Journal article
Introduction of a putative dopaminergic prodrug moiety into a 6,7-substitution pattern characteristic of certain 2-aminotetralin dopaminergic agonists
Journal of medicinal chemistry, Vol.32(9), pp.2210-2214
09/01/1989
DOI: 10.1021/jm00129a029
PMID: 2570153
Abstract
On the basis of the premise that the dopaminergic agonist profile of 2-(di-n-propylamino)-5-hydroxy-6-methyltetralin (1a) is due to in vivo oxidation of the 6-methyl moiety and that la may represent a novel prodrug strategy, the vicinal methyl-hydroxyl substitution pattern was incorporated into the 6- and 7-positions of 2-(di-n-propylamino)tetralin to give the 6-methyl-7-hydroxy and 6-hydroxy-7-methyl isomers 8 and 9, respectively. A multistep synthetic approach was devised which permitted preparation of target molecules 8 and 9. Pharmacological data revealed that both target compounds exhibit modest dopamine-like effects in the cardioaccelerator nerve assay in the cat, but neither appeared to be metabolically activated as was the case with 1a. The effects of 9 (but not of 8) were antagonized by pretreatment with haloperidol. Thus, the 5-hydroxy-6-methyl substitution pattern in the 2-aminotetralins remains unique as a dopaminergic agonist prodrug structure.
Details
- Title: Subtitle
- Introduction of a putative dopaminergic prodrug moiety into a 6,7-substitution pattern characteristic of certain 2-aminotetralin dopaminergic agonists
- Creators
- Joseph G CannonClaire Diane TrueJohn Paul LongRanbir K BhatnagarPaul LeonardJan R Flynn
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.32(9), pp.2210-2214
- Publisher
- American Chemical Society
- DOI
- 10.1021/jm00129a029
- PMID
- 2570153
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Language
- English
- Date published
- 09/01/1989
- Academic Unit
- Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006432302771
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