Journal article
Preparation and opioid activity of analogs of the analgesic dipeptide 2,6-dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide
Journal of medicinal chemistry, Vol.35(2), pp.223-233
01/01/1992
DOI: 10.1021/jm00080a005
PMID: 1346276
Abstract
A number of analogues of the recently disclosed analgesic dipeptide 2,6-dimethyl-l-tyrosyl-d-alanine-phenylpropylamide (SC-39566,2) were prepared. These analogues contained oxymethylene, aminomethylene, ketomethylene, bismethylene, and trans double bond (including vinyl fluoride) isosteric replacements for the amide bond between the d-alanine and phenylpropylamine units in 2. These compounds were tested in opioid binding assays and in the mouse writhing assay for analgesic activity. Though not as potent as 2, the oxymethylene, and trans double bond isosteres showed analgesic activity. The aminomethylene analogues also showed binding activity in subnanomolar concentrations at the μ receptor. The amide bond between 2,6-dimethyl-l-tyrosine and d-alanine units seems to be critical for opioid activity.
Details
- Title: Subtitle
- Preparation and opioid activity of analogs of the analgesic dipeptide 2,6-dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide
- Creators
- Nizal S ChandrakumarPeter K YonanAwilda StapelfeldMichael SavageElaine RorbacherPatricia C ContrerasDonna Hammond
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.35(2), pp.223-233
- DOI
- 10.1021/jm00080a005
- PMID
- 1346276
- NLM abbreviation
- J Med Chem
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 01/01/1992
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006434302771
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