Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues.

MichaelL Mohler, Gyong-Suk Kang, Seoung-Soo Hong, Renukadevi Patil, OlegV Kirichenko, Wei Li, IgorM Rakov, EldonE Geisert, DuaneD Miller

Index: J. Med. Chem. 49 , 5845-8, (2006)

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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.