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BioAssay: AID 177776

Analgesic activity measured by rat tail flick assay following s.c. administration.

Conjugate addition of lithium dialkyl cuprates to codeinone (3) gave as the major product a series of 8 beta-alkyldihydrocodeinones 4a-m. A low yield of the 8 alpha-isomer 6 was isolated in several cases. 8 beta-Acyldihydrocodeinones 10 were prepared by the addition of acyl carbanion equivalents (protected cyanohydrin method or lithium bis(alpha-ethoxyvinyl)cuprate) to 3 followed by hydrolysis. 8 more ..
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 Tested Compounds
 Tested Compounds
All(15)
 
 
Active(7)
 
 
Unspecified(8)
 
 
 Tested Substances
 Tested Substances
All(16)
 
 
Active(8)
 
 
Unspecified(8)
 
 
 Related BioAssays
 Related BioAssays
AID: 177776
Data Source: ChEMBL (175045)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-20
Modify Date: 2014-05-19

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 7
Description:
Title: Analgesic narcotic antagonists. 1. 8 beta-Alkyl-, 8 beta-acyl-, and 8 beta-(tertiary alcohol)dihydrocodeinones and -dihydromorphinones.

Abstract: Conjugate addition of lithium dialkyl cuprates to codeinone (3) gave as the major product a series of 8 beta-alkyldihydrocodeinones 4a-m. A low yield of the 8 alpha-isomer 6 was isolated in several cases. 8 beta-Acyldihydrocodeinones 10 were prepared by the addition of acyl carbanion equivalents (protected cyanohydrin method or lithium bis(alpha-ethoxyvinyl)cuprate) to 3 followed by hydrolysis. 8 beta-Acetyldihydrocodeine (12) was reacted with MeLi or n-BuLi to give tertiary alcohols 13, which were oxidized to target dihydrocodeinones 14. The 8 beta-substituted compounds with unsaturated (4c,f,m), branched (4d,g,i-k), or large straight-chain (4h,l) alkyl groups, as well as the acyl (10a-d) and tertiary alcohol (14a,b) derivatives, were less active than dihydrocodeinone (4n) in the mouse writhing and rat tail-flick analgesic assays. The analgesically active 8 beta-methyl (4a) and 8 beta-ethyl (4b) compounds were converted to N-(cyclopropylmethyl)- and N-(cyclobutylmethyl)dihydronorcodeinones (17 and 18) and -dihydronormorphinones (19 and 20). Some of these compounds had mixed agonist-antagonist profiles of action. One of these compounds, N-(cyclopropylmethyl)-8 beta-ethyldihydronorcodeinone (17b), has been selected for further study in man.
(PMID: 6153723)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Putative Target:
ChEMBL Target ID: 50597
Target Type: ORGANISM
Pref Name: Rattus norvegicus
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Functional
Assay Data Source: Scientific Literature
BAO: Assay Format: organism-based format
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1ED50*ED50 PubChem standard valueFloatμM
2ED50 activity commentED50 activity commentString
3ED50 standard flagED50 standard flagInteger
4ED50 qualifierED50 qualifierString
5ED50 published valueED50 published valueFloatμM
6ED50 standard valueED50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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