Synthesis and antitumor activity of 5-deaza-5,6,7,8-tetrahydrofolic acid and its N10-substituted analogues.
Syntheses of 5-deaza-5,6,7,8-tetrahydrofolic acid (7a) and its 10-formyl (7b), 10-acetyl (7c), and 10-methyl (7d) derivatives are described. These compounds, prepared as analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), the lead compound of a new class of folate antimetabolites, exhibit potent growth inhibition against leukemic cells in culture as well as substantial antitumor activity against transplantable murine solid tumors in vivo.
Taylor
E C
EC
Department of Chemistry, Princeton University, New Jersey 08544.
Hamby
J M
JM
Shih
C
C
Grindey
G B
GB
Rinzel
S M
SM
Beardsley
G P
GP
Moran
R G
RG
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D009584:Nitrogen; D011687:Purines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013763:Tetrahydrofolates / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011687:Purines; D013763:Tetrahydrofolates; C060147:5-deaza-5,6,7,8-tetrahydrofolic acid; D009584:Nitrogen