Purine scaffold

One type of synthesis was described by Ding et al.15 (Fig. 1). A drawback to this approach is the low reactivity of a polymer-bound amine. This problem may be alleviated to some extent by activating the heterocycle with ammonium salts16 and by the choice of linker. Mainly acid-labile indole24 (28) and PAL linkers25 (26) have been employed. The possibility of activating C2 by acylation of N626 of the purine scaffold was not... 

Mitsunobu Reaction for Endocyclic N9-Alkylation on Purine Scaffold (60) (Fig. 10).15 This is described later in the section dedicated to Mitsunobu reactions. 

Mitsunobu Reaction for Exocyclic N2-Alkylation on a Purine Scaffold (Fig. 16).47 2,6-Di-tert-butyl-4-methylpyridine (1.54 g, 7.5 mmol, 0.3 M) is added to freshly distilled CH2C12 (25 ml) at 0° under N2. To this solution is added trifluoroacetic anhydride (706 pi, 5.0 mmol, 0.2 M) and the mixture is stirred for 5-10 min. The solution is then transferred to the resin 83 and the flask is vortexed and vented several times to relieve pressure. The flask is shaken for 6-12 h after which the solvent is removed and the resin washed with dry CH2C12 (5 x 25 ml) with vortexing between each rinse. The resulting resin 84 is dried. 

Chiosis, G., Lucas, B. et al. 2003. Development of purine-scaffold small molecule inhibitors of Hsp90. Curr. 

Raynaud and co-workers recently reported the optimization of inhibitors of cyclin-dependent kinase-2 (CDK-2), based on a purine scaffold (Scheme 7). The synthesis... 

He H, Zatorska D, Kim J, Aguirre J, Llauger L, She Y, Wu N, Immormino RM, Gewirth DT, Chiosis G (2006) Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J Med Chem 49 381-390... 

Chiosis G, Lucas B, Shtil A, Huezo H, Rosen N (2002) Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase. Bioorg Med Chem 10 3555-3564... 

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