Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1) |
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| Authors: | Chun-Ho Park Kwangwoo Chun Bo-Young Joe Ji-Seon Park Young-Chul Kim Ji-Soo Choi Dong-Kyu Ryu Seong-Ho Koh Goang Won Cho Seung Hyun Kim Myung-Hwa Kim |
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| Affiliation: | 1. Drug Discovery Laboratory, R&D Center, Jeil Pharmaceutical Co., Ltd. 117-1, Keungok-Ri, Baekam-Myun, Cheoin-Gu, Yongin-City, Kyunggi-Do 449-861, Republic of Korea;2. Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea;3. Department of Biotechnology, Yonsei University, Seodaemun-Gu, Seoul 120-740, Republic of Korea |
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| Abstract: | 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. |
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