Download MendeleyThe novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life.
Wang, J.L., Limburg, D., Graneto, M.J., Springer, J., Hamper, J.R., Liao, S., Pawlitz, J.L., Kurumbail, R.G., Maziasz, T., Talley, J.J., Kiefer, J.R., Carter, J.(2010) Bioorg Med Chem Lett 20: 7159-7163
- PubMed: 20709553
- DOI: https://doi.org/10.1016/j.bmcl.2010.07.054
- Primary Citation of Related Structures:
3LN0, 3LN1, 3MQE, 3NTG - PubMed Abstract:
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34 h.
Organizational Affiliation:
Pfizer Global Research and Development, Chesterfield, MO 63017, USA. [email protected]
