404848-24-4Relevant academic research and scientific papers
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists
Shah, Unmesh,Lankin, Claire M.,Boyle, Craig D.,Chackalamannil, Samuel,Greenlee, William J.,Neustadt, Bernard R.,Cohen-Williams, Mary E.,Higgins, Guy A.,Ng, Kwokei,Varty, Geoffrey B.,Zhang, Hongtao,Lachowicz, Jean E.
scheme or table, p. 4204 - 4209 (2009/04/10)
SCH 58261 is a reported adenosine A2A receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A1 receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A2A receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A2A receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 μM at physiological pH.
2-Substituted-1,2,3,4-tetrahydroisoquinolines and chiral 3-carboxyl analogues from N-benzotriazolylmethyl-N-phenethylamines
Katritzky, Alan R,He, Hai-Ying,Jiang, Rong,Long, Qiuhe
, p. 2427 - 2434 (2007/10/03)
N-Benzotriazolylmethyl-N-phenethylamines 5a-5c and 11a-11c cyclize in the presence of aluminum chloride to produce 1,2,3,4-tetrahydroisoquinolines 6a-6c and 12a-12c (70-89%) via electrophilic attack of a transient iminium cation X on the tethered phenyl r
