41259-67-0Relevant academic research and scientific papers
Orally active purine-based inhibitors of the heat shock protein 90
Biamonte, Marco A.,Shi, Jiandong,Hong, Kevin,Hurst, David C.,Zhang, Lin,Fan, Junhua,Busch, David J.,Karjian, Patricia L.,Maldonado, Angelica A.,Sensintaffar, John L.,Yang, Yong-Ching,Kamal, Adeela,Lough, Rachel E.,Lundgren, Karen,Burrows, Francis J.,Timony, Gregg A.,Boehm, Marcus F.,Kasibhatla, Srinivas R.
, p. 817 - 828 (2007/10/03)
Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently
Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures
Dymock, Brian,Barril, Xavier,Beswick, Mandy,Collier, Adam,Davies, Nicholas,Drysdale, Martin,Fink, Alexandra,Fromont, Christophe,Hubbard, Roderick E.,Massey, Andrew,Surgenor, Allan,Wright, Lisa
, p. 325 - 328 (2007/10/03)
Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold
An efficient one-pot synthesis of 6-alkoxy-8,9-dialkylpurines via reaction of 5-amino-4-chloro-6-alkylaminopyrimidines with N,N-dimethylalkaneamides and alkoxide ions
Baraldi, Pier Giovanni,Broceta, Asier Unciti,Infantas, Maria Josè Pineda De Las,Mochun, Juan Josè Dìaz,Espinosa, Antonio,Romagnoli, Romeo
, p. 7607 - 7611 (2007/10/03)
The synthesis of a number of new 6-alkoxy-8,9-(disubstituted)purines has been accomplished by the cyclization of the corresponding intermediate 5-amino-4-chloro-6-(alkylamino)pyrimidines promoted by alkoxides and various N,N-dimethyl amides, where the latter act as solvent-reagents. By this three-component condensation reaction we are able to introduce an alkyl group in the 8 position of the purine ring with the concomitant nucleophilic replacement of the 6-chloro group with an alkoxy moiety.
6-(alkylamino)-9-alkylpurines. A new class of potential antipsychotic agents
Kelley, James L.,Morris Bullock,Krochmal, Mark P.,McLean, Ed W.,Linn, James A.,Durcan, Micheal J.,Cooper, Barrett R.
, p. 3207 - 3216 (2007/10/03)
A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)- 9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6- (cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H-purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure-activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.
