Novel Bicyclic Piperazine Derivatives of Triazolotriazine and Triazolopyrimidines as Highly Potent and Selective Adenosine A2AReceptor Antagonists

Peng, Hairuo; Kumaravel, Gnanasambandam; Yao, Gang; Li, Sha; Wang, Joy; Vlijmen, Herman van; Bohnert, Tonika; Huang, Carol; Vu, Chi B.; Ensinger, Carol L.; Chang, Hexi; Engber, Thomas M.; Whalley, Eric T.; Petter, Russell C.

doi:10.1021/jm0494321

Cited by 66 publications

(35 citation statements)

References 17 publications

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“…T-62 has entered Phase I clinical trials as a treatment for neuropathic pain. 123,124 , and other A 2A AR antagonists, such as V2006 (a derivative of the antimalarial drug mefloquine), are in development [124][125][126] . V2006, which is beginning Phase II clinical trials, is well tolerated in high doses, and its pharmacokinetic properties suggest that it should be suitable for daily dosing.…”

Section: Painmentioning

confidence: 99%

Adenosine receptors as therapeutic targets

Jacobson

Gao

2006

Nat Rev Drug Discov

1,292

1,361

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Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer.

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Section: Painmentioning

confidence: 99%

Adenosine receptors as therapeutic targets

Jacobson

Gao

2006

Nat Rev Drug Discov

1,292

1,361

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“…An alternate sequence is also possible and cannot be excluded [17] (Pathway 2), which is the initial formation of an enamine by reaction of aminoazole with respective 1,3-carbonyl followed by cyclocondensation. The third alternative involving the formation of arylidene derivatives as intermediates requires the presence of a strong base [18] and is most likely not possible for the case described herein.…”

Section: Resultsmentioning

confidence: 99%

An Expeditious Synthesis of 1,2,4-Triazolo[1,5-a]Pyrimidine

Shah

Rojivadiya

2015

ILCPA

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A simple, efficient, and diversity oriented synthesis of library of 1,2,4-triazolo [1,5-a]pyrimidine was undertaken using 5-amino,1,2,4-triazole as a building block. The synthesized analogues were fully characterized by known spectroscopic techniques like FT-IR, 1 H NMR, 13 C NMR, and mass spectroscopy. INTRODUCTIONOne-pot multi-component reactions ( Thus in view of finding novel analogues of triazole[1,5-a]pyrimidine with potential biological activities, we set upon a synthetic program involving 5-amino,1,2,4-triazole as building block. Although different strategies have been employed for the synthesis of these compounds, [11][12][13][14][15] these methods suffer from drawbacks such as long reaction times, cumbersome isolation of the products and harsh reaction conditions. Herein, we report a facile and efficient multi-component synthesis of 1,2,4-triazolo[1,5-a]pyrimidine in excellent yields from 3-amino-1,2,4-triazole, aldehydes and ethyl 3-oxo hexanoate respectively by simple fusion followed by adding catalytic amount of dimethylformamide (Scheme 1). Synthesis of fifteen novel analogues of 1,2,4-triazolo[1,5-a]pyrimidines containing an appropriate 1,3-bifunctional synthon has been undertaken. The structures of all the newly synthesized compounds were elucidated by FT-IR, mass spectra, 1 H NMR, 13C NMR and elemental analysis.

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“…An alternate sequence is also possible and cannot be excluded [19], which is the initial formation of an enamine by reaction of aminoazole with respective 1,3-carbonyl followed by cyclocondensation. The third alternative involving the formation of arylidene derivatives as intermediates requires the presence of a strong base [20] and is most likely not possible for the case described herein.…”

Section: Resultsmentioning

confidence: 99%