| Abstract: |
Synthesis of trans-and cis-tetrahydrodipyrazino[1, 2-a:1', 2'-d]pyrazine-1, 3, 7, 9(2H, 4H, 8H, 10H)-tetrone analogues 10 and 11 belonging to the bis(dioxopiperazine) class of antitumor agents and their bis(morpholinomethyl) derivatives 12 and 13 are described with use of 2, 5-dimethylpyrazine as the starting material. Synthetic studies utilizing 3, 6-disubstituted 2, 5-dioxopiperazine precursors are included. Evaluation of 10–13 in the Lewis Lung carcinoma model indicated the bis(morpholinomethyl) analogue cis-13 to be antimetastatic, whereas the trans isomer 12 was toxic at a similar dose effecting a decrease in the life span of treated mice. The parent bis(dioxopiperazines) 10 and 11 were ineffective as antitumor or antimetastatic drugs. © 1985, American Chemical Society. All rights reserved. |
| Keywords: |
cancer chemotherapy; nonhuman; comparative study; antineoplastic agent; mouse; animal; mice; pyrazines; animal experiment; animal model; drug structure; drug synthesis; histology; chemistry; morpholines; neoplasms, experimental; magnetic resonance spectroscopy; drug toxicity; neoplasm transplantation; therapy; nuclear magnetic resonance; synthesis; lewis carcinoma; stereoisomerism; etiology; drug identification; intoxication; respiratory system; drug comparison; new drug; female; priority journal; support, u.s. gov't, p.h.s.; drug analysis; tetrahydro 2,8 bis(morpholinomethyl)dipyrazino[1,2 a:1',2' d]pyrazine 1,3,7,9(2h,4h,8h,10h) tetrone; tetrahydrodipyrazino[1,2 a:1',2' d]pyrazine 1,3,7,9(2h,4h,8h,10h) tetrone
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