含非芳酰胺的三环衍生物的合成与评价作为聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。
Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1).
机构信息
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.
出版信息
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2250-3. doi: 10.1016/j.bmcl.2010.02.014. Epub 2010 Feb 8.
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 (IC(50) = 42 nM, ED(50) = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.
我们合成了具有非芳环 A 环的 9-羟基-1,2-二氢-4H-噻吩并[3,4-c]喹啉-5(6H)-酮衍生物等强效多聚（ADP-核糖）聚合酶-1（PARP-1）抑制剂。在这些衍生物中，12a 表现出低纳摩尔的酶和细胞活性（IC50 = 42 nM，ED50 = 220 nM），同时具有良好的水溶性。此外，12a 在体外具有良好的微粒体稳定性和体内脑渗透性。
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