Synthesis and antimetastatic properties of stereoisomeric tricyclic bis(dioxopiperazines) in the Lewis lung carcinoma model

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.

Interfacial supramolecular biomimetic epoxidation catalysed by cyclic dipeptides

“…Finally, with 33a-35a we verified the efficiency of CDPs with only chiral side chains on the cyclic core (Table 1, entries [31][32][33]. Interestingly, CDP with one isobutyl 33a provided racemic epoxychalcone.…”

Tuning the porosity of lanthanide MOFs with 2,5-pyrazinedicarboxylate and the first in situ hydrothermal carboxyl transfer

“…We have carefully checked the purity of the reactant 2,5-pyrazinedicarboxylic acid to assure that 2,6-pyrazinedicarboxylic acid was absent in the starting material by two approaches. Firstly, the melting points of the two isomers differ markedly by over 50 C (271-2 17 and 218 C 19 for 2,5-and 2,6-pyrazinedicarboxylic acids, respectively). The fact that the melting point of our prepared 2,5-pyrazinedicarboxylic acid was measured to be exactly the same as the literature value 17 proved this ligand was quite pure.…”

Amelioration of Anthracycline-Induced Cardiotoxicity by Organic Chemicals

“…but not ds-2, were active in this assay (180). To further define their geometrical requirements, the tetraazaperhydrophenanthrene diastereomers were synthesized (181). In these compounds there cannot be a cisoid relationship of dioxopiperazine rings.…”

“…In this case (Scheme VI), formal bond disconnection of one carbonyl group from the central piperazine ring of the perhydrophenanthrenes and rebonding on the opposite carbon of the central ring provide the diastereomeric cisand rra^-tetraazaperhydroanthracene-type bis(dioxopiperazine)s (181). …”

“…In the post amputation schedule (Table VI) only the bis(morpholinomethyl) derivative of l,4-d5-tetraazaperhydroanthracene is active (181). The bis(morpholinomethyl) derivatives of bis(dioxopiperazine)s are of interest because in some cases (but not all) morpholinomethyl substitution increases water solubility and in many instances also increases antitumor activity (7,2) (Scheme VII).…”