126874-83-7Relevant academic research and scientific papers
Synthesis and Dopamine Receptor Affinities of Enantiomers of 2-Substituted Apomorphines and their N-n-Propyl Analogues
Gao, Yigong,Baldessarini, Ross J.,Kula, Nora S.,Neumeyer, John L.
, p. 1800 - 1805 (1990)
Syntheses of (R)-(-)-2-methoxyapomorphine (R-8), its antipode S-8, and its (R)-(-)-N-n-propyl R-9 derivative are described.The dopaminergic receptor affinities of these compounds and their 2-unsubstituted counterparts (R)-(-)-apomorphine (R(-)-APO, R-1), (S)-(+)-apomorphine (S(+)-APO, S-1), and (R)-(-)-N-n-propylnorapomorphine (R(-)-NPA, R-2), as well as those of (R)-(-)-2-chloroapomorphine (R(-)-2-Cl-APO, R-6), (R)-(-)-2-bromoapomorphine (R(-)-2-Br-APO, R-6), were determined with tissue membrane preparations of corpus striatum from rat brain.Contribution of both an N-n-propyl and a 2-hydroxy in (R)-(-)-2-hydroxy-N-n-propylnorapomorphine (R(-)-2-OH-NPA, R-7) or a methoxy group in (R)-(-)-2-methoxy-N-n-propylnorapomorphine (R(-)-2-OCH3-NPA, R-9) produced the highest D2 affinity (0.053 and 0.17 nM) and D2 over D1 selectivity (17300 and 10500 times) of the compounds evaluated.The structure-affinity relationships of these 2-substituted aporphines suggest that secondary binding sites of D2 receptors interact with 2-substituents on the A ring of aporphines through H-bonding.
A two-step one-pot radiosynthesis of the potent dopamine D 2/D3 agonist PET radioligand [11C]MNPA
Steiger,Finnema,Raus,Schou,Nakao,Suzuki,Pike,Wikstroem,Halldin
, p. 158 - 165 (2009)
(R)-(-)-2-[11C]Methoxy-N-n-propylnorapomorphine ([ 11C]MNPA ([11C]2)) is an agonist radioligand of interest for imaging D2/ D3 receptors in vivo. Here we sought to develop an improved radiosynthesis of this radioligand. Reference 2 was synthesized in nine steps with an overall yield of about 5%, starting from codeine. Trimethylsilyldiazomethane proved to be a practical improvement in comparison to diazomethane in the penultimate methylation step. A protected precursor for radiolabeling ((R)-(-)-2-hydroxy-10,11-acetonide-N-n- propylnoraporphine, 4) was prepared from (R)-(-)-2-hydroxy-N-n- propylnorapomorphine (1) in 30% yield. [11C]2 was prepared from 4 via a two-step one-pot radiosynthesis. The first step, methylation of 4 with [ 11C]methyl triflate, occurred in quantitative radiochemical yield. The second step, deprotection of the catechol moiety with HCl and heat, yielded 60-90% of [11C]2 giving an overall incorporation yield from [ 11C]methyl triflate of 60-90%. In a typical run more than 1 GBq of [11C]2, was produced from carbon-11 generated from a 10-min proton irradiation (16 MeV; 35 μA) of nitrogen-hydrogen target gas. The radiochemical purity of [11C]2 was > 99% and specific radioactivity at the time of injection was 901±342 GBq/μmol (n = 10). The total synthesis time was 35-38 min from the end of radionuclide production. The identity of [11C]2 was confirmed by comparing its LC-MS/MS spectrum with those of reference 2 and (R)-(-)-10-methoxy-2,11-dihydroxy-N-n- propylnoraporphine. Copyright
First synthesis and utilization of oripavidine - A concise and efficient route to important morphinans and apomorphines
Sipos, Attila,Berenyi, Sandor,Antus, Sandor
, p. 1359 - 1365 (2009)
The synthesis and transformation of oripavidine (8) offer an efficient and simple route to highly active dopamine agonist apomorphines and a variety of important 14β-hydroxy-morphinan derivatives. Natural origin thebaine (6), the starting compound of the
