(R)‐ and (S)‐5‐hydroxy‐2‐(dipropylamino)tetralin (5‐OH DPAT): Assessment of optical purities and dopaminergic activities

Abstract

Racemic 5-hydroxy-2-(dipropylamino)tetralin (5-OH DPAT), a potent and selective dopamine (DA) D2-receptor agonist, was resolved into the enantiomers by a new method. The enantiomers of 5-OH DPAT were determined by chiral ion-pair chromatography using N-benzyloxycarbonylglycyl-L-proline as the counter ion. The enantiomeric purity of (R)-5-OH DPAT was found to be greater than 99.7%. The ability of the enantiomers to change the rat brain DOPA levels was evaluated in vivo. The results indicate that (R)-5-OH DPAT is a weakly potent DA D2-receptor antagonist.

Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade

“…The observed neuroprotective effects were proposed to stem from the synergistic effects of the molecule’s functionalities (e.g., dopamine agonist activity, Fe­(II/III) chelation, and antioxidant capacity). Yedlapudi et al presented two multifunctional DAs, DA-3 and DA-4 (called D-519 and D-520 , respectively by the authors; Figure ), which were constructed based on the structures of pramipexole and 5-OH-DPAT (another dopamine receptor agonist), respectively (Figure ). Both of these molecules could bind to dopamine receptors (i.e., D 2 L and D 3 isoforms) expressed in HEK-293 cells ( K i = 233 and 1.4 nM against D 2 L and D 3 receptors for DA-3 , respectively; K i = 42 and 0.35 nM against D 2 L and D 3 receptors for DA-4 , respectively), modify α-Syn aggregation, and exhibit neuroprotective properties against α-Syn-induced toxicity in PC12 cells and in a Drosophila model of synucleinopathy …”

Enantiomeric resolution of melatonin ligands receptors by liquid chromatography on amylose chiral stationary phases

“…It can be seen that decrease in the concentration polar modifier (ethanol: eluents A, B, G or 1-propanol: eluents C, D or 2-propanol: eluents E, F) in the mobile phase increases (k, Rs) parameters in a general manner both for 1 and 2 on Chiralpak AS [15,18]. This effect is illustrated in Figure 2 in the separation of compound la whose parameters (k, ct, Rs) are (1 95 [22,25].…”

“…Compounds I and 2 have a chiral center and as stereoisomers often show different pharmacological activities, and as a complement to biological study it is a prerequisite to separate the enantiomers of the compounds under investigation in order to obtain reliable pharmacological data. Chiral ion-pair chromatography, using N-benzoyloxycarbonylglycyl-L-proline as counter ion on a carbon column leads to the separation of aminotetralins [15]. In order to obtain a more rapid method, direct resolution, without any prederivatization, of the enantiomeric components was studied.…”

Synthesis of Pharmaceutically Relevant 2‐Aminotetralin and 3‐Aminochroman Derivatives via Enzymatic Reductive Amination

“…[2][3][4][5] Representative examples of these compounds are the former drug candidates Ebalzotan, [6] Alnespirone [7] and Robalzotan, [8] studied as potential antidepressant and anxiolytic treatments due to their antagonistic and agonistic effects at the 5-HT 1A receptor. Particular interest has been shown in 5-OH-DPAT [9] and Rotigotine [10] as therapeutic ingredients for Parkinsons disease, with the latter (commercially known as Neupro ) reaching a market value of E 311 million in 2020 (Figure 1). [11] Conventional approaches towards the synthesis of 2-aminotetralin and 3-aminochroman derivatives have been led by classical diastereomeric resolution of racemic amines with chiral resolving agents.…”