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ID: ALA4339205

Journal: Bioorg Med Chem Lett

Title: Design, synthesis, and biological evaluation of novel pyrrolo[1,2-a]pyrazine derivatives.

Authors: Kim J, Park M, Choi J, Singh DK, Kwon HJ, Kim SH, Kim I.

Abstract: A pyrrolo[1,2-a]pyrazine-based chemical territory was expanded via construction of new chemical library with distinctive substitution patterns, which was made possible by regiodivergent electrophilic acylation followed by aldol condensation. Biological screening of the compounds in this class revealed that the viability of human lymphoma U937 cells was strongly inhibited by 6b with a methoxy group at the o-position of the aromatic ring, but not by compounds 6t-w bearing a halogen at the o-position. Furthermore, 6x having a 2,4-dimethoxyphenyl group inhibited the survival of U937 cells more potently than 6b. In contrast, 6y possessing a 2,5-dimethoxyphenyl moiety did not show effective inhibition, implying the importance of orientation of the substituent(s) around the benzene ring. The anticancer action of 6x with safe therapeutic window could be associated with the FTase-p38 signaling axis.

CiteXplore: 30954427

DOI: 10.1016/j.bmcl.2019.03.044