- Projected Dose Optimization of Amino- And Hydroxypyrrolidine Purine PI3KδImmunomodulators
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The approvals of idelalisib and duvelisib have validated PI3Kδinhibitors for the treatment for hematological malignancies driven by the PI3K/AKT pathway. Our program led to the identification of structurally distinct heterocycloalkyl purine inhibitors wit
- Methot, Joey L.,Zhou, Hua,McGowan, Meredeth A.,Anthony, Neville John,Christopher, Matthew,Garcia, Yudith,Achab, Abdelghani,Lipford, Kathryn,Trotter, Benjamin Wesley,Altman, Michael D.,Fradera, Xavier,Lesburg, Charles A.,Li, Chaomin,Alves, Stephen,Chappell, Craig P.,Jain, Renu,Mangado, Ruban,Pinheiro, Elaine,Williams, Sybill M. G.,Goldenblatt, Peter,Hill, Armetta,Shaffer, Lynsey,Chen, Dapeng,Tong, Vincent,McLeod, Robbie L.,Lee, Hyun-Hee,Yu, Hongshi,Shah, Sanjiv,Katz, Jason D.
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p. 5137 - 5156
(2021/05/04)
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- New potent and selective A1 adenosine receptor antagonists as potential tools for the treatment of gastrointestinal diseases
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The synthesis of 9-alkyl substituted adenine derivatives presenting aromatic groups and cycloalkyl rings in 8- and N6-position, respectively, is reported. The compounds were tested with radioligand binding studies showing, in some cases, a low
- Lambertucci, Catia,Marucci, Gabriella,Dal Ben, Diego,Buccioni, Michela,Spinaci, Andrea,Kachler, Sonja,Klotz, Karl-Norbert,Volpini, Rosaria
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p. 199 - 213
(2018/04/05)
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- A One-Pot Synthesis of Highly Functionalized Purines
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Highly substituted purines were synthesized in good to high yields through a one-pot straightforward metal-free scalable method, using the Traube synthesis adapted to Vilsmeier-type reagents. From 5-amino-4-chloropyrimidines, new 9-aryl-substituted chloropurines and intermediates for peptide nucleic acid synthesis were prepared. Variant procedures allowing a rapid synthesis of ribonucleosides and 7-benzylpurine from 5-amidino-6-aminopyrimidines are also reported to illustrate the high potential of this versatile toolbox. This route appears to be particularly interesting in the field of nucleic acids for a direct and rapid access to various new 8-alkylpurine nucleosides.
- Zelli, Renaud,Zeinyeh, Wa?l,Haudecoeur, Romain,Alliot, Julien,Boucherle, Benjamin,Callebaut, Isabelle,Décout, Jean-Luc
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supporting information
p. 6360 - 6363
(2017/12/08)
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- PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA
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The instant invention provides compounds of formula I which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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Page/Page column 175
(2014/06/11)
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- 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
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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.
- Baraldi, Pier Giovanni,Broceta, Asier Unciti,Infantas, Maria Josè Pineda De Las,Mochun, Juan Josè Dìaz,Espinosa, Antonio,Romagnoli, Romeo
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p. 7607 - 7611
(2007/10/03)
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- 6-(alkylamino)-9-alkylpurines. A new class of potential antipsychotic agents
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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.
- Kelley, James L.,Morris Bullock,Krochmal, Mark P.,McLean, Ed W.,Linn, James A.,Durcan, Micheal J.,Cooper, Barrett R.
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p. 3207 - 3216
(2007/10/03)
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