor contaminant, impurity D. Therefore, we believe if we set an appropriate specification on impurity D and engage the vendors to meet the specification, the impurity A in API can be effectively controlled.