- Concise Xanthine Synthesis through a Double-Amidination Reaction of a 6-Chlorouracil with Amidines using Base-Metal Catalysis
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A new and concise route towards xanthines through a double-amidination reaction is described; consecutive intermolecular C?Cl and intramolecular oxidative C?H amidination. N-uracil amidines are obtained through SNAE on a 6-chlorouracil with amidines. Direct Cu-catalyzed oxidative C?H amidination on these N-uracil amidines yields polysubstituted xanthines. Sustainable oxidants, tBu2O2or O2, can be used in this oxidase-type reaction. The protocol allows for the introduction of N1, N3, N7, and C8 substituents during the xanthine-scaffold construction, thus avoiding post-functionalization steps. Both 6-chlorouracils and amidines are readily available commercially or through synthesis.
- Morel, Bénédicte,Franck, Philippe,Bidange, Johan,Sergeyev, Sergey,Smith, Dan A.,Moseley, Jonathan D.,Maes, Bert U. W.
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p. 624 - 628
(2017/02/15)
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- Dual inhibition of monoamine oxidase B and antagonism of the adenosine A2A receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues
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The adenosine A2A receptor has emerged as an attractive target for the treatment of Parkinson's disease (PD). Evidence suggests that antagonists of the A2A receptor (A2A antagonists) may be neuroprotective and may help to alleviate the symptoms of PD. We have reported recently that several members of the (E)-8-styrylcaffeine class of A2A antagonists also are potent inhibitors of monoamine oxidase B (MAO-B). Since MAO-B inhibitors are known to possess anti-parkinsonian properties, dual-target-directed drugs that block both MAO-B and A2A receptors may have enhanced value in the management of PD. In an attempt to explore this concept further we have prepared three additional classes of C-8 substituted caffeinyl analogues. The 8-phenyl- and 8-benzylcaffeinyl analogues exhibited relatively weak MAO-B inhibition potencies while selected (E,E)-8-(4-phenylbutadien-1-yl)caffeinyl analogues were found to be exceptionally potent reversible MAO-B inhibitors with enzyme-inhibitor dissociation constants (Ki values) ranging from 17 to 149 nM. Furthermore, these (E,E)-8-(4-phenylbutadien-1-yl)caffeines acted as potent A2A antagonists with Ki values ranging from 59 to 153 nM. We conclude that the (E,E)-8-(4-phenylbutadien-1-yl)caffeines are a promising candidate class of dual-acting compounds.
- Pretorius, Judey,Malan, Sarel F.,Castagnoli Jr., Neal,Bergh, Jacobus J.,Petzer, Jacobus P.
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p. 8676 - 8684
(2008/12/23)
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- A CONVERSION OF OXADIAZOLOPYRIMIDINE 1-OXIDES INTO PURINES
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Treatment of oxadiazolopyrimidine 1-oxides with amines led to the formation of the corresponding 8-substituted purine derivatives, along with other heterocyclic compounds in some cases.
- Yoneda, Fumio,Tachibana, Takako,Tanoue, Junko,Yano, Tetsumi,Sakuma, Yoshiharu
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p. 341 - 344
(2007/10/02)
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