| Abstract | Antagonism of the adenosine A2A receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A2A antagonist SCH 58261 as a starting point, we identified the potent and selective (vs. A1) antagonist 11h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity. |
| Authors | Bernard R Neustadt, Jinsong Hao, Neil Lindo, William J Greenlee, Andrew W Stamford, Deen Tulshian, Ennio Ongini, John Hunter, Angela Monopoli, Rosalia Bertorelli, Carolyn Foster, Leyla Arik, Jean Lachowicz, Kwokei Ng, Kung-I Feng
(Affiliation: Department of Chemical Research, , Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. bernard.neustadt at spcorp.com)
|
| Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 17
Issue 5
Pg. 1376-80
(Mar 1 2007)
ISSN: 0960-894X England |
| PMID | 17236762
(Publication Type: Journal Article)
|
| Chemical References |
- Piperazines
- Pyrimidines
- Receptor, Adenosine A2A
- piperazine
|
| Topics |
- Administration, Oral
- Animals
- Catalepsy
(chemically induced, drug therapy)
- Disease Models, Animal
- Parkinson Disease
(drug therapy)
- Piperazines
(administration & dosage, chemical synthesis, pharmacokinetics)
- Pyrimidines
(administration & dosage, chemical synthesis, pharmacokinetics)
- Rats
- Receptor, Adenosine A2A
(antagonists & inhibitors)
- Structure-Activity Relationship
- Substrate Specificity
- Treatment Outcome
|
