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Your search keyword '"Knight, Anthony"' showing total 6 results
Start Over Author "Knight, Anthony" Journal journal of medicinal chemistry
6 results on '"Knight, Anthony"'

3. Antagonists of the Human A2A Adenosine Receptor. 4. Design, Synthesis, and Preclinical Evaluation of 7-Aryltriazolo[4,5-d]pyrimidines

Author

Gillespie, Roger J., primary, Bamford, Samantha J., additional, Botting, Ruth, additional, Comer, Mike, additional, Denny, Sarah, additional, Gaur, Suneel, additional, Griffin, Michael, additional, Jordan, Allan M., additional, Knight, Anthony R., additional, Lerpiniere, Joanne, additional, Leonardi, Stefania, additional, Lightowler, Sean, additional, McAteer, Steven, additional, Merrett, Angela, additional, Misra, Anil, additional, Padfield, Antony, additional, Reece, Mark, additional, Saadi, Mona, additional, Selwood, Daniel L., additional, Stratton, Gemma C., additional, Surry, Dominic, additional, Todd, Richard, additional, Tong, Xin, additional, Ruston, Vicki, additional, Upton, Rebecca, additional, and Weiss, Scott M., additional

Published
2008
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6. Antagonists of the human A(2A) adenosine receptor. 4. Design, synthesis, and preclinical evaluation of 7-aryltriazolo[4,5-d]pyrimidines.

Author

Gillespie RJ, Bamford SJ, Botting R, Comer M, Denny S, Gaur S, Griffin M, Jordan AM, Knight AR, Lerpiniere J, Leonardi S, Lightowler S, McAteer S, Merrett A, Misra A, Padfield A, Reece M, Saadi M, Selwood DL, Stratton GC, Surry D, Todd R, Tong X, Ruston V, Upton R, and Weiss SM

Subjects
Amines chemistry, Animals, Azoles chemistry, Azoles therapeutic use, Drug Evaluation, Preclinical, Gait Disorders, Neurologic chemically induced, Gait Disorders, Neurologic drug therapy, Haloperidol pharmacology, Humans, Mice, Molecular Structure, Pyrimidines chemistry, Pyrimidines therapeutic use, Rats, Receptor, Adenosine A2A classification, Receptor, Adenosine A2A metabolism, Structure-Activity Relationship, Adenosine A2 Receptor Antagonists, Azoles chemical synthesis, Azoles pharmacology, Drug Design, Pyrimidines chemical synthesis, Pyrimidines pharmacology
Abstract

Antagonism of the human A(2A) receptor has been implicated as a point of therapeutic intervention in the alleviation of the symptoms associated with Parkinson's disease. This is thought to occur, at least in part, by increasing the sensitivity of the dopaminergic neurons to the residual, depleted levels of striatal dopamine. We herein describe a novel series of functionalized triazolo[4,5-d]pyrimidine derivatives that display functional antagonism of the A(2A) receptor. Optimization of these compounds has resulted in improvements in potency, selectivity, and the pharmacokinetic properties of key derivatives. These efforts have led to the discovery of 60 (V2006/BIIB014), which demonstrates strong oral activity in commonly used models of Parkinson's disease. Furthermore, this derivative has shown excellent preclinical pharmacokinetics and has successfully completed phase I clinical studies. This compound is presently undergoing further clinical evaluation in collaboration with Biogen Idec.

Published
2009
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