Synthesis and evaluation of thiopyrano[3,4-c]quinoline-9-carboxamide derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

Park, Chun-Ho; Chun, Kwangwoo; Joe, Bo-Young; Choi, Jong-Hee; Lee, Han-Chang; Ku, Il-Whea; Kim, Hyun Young; Koh, Seong-Ho; Cho, Goang Won; Kim, Seung Hyun; Kim, Myung-Hwa

doi:10.1007/s00044-011-9673-6

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Synthesis and evaluation of thiopyrano[3,4-c]quinoline-9-carboxamide derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

Park, Chun-Ho;
Chun, Kwangwoo;
Joe, Bo-Young;
Choi, Jong-Hee;
Lee, Han-Chang;
... Kim, Hyun Young;
... Koh, Seong-Ho;
... Kim, Seung Hyun;
외 3명

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4

초록

A series of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors, 5-oxo-2,4,5,6-tetrahydro-1H-thiopyrano[3,4-c]quinoline-9-carboxamide derivatives, were successfully synthesized and their PARP-1 inhibitory activity was evaluated. These compounds were prepared from carboxylic acid 7 and the appropriate amines, and a number of the synthesized compounds were found to have significant PARP-1 activity. Among them, 9m showed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC50 = 0.045 mu M, ED50 = 0.54 mu M). Molecular modeling studies confirmed the obtained biological results.

키워드

Poly(ADP-ribose)polymerase; PARP-1 inhibitor; Thiopyranoquinoline derivatives; CELL-DEATH; DNA-DAMAGE; CHEMOPOTENTIATION; TEMOZOLOMIDE; DISCOVERY; DEPLETION; NAD(+); CANCER; POTENT; SITE

제목: Synthesis and evaluation of thiopyrano[3,4-c]quinoline-9-carboxamide derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

저자: Park, Chun-Ho; Chun, Kwangwoo; Joe, Bo-Young; Choi, Jong-Hee; Lee, Han-Chang; Ku, Il-Whea; Kim, Hyun Young; Koh, Seong-Ho; Cho, Goang Won; Kim, Seung Hyun; Kim, Myung-Hwa

DOI: 10.1007/s00044-011-9673-6

발행일: 2012-08

유형: Article

저널명: Medicinal Chemistry Research

권: 21

호: 8

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