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BioAssay: AID 127831

Narcotic agonist activity using acetic acid induced writhing in the mouse upon subcutaneous administration

Structure-activity correlations in 7 beta-(arylalkyl)-3-methoxy- or hydroxy-4,5 alpha-epoxymorphinans have been investigated. 6 beta-Hydroxy-7 alpha-hydroxymethyl compounds 7 with 7 beta-substituents CH2CH2R [a, R = H; b, R = CH2CH3; c, R = C6H5; d, R = CH2C6H5; f, R = CH2CH2C6H5; g, R = (CH2)3C6H5; h, R = (CH2)4C6H5] were prepared. Wittig condensations with previously reported 4,5 alpha-epoxy-7 more ..
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 Tested Compounds
 Tested Compounds
All(68)
 
 
Unspecified(68)
 
 
 Tested Substances
 Tested Substances
All(68)
 
 
Unspecified(68)
 
 
AID: 127831
Data Source: ChEMBL (125063)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-20

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: Analgesic narcotic antagonists. 15. Potent narcotic agonist 7 beta-(arylalkyl)-4,5 alpha-epoxymorphinans.

Abstract: Structure-activity correlations in 7 beta-(arylalkyl)-3-methoxy- or hydroxy-4,5 alpha-epoxymorphinans have been investigated. 6 beta-Hydroxy-7 alpha-hydroxymethyl compounds 7 with 7 beta-substituents CH2CH2R [a, R = H; b, R = CH2CH3; c, R = C6H5; d, R = CH2C6H5; f, R = CH2CH2C6H5; g, R = (CH2)3C6H5; h, R = (CH2)4C6H5] were prepared. Wittig condensations with previously reported 4,5 alpha-epoxy-7 beta-formyl-7 alpha-(hydroxymethyl)-6 beta, 7 alpha-O-isopropylidene-3-methoxy-17-methylmorphinan-6 beta-ol (3), followed by dilute acid removal of the blocking group and then hydrogenation, gave saturated compounds 7. Compounds with a 6 alpha, 7 alpha-oxymethylene ring. 18c,d,f,g, were prepared from 7 beta-formyl derivative 16 and the appropriate Wittig reagent, followed by hydrogenation. Both the 6 beta-hydroxy-7 alpha-hydroxymethyl and 6 alpha, 7 alpha-oxymethylene series containing 7 beta-arylalkyl groups with an alkyl chain length of 2 to 4 ar potent narcotic agonists. The most potent 17-methyl compound, 4,5 alpha-epoxy-7 alpha-(hydroxymethyl)-17-methyl-17 beta-(4-phenylbutyl)morphinan-3,6 beta-diol (8f) was 700 times more potent than morphine in the acetic acid induced mouse writhing assay. 17-Methyl compounds in the c, d, f, g series were converted to 17-cyclopropylmethyl (P series) or 17-cyclobutylmethyl (B series) derivatives. Narcotic antagonistic activity could not be demonstrated for these potent agonist 17-cycloalkylmethyl derivatives. These pharmacological results parallel those previously reported for tertiary alcohol derivatives of the endo-ethenotetrahydrooripavines. Structureal considerations confirm the existence of a lipophilic site extending upward and outward from where the C ring of morphine and congeners bind to opiate receptors.
(PMID: 6864732)
Comment
Putative Target:

ChEMBL Target ID: 50594
Target Type: ORGANISM
Pref Name: Mus musculus
Organism: Mus musculus
Tax ID: 10090
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: organism-based format

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1ED50 activity commentED50 activity commentString
2ED50 standard flagED50 standard flagInteger
3ED50 qualifierED50 qualifierString
4ED50 published valueED50 published valueFloatuM kg-1
5ED50 standard valueED50 standard valueFloatumol.kg-1

Data Table (Concise)
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