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

  • J Med Chem. 2006 Sep 21;49(19):5845-8. doi: 10.1021/jm060020x.
Michael L Mohler  1 ,  Gyong-Suk Kang ,  Seoung-Soo Hong ,  Renukadevi Patil ,  Oleg V Kirichenko ,  Wei Li ,  Igor M Rakov ,  Eldon E Geisert ,  Duane D Miller
Affiliations
  • 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
PMID: 16970409 DOI: 10.1021/jm060020x
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.