Discovery of Antiglioma Activity of Biaryl 1,2,3,4-Tetrahydroisoquinoline Derivatives and Conformationally Flexible Analogues
Journal of Medicinal Chemistry2006Vol. 49(19), pp. 5845–5848
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Michael L. Mohler, Gyong-Suk Kang, Seoung‐Soo Hong, Renukadevi Patil, Oleg V. Kirichenko, Wěi Li, Igor M. Rakov, Eldon E. Geisert, Duane D. Miller
Abstract
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.
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