The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life
Journal Article
·
· Bioorg. Med. Chem. Lett.
- Pfizer
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{sub 1/2} = 360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t{sub 1/2} = 34 h.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- INDUSTRY
- OSTI ID:
- 1025630
- Journal Information:
- Bioorg. Med. Chem. Lett., Vol. 20, Issue (23) ; 12, 2010
- Country of Publication:
- United States
- Language:
- ENGLISH
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