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.
| Original language | English |
|---|---|
| Pages (from-to) | 1350-1356 |
| Number of pages | 7 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 29 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2019 Jun 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Cite this
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Design, synthesis, and biological evaluation of novel pyrrolo[1,2-a]pyrazine derivatives. / Kim, Jinwoo; Park, Mikyung; Choi, Jiwon; Singh, Dileep Kumar; Kwon, Ho Jeong; Kim, Seong Hwan; Kim, Ikyon.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 11, 01.06.2019, p. 1350-1356.Research output: Contribution to journal › Article
TY - JOUR
T1 - Design, synthesis, and biological evaluation of novel pyrrolo[1,2-a]pyrazine derivatives
AU - Kim, Jinwoo
AU - Park, Mikyung
AU - Choi, Jiwon
AU - Singh, Dileep Kumar
AU - Kwon, Ho Jeong
AU - Kim, Seong Hwan
AU - Kim, Ikyon
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85063739826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063739826&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2019.03.044
DO - 10.1016/j.bmcl.2019.03.044
M3 - Article
C2 - 30954427
AN - SCOPUS:85063739826
VL - 29
SP - 1350
EP - 1356
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 11
ER -