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

Jinwoo Kim, Mikyung Park, Jiwon Choi, Dileep Kumar Singh, Ho Jeong Kwon, Seong Hwan Kim, Ikyon Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)1350-1356
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number11
DOIs
Publication statusPublished - 2019 Jun 1

Fingerprint

Pyrazines
U937 Cells
Bearings (structural)
Small Molecule Libraries
Derivatives
Acylation
Halogens
Benzene
Condensation
Lymphoma
Screening
Substitution reactions
Therapeutics
3-hydroxybutanal

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Kim, Jinwoo ; Park, Mikyung ; Choi, Jiwon ; Singh, Dileep Kumar ; Kwon, Ho Jeong ; Kim, Seong Hwan ; Kim, Ikyon. / Design, synthesis, and biological evaluation of novel pyrrolo[1,2-a]pyrazine derivatives. In: Bioorganic and Medicinal Chemistry Letters. 2019 ; Vol. 29, No. 11. pp. 1350-1356.
@article{b161486933e9483a9cbdc309d3862d65,
title = "Design, synthesis, and biological evaluation of novel pyrrolo[1,2-a]pyrazine derivatives",
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.",
author = "Jinwoo Kim and Mikyung Park and Jiwon Choi and Singh, {Dileep Kumar} and Kwon, {Ho Jeong} and Kim, {Seong Hwan} and Ikyon Kim",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.bmcl.2019.03.044",
language = "English",
volume = "29",
pages = "1350--1356",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "11",

}

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 journalArticle

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 -