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A series of A-ring pyrrole compounds of duocarmycin bearing 4′-methoxy- beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the 4′-methoxy-beta- heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4′-methoxy-cinnamates. Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4′-methoxy-beta-heteroarylacrylates, compound 15b having a (4- methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4′-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4′-methoxy-beta-heteroarylacrylates had high aqueous solubility.

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Reference:
Pyridazine – Wikipedia,
Pyridazine | C4H4N3026 – PubChem