Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)

Park, Chun-Ho; Chun, Kwangwoo; Joe, Bo-Young; Park, Ji-Seon; Kim, Young-Chul; Choi, Ji-Soo; Ryu, Dong-Kyu; Koh, Seong-Ho; Cho, Goang Won; Kim, Seung Hyun; Kim, Myung-Hwa

doi:10.1016/j.bmcl.2010.02.014

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Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)

Park, Chun-Ho;
Chun, Kwangwoo;
Joe, Bo-Young;
Park, Ji-Seon;
Kim, Young-Chul;
... Koh, Seong-Ho;
... Kim, Seung Hyun;
외 4명

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14

초록

Highly potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1,2-dihydro-4H-thiopyrano[ 3,4-c]quinolin-5(6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC50 = 42 nM, ED50 = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.

키워드

Poly(ADP-ribose)polymerase PARP-1; Tricyclic derivatives; POLYMERASE-1 INHIBITORS; POTENT; DISCOVERY; DESIGN; CANCER

제목: Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1)

저자: Park, Chun-Ho; Chun, Kwangwoo; Joe, Bo-Young; Park, Ji-Seon; Kim, Young-Chul; Choi, Ji-Soo; Ryu, Dong-Kyu; Koh, Seong-Ho; Cho, Goang Won; Kim, Seung Hyun; Kim, Myung-Hwa

DOI: 10.1016/j.bmcl.2010.02.014

발행일: 2010-04

유형: Article

저널명: Bioorganic and Medicinal Chemistry Letters

권: 20

호: 7

페이지: 2250 ~ 2253