- Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination
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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.
- Citoler, Joan,Harawa, Vanessa,Marshall, James R.,Bevinakatti, Han,Finnigan, James D.,Charnock, Simon J.,Turner, Nicholas J.
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supporting information
p. 24456 - 24460
(2021/10/19)
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- NEW AMINOTETRALINE DERIVATIVES
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The present application relates to compounds of formula (I): and pharmaceutically acceptable salts and solvates thereof, wherein the substituents are as defined herein, compositions containing such compounds and the uses of such compounds in producing med
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Page/Page column 33
(2011/07/09)
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- New aminotetraline derivatives
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The present application relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein the substituents are as defined herein, compositions containing such compounds and the uses of such compounds in producing medi
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Page/Page column 18-19
(2011/07/09)
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- 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
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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.
- Sonesson,Barf,Nilsson,Dijkstra,Carlsson,Svensson,Smith,Martin,Duncan,King,Wikstrom
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p. 1319 - 1329
(2007/10/02)
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- METHOD OF INHIBITING GASTRIC ACID SECRETION
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The present invention provides a method of inhibiting gastric acid secretion in mammals by administering a 5-HT1A agonist compound or a pharmaceutically acceptable salt thereof.
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- METHOD OF INHIBITING GASTRIC ACID SECRETION WITH BENZODIOXANES
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The present invention provides a method of inhibiting gastric acid secretion in mammals by administering a 5-HT1A agonist compound or a pharmaceutically acceptable salt thereof.
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- 2-(Alkylamino)tetralin Derivatives: Interaction with 5-HT1A Serotonin Binding Sites
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8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a selective 5-HT1A serotonin agonist.Derivatives of 8-OH-DPAT with amine substituents larger or more bulky than n-propyl appear to be inactive in a presynaptic biochemical assay measuring ag
- Naiman, Noreen,Lyon, Robert A.,Bullock, Amy E.,Rydelek, Laura T.,Titeler, Milt,Glennon, Richard A.
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p. 253 - 256
(2007/10/02)
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