77761-73-0Relevant academic research and scientific papers
Aporphines. 34. (-)-2,10,11-Trihydroxy-N-n-propylnoraporphine, a novel dopaminergic aporphine alkaloid with anticonvulsant activity
Neumeyer,Law,Meldrum,Anlezark,Watling
, p. 898 - 899 (1981)
(-)-2,10,11-Trihydroxy-N-n-propylnoraporphine (TNPA, 2c) has been synthesized from thebaine (3a), via northebaine (3b), normophothebaine (2a), and alkylation to the N-propyl derivative 2b. O-Demethylation gave the desired product 2c. Compound 2c showed activity comparable to its 10,11-dihydroxy counterpart (NPA, 1b) on the stimulation of dopamine-sensitive adenylate cyclase in carp retinal homogenates. The evaluation of 2c on audiogenic seizures in mice, in the protection against paroxysimal EEG and myoclonic response to photic stimulation in the baboon, revealed a similar pharmacological profile in comparison to NPA and apomorphine, with TNPA showing a prolonged duration of action in abolishing myoclonic response to photic stimulation in the baboon.
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
experimental part, p. 158 - 165 (2010/06/20)
(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
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 (2007/10/02)
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.
Aporphines. 36. Dopamine Receptor Interactions of Trihydroxyaporphines. Synthesis, Radioreceptor Binding, and Striatal Adenylate Cyclase Stimulation of 2,10,11-Trihydroxyaporphines in Comparison with Other Hydroxylated Aporphines
Neumeyer, John L.,Arana, George W.,Law, Say-Jong,Lamont, Jeffrey S.,Kula, Nora S.,Baldessarini, Ross J.
, p. 1440 - 1445 (2007/10/02)
The presence of the A ring of aporphines and the addition of substituents to it and to other portions of the aporphine ring systems can extend explorations of the dimensions and other characteristics of the dopamine receptor.Accordingly, the synthesis and some physical and pharmacological properties of a series of (-)-2,10,11-trihydroxyaporphines (3a-g) are described.Structure-activity relationships among mono-, di-, and trihydroxyaporphines were evaluated against the high-affinity (nanomolar) binding of apomorphine (APO) and spiroperidol (SPR) with a subcellular fraction (P4) of caudate nucleus from bovine brain.In addition, DA-sensitive adenylate cyclase activity was evaluated in homogenates of rat brain striatal tissue.The rank order of displacement of APO by potent aporphines (IC5030 nM) correlated approximately with their ability to stimulate cyclic AMP synthesis.Potency orders against the two ligands were dissimilar; for example, increasing the size of N6-alkyl substituents increased potency vs. SPR but not vs. APO binding.Moreover, SPR binding correlated poorly with cyclase activity or APO binding, suggesting a closer relationship of APO binding to dopamine-sensitive adenylate cyclase activity.
