✦ LIBER ✦

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life

✍ Scribed by Jane L. Wang; David Limburg; Matthew J. Graneto; John Springer; Joseph Rogier Bruce Hamper; Subo Liao; Jennifer L. Pawlitz; Ravi G. Kurumbail; Timothy Maziasz; John J. Talley; James R. Kiefer; Jeffery Carter

Book ID: 104004660
Publisher: Elsevier Science
Year: 2010
Tongue: English
Weight: 811 KB
Volume: 20
Category: Article
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2010.07.054

No coin nor oath required. For personal study only.

✦ Synopsis

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.

📜 SIMILAR VOLUMES

The novel benzopyran class of selective

The novel benzopyran class of selective cyclooxygenase-2 inhibitors-part I: The first clinical candidate

✍ Jane L. Wang; Jeffery Carter; James R. Kiefer; Ravi G. Kurumbail; Jennifer L. Pa 📂 Article 📅 2010 🏛 Elsevier Science 🌐 English ⚖ 660 KB

The novel benzopyran class of selective

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part III: The three microdose candidates

✍ Jane L. Wang; Karl Aston; David Limburg; Cindy Ludwig; Ann E. Hallinan; Francis 📂 Article 📅 2010 🏛 Elsevier Science 🌐 English ⚖ 742 KB

ChemInform Abstract: The Novel Benzopyra

ChemInform Abstract: The Novel Benzopyran Class of Selective Cyclooxygenase-2- Inhibitors. Part 3. The Three Microdose Candidates.

✍ Jane L. Wang; et al. et al. 📂 Article 📅 2011 🏛 John Wiley and Sons ⚖ 24 KB 👁 1 views

Correction to Discovery of a Novel Class

Correction to Discovery of a Novel Class of Exquisitely Selective Mesenchymal-Epithelial Transition Factor (c-MET) Protein Kinase Inhibitors and Identification of the Clinical Candidate 2-(4-(1-(Quinolin-6-ylmethyl)-1 H -[1,2,3]triazolo[4,5- b ]pyrazin-6-yl)-1 H -pyrazol-1-yl)ethanol (PF-04217903) for the Treatment of Cancer

✍ Cui, J. Jean; McTigue, Michele; Nambu, Mitchell; Tran-Dubé, Michelle; Pairish, M 📂 Article 📅 2012 🏛 American Chemical Society 🌐 English ⚖ 124 KB

Discovery of a Novel Class of Phosphodie

Discovery of a Novel Class of Phosphodiesterase 10A Inhibitors and Identification of Clinical Candidate 2-[4-(1-Methyl-4-pyridin-4-yl-1 H -pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the Treatment of Schizophrenia † † Coordinates of the PDE10A crystal structures have been deposited in the Protein Data Bank for compound 1 (3HQW), 2 (3HQY), 3 (3HQW) and 9 (3HR1).

✍ Verhoest, Patrick R.; Chapin, Douglas S.; Corman, Michael; Fonseca, Kari; Harms, 📂 Article 📅 2009 🏛 American Chemical Society 🌐 English ⚖ 1015 KB