1010701-24-2Relevant academic research and scientific papers
Third-generation immucillins: Syntheses and bioactivities of acyclic immucillin inhibitors of human purine nucleoside phosphorylase
Clinch, Keith,Evans, Gary B.,Frohlich, Richard F. G.,Furneaux, Richard H.,Kelly, Peter M.,Legentil, Laurent,Murkin, Andrew S.,Li, Lei,Schramm, Vern L.,Tyler, Peter C.,Woolhouse, Anthony D.
experimental part, p. 1126 - 1143 (2010/02/16)
ImmH (1) and DADMe-ImmH (2) are potent inhibitors of human purine nucleoside phoshorylase (PNP), developed by us and currently in clinical trials for the treatment of a variety of T-cell related diseases. Compounds 1 and 2 were used as templates for the design and synthesis of a series of acyclic immucillin analogues (8-38) in order to identify simplified alternatives to 1 and 2. SerMe-ImmG (8) and DATMe- ImmG (9) displayed the lowest inhibition constants of 2.1 and 3.4 pM, respectively, vs PNP. It was postulated that the flexible natures of 8 and 9 enabled them to adopt conformations resembling those of 1 and 2 within the active site of PNP and that the positioning of two hydroxyl groups was critical for picomolar activity. SerMe-ImmH (10, K d = 5.2 pM) was shown to be orally available in mice with a long biological residence time on blood PNP.
ACYCLIC AMINE INHIBITORS OF NUCLEOSIDE PHOSPHORYLASES AND HYDROLASES
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Page/Page column 31; 32, (2008/06/13)
The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and/or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.
