联芳基1,2,3,4-四氢异喹啉衍生物和构象灵活类似物的抗胶质瘤活性的发现。
Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues.
作者信息
Mohler Michael L, Kang Gyong-Suk, Hong Seoung-Soo, Patil Renukadevi, Kirichenko Oleg V, Li Wei, Rakov Igor M, Geisert Eldon E, Miller Duane D
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
出版信息
J Med Chem. 2006 Sep 21;49(19):5845-8. doi: 10.1021/jm060020x.
Cultured rat astrocytes and C6 rat glioma were used as a differential screen for a variety of 1,2,3,4-tetrahydroisoquinoline (THI) derivatives. Compound 1 [1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrochloride] selectively blocked the growth of C6 glioma leaving normal astrocytes relatively unaffected. The potential for clinical utility of 1 was further substantiated in human gliomas and other tumor cell lines. Preliminary SAR of this activity was characterized by synthesis and testing of several THI and conformationally flexible variants.
培养的大鼠星形胶质细胞和C6大鼠胶质瘤细胞被用作对多种1,2,3,4-四氢异喹啉（THI）衍生物的差异筛选模型。化合物1 [1-(联苯-4-基甲基)-1,2,3,4-四氢异喹啉-6,7-二醇盐酸盐] 选择性地阻断C6胶质瘤细胞的生长，而对正常星形胶质细胞相对无影响。化合物1在人类胶质瘤和其他肿瘤细胞系中的临床应用潜力得到了进一步证实。通过合成和测试几种THI及其构象灵活的变体，对该活性的初步构效关系进行了表征。
Zotero 插件