Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 18, Pages 5880-5884Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm800792b
Keywords
-
Categories
Funding
- NIH [GM41916]
- New Zealand Foundation for Research, Science Technology
Ask authors/readers for more resources
The potent immucillin purine nucleoside phosphorylase (PNP) inhibitors F-DADMe-ImmH [(3S,4S)-3], and [(3R,4R)-3] are synthesized in seven steps. Cycloaddition to a fluoroalkene and an enzymic resolution are the key features of the construction of the fluoropyrrolidines 11, from which the immucillins are assembled by use of a three-component Mannich reaction. Slow-onset binding constants (K(i)*) for [(3S,4S)-3] and [(3R,4R)-3] with human PNP are 0.032 and 1.82 nM, respectively. F-DADMe-ImmH [(3S,4S)-3] exhibits oral availability in mice at doses as low as 0.2 mg/kg.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available