Of pyrazolopyrimidines

A synthesis of pyrazolopyrimidines from methoxybutenone has been patented (99W054333). 

PCI-32765 1 is the only Btk inhibitor which has been reported to have advanced to clinical trials [40]. Modeling of pyrazolopyrimidine 2 suggested that replacement of the cyclopentyl moiety could position an electrophilic group in proximity to Cys481, and subsequent optimization led to 1 [41]. Compound 1 inhibits Btk with an IC50 of 0.8 nM, and covalent binding to Btk was confirmed by mass spectrometry and washout experiments. In the Ramos B-cell line, 1 inhibits BCR-induced calcium... 

The interesting biological activities reported for pyrazolopyrimidines have stimulated chemists to develop the chemistry of this class of compounds. In the last 20 years, an enormous number of papers and patents dealing with the chemistry or biological activity of pyrazolopyrimidines have been reported. However this article appears to be the first survey of the chemistry and biological activity of this class of compounds. 

STE = 0.64). The same cross-validation protocol was carried out in the case of Pyrazolopyrimidine series obtaining the following correlation coefficients r2on. cv = 0.78 (STE =... 

Many reports of fused-pyrazole heterocycles have been published. A high throughput synthesis of pyrazolopyrimidines has been achieved by copper(I)-catalyzed cyclizations <05H(65)1821>. A simple synthesis of 6-phenylpyrano[2,3-c]pyrazol-4(lf/)-ones has been reported <05S2583>. A solvent-free, one-pot synthesis of pyrano[2,3-c]pyrazole derivatives in the presence of potassium fluoride and grinding has been disclosed <05SC2509>. Reactions of... 

The amino-iminophosphorane (16.2) is cyclized by heating with an isocyanate. A closely related iminophosphorane (16.3) reacts with an isocyanate in unheated dichloromethane to form a new fused 2-iminopyrimidine. When the imino is replaced with a hydrazono function (R = ArNH), a similar 2-iminopyrimidine ring is produced. The chemistry of pyrazolopyrimidines has been reviewed [3360]. 

Heating the oxime of 2-aminobenzophenone with ethyl orthoformate gives quinazoline A -oxide. A pyrazolopyrimidine Af-oxide has been similarly synthesized the chemistry of pyrazolopyrimidines has been reviewed [33601. 

A remarkable synthesis of pyrazolopyrimidines (169) involves the reaction of the azines (167) with nitriles the intermediate 1 2 molecular adducts... 

There are many methods for the synthesis of pyrazolopyrimidines (02SOS(12)613, 84CHEC(5)305, 96CHEC-II(8)365, 08CHEC-III(11)551). With diethyl l-dimethylamino-3-oxobut-l-ene-2,4-dicarboxylate (2) and aminoguanidine, first a substitution intermediate 42 is formed, which cyclizes into pyrazole 43, followed by cyclization into the bicyclic 7-amino-2-ethoxycarbonyl-lH,2H-pyrazolo[2,3-c]pyrimidin-5-one (44). The intermediates 42 and 43 were not isolated (08ACSil019) (Scheme 16). 

Looker DL, Marr JJ, Berens RL. Mechanisms of action of pyrazolopyrimidines in Leishmania donovani. J Biol Chem 1986 261(20) 9412-9415. 

The left panel indicates normal purine salvage pathways. The panel on the right summarizes the metabolism of pyrazolopyrimidine analogues. The X in the 4 position indicates the possibility of substituting the following groups -OH, -SH, -NH2. The pyrazolopyrimidine abbreviations are given in the text. The enzymes which mediate the pyrazolopyrimidine conversions are those listed in the left panel. 

The approach to nucleoside synthesis developed by Ogura et al. (Heterocycles, 911, 8, 125, and earlier references), which involved the reaction of glycosyl isothiocyanates with substituted hydrazines to give thiosemicarbazides which were cyclized with NBS, and finally desulphurized to give the required heterocycle, has now been applied to the synthesis of pyrazolopyrimidine nucleosides derived from D-glucopyranosyl, D-arabinopyranosyl, and d-ribofuranosyl isothiocyanates. Syntheses of nucleoside analogues from reactions of glycosyl isothiocyanates with amino-acids, enamines, and diamines have been summarized. ... 

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