500733-22-2Relevant academic research and scientific papers
Enantiospecific synthesis and receptor binding of novel dopamine receptor ligands employing natural 4-hydroxyproline as a practical and flexible building block
Heindl, Cornelia,Huebner, Harald,Gmeiner, Peter
, p. 3153 - 3172 (2003)
Starting from natural 4-hydroxyproline, an ex-chiral pool approach is described giving access to 2-aminoalkylpyrrolidine derivatives that were used as chiral building blocks for the synthesis of bioactive 2-methoxybenzamide derivatives. The 4-hydroxy substituent can be displaced employing organocuprates as useful carbanion equivalents. Dopamine and serotonin binding studies involving the subtypes D1, D2long, D2short, D3 and D4 as well as 5-HT1A and 5-HT2, respectively, provided interesting insights into stereoselective structure activity relationships. The (2S,4R)-2-aminomethylpyrrolidine derivative ent-66 and the (2R,4S)-2- aminoethylpyrrolidine derivative 68 showed remarkable affinity and preference for the dopamine D3 and D4 receptor subtypes, respectively, both being putatively associated to the symptoms of schizophrenia.
