ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Opiate antagonists stimulate the release of LH and might, therefore, contribute to an innovative therapy for the treatment of numerous clinical syndromes characterized by hypofunction of the HHG axis. The purpose of this work was to design and synthesize pure opiate antagonists useful for this therapy. Me, Et, Pr, and PhCH2 groups were introduced at the crucial 14β-position of morphines and morphinans via a hetero-Diels-Alder key step starting from thebaine derivative 1 and tested for opiate antagonism and LH-stimulating activity. Me-, Et-, and Pr-substituted compounds 11a-c were stronger antagonists than naltrexone, whereas Pr and PhCH2 substituents in 11c, 11d, 9d, 9d3, 9d4, and 9d5 led to orally active LH stimulators. Based on our finding that the μ-antagonists 12 and 11b5 showed no LH stimulation, we conclude that a combination of both μ-and χ-antagonism is necessary for potent LH stimulation.
Additional Material:
2 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19900730212
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