Inhibition of papilloma formation by analogues of 7,8-dihydroretinoic acid
| Autor: | Brahma P. Sani, Jerry L. Frye, James M. Riordan, Linda Simpson-Herren, Y. Fulmer Shealy, Donald L. Hill |
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| Rok vydání: | 2003 |
| Předmět: |
chemistry.chemical_classification
Skin Neoplasms Papilloma medicine.drug_class Stereochemistry Receptors Retinoic Acid Carboxylic acid Retinoic Acid Receptor alpha Ether Chemical synthesis Aldehyde In vitro chemistry.chemical_compound Mice chemistry Drug Discovery medicine Fatty Acids Unsaturated Molecular Medicine Animals Anticarcinogenic Agents Retinoid Aliphatic compound Cyanohydrin Protein Binding |
| Zdroj: | Journal of medicinal chemistry. 46(10) |
| ISSN: | 0022-2623 |
| Popis: | The design of analogues of 7,8-dihydroretinoic acid (7,8-dihydro-RA) was based on reported biological activities of this retinoid and its dihydro-TMMP(1) analogue and on structural hypotheses. 7-Oxa-7,8-dihydroretinoids (5, 6) were prepared by O-alkylation of phenoxides by methyl 8-bromo-3,7-dimethyl-2,4,6-octatrienoate. In some cases, C-alkylation also occurred. 7-Aza-8-oxo-7,8-dihydroretinoids (12, 13) were synthesized from benzeneamines and the acyl cyano or bromo derivative of the monomethyl ester of 3,7-dimethyl-2,4,6-octatriene-1,8-dioic acid. These monomethyl ester precursors were synthesized from the known analogous aldehyde via an O-trimethylsilyl cyanohydrin. 7-(2,3,5-Trimethylphenoxy)-3,5-dimethyl-2,4,6-octatrienoic acid (6b) was the most active of the 7-oxa-7,8-dihydro-RAs in inhibiting DMBA-initiated and TPA-promoted mouse-skin papillomas. The ED(50) was about 4-fold that of etretinate. Two additional 7-oxa-7,8-dihydro-RAs exhibited modest activity in the papilloma assay. Some of the 7-oxa-7,8-dihydro-RAs bind to CRABP and RARalpha. |
| Databáze: | OpenAIRE |
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