Synthesis of 4‐[(1,3‐diaminopyrrolo[3′,4′:4,5]pyrido[2,3‐d]‐pyrimidin‐8‐yl)benzoyl]‐L‐glutamic acid as a potential antifolate Journal Article
| Authors: | Su, T. L.; Yang, Y. K.; Huang, J. T.; Ren, W. Y.; Watanabe, K. A.; Chou, T. C. |
| Article Title: | Synthesis of 4‐[(1,3‐diaminopyrrolo[3′,4′:4,5]pyrido[2,3‐d]‐pyrimidin‐8‐yl)benzoyl]‐L‐glutamic acid as a potential antifolate |
| Abstract: | This paper is dedicated to the memory of Professor Roland K. Robins The synthesis of 4‐[(1,3‐diaminopyrrolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidin‐8‐yl)benzoyl]‐L‐glutamic acid (18), a potential antifolate and anticancer agent, has been achieved starting from 1,4‐dibromobutan‐2‐ol with alkyl p‐aminobenzoic acids. Condensation of these two agents gave 1‐(4‐alkoxycarbonylphenyl)pyrrolidin‐3‐ols 7a,b, which were oxidized to the corresponding pyrrolidin‐3‐one derivatives 8a,b. Compounds 8a,b were converted into 1,3‐diamino‐8‐(4‐alkoxycarbonylphenyl)‐7,8‐dihydro‐9H‐pyrrolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 12a,b in 4 steps. Saponification of 12b the benzoate ester and coupling with di‐tert‐butyl glutamate afforded a mixture of 7,8‐dihydro product 16 and its aromatized derivative 17. Finally hydrolysis of esters 16 or 17 gave only the title compound 18. The 7,8‐dihydro tricyclic derivatives were easily air‐oxidized to form their fully aromatized compounds. The title compound 18 was one tenth less active than MTX against HL‐60 cells in culture. Copyright © 1993 Journal of Heterocyclic Chemistry |
| Keywords: | controlled study; unclassified drug; human cell; methotrexate; cytotoxicity; drug synthesis; leukemia cell; folic acid antagonist; glutamic acid derivative; human; article; 4 [(1,3 diaminopyrrolo[3',4':4,5]pyrido[2,3 d]pyrimidin 8 yl)benzoyl]glutamic acid |
| Journal Title: | Journal of Heterocyclic Chemistry |
| Volume: | 30 |
| Issue: | 5 |
| ISSN: | 0022-152X |
| Publisher: | Wiley-Blackwell Publishing, Inc. |
| Date Published: | 1993-10-01 |
| Start Page: | 1437 |
| End Page: | 1443 |
| Language: | English |
| DOI: | 10.1002/jhet.5570300542 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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