Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin Journal Article
| Authors: | DeGraw, J. I.; Colwell, W. T.; Piper, J. R.; Sirotnak, F. M. |
| Article Title: | Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin |
| Abstract: | Successive alkylation of dimethyl homoterephthalate with propargyl bromide and 2,4-diamino-6-(bromomethyl)pteridine followed by ester saponification at room temperature afforded 2,4-diamino-4-deoxy-10-carboxy-10-propargyl-10-deazapteroic acid. The 10-COOH was readily decarboxylated by heating in DMSO at a temperature of only 120 °C to yield the diamino-10-propargyl-10-deazapteroic acid intermediate. Coupling with diethyl l-glutamate and ester hydrolysis gave the title compound. The 10-propargyl analogue was about 5 times more potent than MTX as an inhibitor of growth in L1210 cells, but was only one-third as potent as an inhibitor of DHFR from L1210. The analogue was transported inward very effectively in L1210 cells showing a 10-fold advantage over MTX. At a dose of 36 mg/kg the 10-propargyl compound caused shrinkage of the E0771 solid murine mammary tumor to only 1% of untreated controls. © 1993, American Chemical Society. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; antineoplastic agents; note; methotrexate; animal cell; mouse; animal; mice; animal tissue; animal model; antineoplastic activity; drug potency; drug structure; drug synthesis; structure-activity relationship; breast tumor; aminopterin; mammary neoplasms, experimental; 10 deazaaminopterin; temperature dependence; 10 propargyl 10 deazaaminopterin; leukemia l1210; female; priority journal; support, u.s. gov't, p.h.s. |
| Journal Title: | Journal of Medicinal Chemistry |
| Volume: | 36 |
| Issue: | 15 |
| ISSN: | 0022-2623 |
| Publisher: | American Chemical Society |
| Date Published: | 1993-07-01 |
| Start Page: | 2228 |
| End Page: | 2231 |
| Language: | English |
| DOI: | 10.1021/jm00067a020 |
| PUBMED: | 8340923 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
