Anticancer activity of (1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and -purines against the MCF-7 cell line: Preliminary cDNA microarray studies

Bioorg Med Chem Lett. 2008 Feb 15;18(4):1457-60. doi: 10.1016/j.bmcl.2007.12.070. Epub 2008 Jan 1.

Abstract

Completing a SAR study, a series of (RS)-1- or 3-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H- or 9H-purines have been prepared. Their antiproliferative activities on MCF-7 cells are here presented and discussed. (RS)-6-Chloro-9-[1-(9H-9-fluorenylmethoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-9H-purine (28) is the most active (IC(50)=0.67+/-0.18 microM) of the series so far described. cDNA microarray technology reveals potential drug targets, which are mainly centred on apoptosis regulatory pathway genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals / chemistry
  • Acetals / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Humans
  • Inhibitory Concentration 50
  • Oligonucleotide Array Sequence Analysis
  • Oxazepines / chemistry*
  • Oxazepines / pharmacology*
  • Purines / pharmacology*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Acetals
  • Antineoplastic Agents
  • Oxazepines
  • Purines
  • Pyrimidines