101403-25-2Relevant articles and documents
Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination
Citoler, Joan,Harawa, Vanessa,Marshall, James R.,Bevinakatti, Han,Finnigan, James D.,Charnock, Simon J.,Turner, Nicholas J.
supporting information, p. 24456 - 24460 (2021/10/19)
2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.
Synthesis and pharmacology of the enantiomers of the potential atypical antipsychotic agents 5-OMe-BPAT and 5-OMe-(2,6-di-OMe)-BPAT
Homan, Evert J.,Copinga, Swier,Unelius, Lena,Jackson, David M.,Wikstroem, Hkan V.,Grol, Cor J.
, p. 1263 - 1271 (2007/10/03)
The optically pure enantiomers of the potential atypical antipsychotic agents 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 5) and 5-methoxy-2-{N-[2-(2,6-dimethoxy)benzamidoethyl]-N-n-propylamino}tetralin [5-OMe-(2,6-di-OMe)-BPAT
Derivatives of (R)-2-amino-5-methoxytetralin: Antagonists and Inverse Agonists at the Dopamine D2A Receptor
Hoeoek, Berit Backlund,Brege, Cecilia,Linnanen, Tero,Mikaels, Aesa,Malmberg, Aesa,Johansson, Anette M.
, p. 2167 - 2172 (2007/10/03)
A series of N-arylmethyl substituted (R)-5-methoxy-2-(propylamino)tetralins has been prepared and evaluated for affinity and efficacy at dopamine (DA) D2A receptors. The novel compounds appeared to be antagonists or inverse agonists. (R)-2-(Be
Synthesis and evaluation of pharmacological and pharmacokinetic properties of monopropyl analogs of 5-, 7-, and 8-[[(trifluoromethyl)sulfonyl]oxy]-2- aminotetralins: Central dopamine and serotonin receptor activity
Sonesson,Barf,Nilsson,Dijkstra,Carlsson,Svensson,Smith,Martin,Duncan,King,Wikstrom
, p. 1319 - 1329 (2007/10/02)
In order to explore further the structure-activity relationships of serotonergic and dopaminergic ligands, a series of enantiopure 5-, 7-, or 8- triflate (-OTf)-substituted 2-(monopropylamino)-tetralins have been synthesized and evaluated in in vitro binding and in vivo biochemical and behavioral assays in rats. Consequently, the 8-OTf-substituted compound R- (+)-6 was found to be a potent and selective 5-HT(1A) (5-hydroxytryptamine) receptor agonist inducing a full-blown 5-HT syndrome in normal rats, while the corresponding 5-OTf-substituted compound S-(-)-12 was found to be a preferential dopamine (DA) autoreceptor agonist. A partial 5-HT syndrome was also observed for S-(-)-12, while the corresponding R-(+)-12 was found to be inactive at the DA and 5-HT receptors both in vitro and in vivo. Compounds 6 and 12 were found to be major urinary metabolites following oral administration of their dipropyl analogs (2 and 13, respectively). Thus 6 was proposed to be the metabolite responsible for the full-blown 5-HT syndrome seen after oral (but not subcutaneous) administration of 2. Similarly, 12 was proposed to be the metabolite responsible for the partial 5-HT syndrome seen after oral (but not subcutaneous) administration of 13. The bioavailability of R-(+)-6 (7.6 ± 1.1%) appeared to be slightly lower than that of 2 (11.2 ± 5.2%), although the in vitro metabolism of R-(+)-6 appeared to be slower than that of 2. Therefore first-pass metabolism was not thought to be the reason for the lower bioavailability of R-(+)-6, as compared to 2.
Fluorescent Probes for Dopamine Receptors: Synthesis and Characterization of Fluorescein and 7-Nitrobenz-2-oxa-1,3-diazol-4-yl Conjugates of D-1 and D-2 Receptor Ligands
Bakthavachalam, Venkatesalu,Baindur, Nandkishore,Madras, Bertha K.,Neumeyer, John L.
, p. 3235 - 3241 (2007/10/02)
Fluorescent probes have been designed and developed for dopamine D-1 and D-2 receptors.Fluorescein and/or NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist), SKF 38393 (D-1 agonist), and SKF 83566 (D-1 antagonist) were synthesized via their amino-functionalized analogues and all ligands were pharmacologically evaluated by measuring their ability to displace SCH 23390 and 3H)spiperone from D-1 and D-2 receptor sites in caudate putamen of monkeys (Macaca fascicularis).The fluorescein derivatives of PPHT andSKF 83566 and the NBD derivatives of spiperone and SKF 83566 retained the high affinity and selectivity of parent ligands.The NBD derivatives of PPHT showed higher D-2 receptor affinity and selectivity than their parent ligands.The enantiomers of the fluorescent derivatives of PPHT were also synthesized and were found to exhibit stereoselectivity in binding to the D-2 receptor, with the S enantiomers having a considerably higher affinity than their R analogues.In contrast to these results, the fluorescein derivative of SKF 38393 showed only a low affinity for the D-1 receptor.These fluorescein- and NBD-coupled D-1 and D-2 receptor ligands have considerable significance as potential probes in the study of distribution of the receptors at the cellular/subcellular level and of their mobility in membranes in normal/diseased states by use of fluorescence microscopic and fluorescence photobleaching recovery techniques, respectively.The development of these novel fluorescent probes should also provide new leads for the design and synthesis of additional fluorescent ligands with better fluorescent properties and/or higher affinity/selectivity for the DA receptors.
Structure-Activity Relationships of Dopaminergic 5-Hydroxy-2-aminotetralin Derivatives with Functionalized N-Alkyl Substituents
Seiler, Max P.,Stoll, Andre P.,Closse, Annemarie,Frick, Willy,Jaton, Annelise,Vigouret, Jean-Marie
, p. 912 - 917 (2007/10/02)
5-Hydroxy-2-aminotetralin derivatives in which one N-alkyl substituent carries a functional group have been prepared and their dopaminergic activities compared with those of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) and known ergolines.Several members of the series demonstrated high affinities in dopamine (DA) receptor binding and DA agonist properties in the rotational behavior model in the range of known potent ergolines.The results suggests that the accessory binding site for the larger N-alkyl substituent of the 5-hydroxy-2-aminotetralins can accommodate various neutral and bulky functionalities and is probably identical with the site(s) to which the 8-substituents of the ergolines bind.
Resolved Monophenolic 2-Aminotetralins and 1,2,3,4,4a,5,6,10b-Octahydrobenzoquinolines: Structural and Stereochemical Cosiderations for Centrally Acting Pre- and Postsynaptic Dopamine-Receptor Agonists
Wikstroem, Hakan,Andersson, Bengt,Sanchez, Domingo,Lindberg, Per,Arvidsson, Lars-Erik,et al.
, p. 215 - 225 (2007/10/02)
A detailed structure-activity relationship is revealed for resolved, centrally acting dopamine (DA) agonists acting on both pre- and postsynaptic DA receptors.The compounds resolved are 5- and 7-hydroxy-2-(di-n-propylamino)tetralin and cis- and trans-7-hy
