Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2

Bioorg Med Chem Lett. 2001 Jun 4;11(11):1401-5. doi: 10.1016/s0960-894x(01)00219-0.

Abstract

Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N(4)-(1-benzyl-1H-indazol-5-yl)-N(6),N(6)-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Division / drug effects
  • Disease Models, Animal
  • ErbB Receptors / antagonists & inhibitors*
  • Mice
  • Mice, SCID
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Quinazolines / therapeutic use
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • 4557 W
  • Antineoplastic Agents
  • GW 974 cpd
  • Pyrimidines
  • Quinazolines
  • ErbB Receptors
  • Receptor, ErbB-2