Improved synthesis and antitumor evaluation of 5,8-dideazaisofolic acid and closely related analogs
| Autor: | J. E. Mcgill, S. J. Harmon, Y. C. S. Yang, J. B. Hynes, W. L. Washtien |
|---|---|
| Rok vydání: | 1984 |
| Předmět: |
Chemical Phenomena
Stereochemistry Antineoplastic Agents Adenocarcinoma Cell Line Indirect evidence Structure-Activity Relationship Drug Discovery medicine Humans Gastrointestinal Neoplasms Antitumor activity chemistry.chemical_classification Bicyclic molecule Chemistry Stereoisomerism Biological activity Normal folate In vitro Methotrexate Dicarboxylic acid Mechanism of action Quinazolines Folic Acid Antagonists Molecular Medicine medicine.symptom |
| Zdroj: | Journal of Medicinal Chemistry. 27:232-235 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00368a023 |
| Popis: | A new synthetic route to 5,8-dideazaisofolic acid (IAHQ) is described which precludes the possibility of contamination due to its 4-amino counterpart 5,8-dideazaisoaminopterin. Substitution of D-glutamic acid in this synthetic scheme gave D-IAHQ. The 9-formyl, 9-methyl, 5-methyl, and 5,9-dimethyl modifications of IAHQ were also prepared. These compounds, together with several structurally related or isomeric analogues, were studied for inhibitory effects upon the growth of four human gastrointestinal adenocarcinoma cell lines in vitro. In general, the compounds having a normal folate configuration at positions 9 and 10 are more active than their reversed bridge isomers. The lack of antitumor activity of D-IAHQ provides indirect evidence concerning the mechanism of action of IAHQ. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|