BREAST CANCER CELL GROWTH-INHIBITING ENZYME INHIBITORS, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF

摘要

Novel enzyme inhibitors for treatment of breast cancer combine the inhibition of enzymes that combat aggressive breast cell growth both synergistically and additively. Pyrido-annulated indoles developed act in a selectively inhibiting manner on the enzymes HER2 and/or Brk in the nanomolar to picomolar concentration range in screening more than 200 kinases of the human kinome. The enzyme inhibitors inhibit the growth of breast cancer cells in the nanomolar concentration range without exhibiting critical toxic effects. The derivatization at the 6-position of the 4-chloro-α-carboline is achieved without by-products and, similarly to the derivatization at the 4-position with the aniline derivatives, takes place at high purity with quantitative yields.

主权项

1. Breast cancer cell growth-inhibiting enzyme inhibitors, comprising functional pyrido-annulated indoles and pyrido pyrroles of general formula in which each of X and Y=C, or X=C and Y=N or X=N and Y=C, and in which Z=NH, and wherein R1=Ph-3- or 4-CONH-R3 or 4-halogen or 4-OBn, —CN, —Cl, —Br, —F (-halogen), —OH, —CH3, —OCH3, —OC2H5, —OBn (-Oalkyl), —CF3, —NO2, —NH2, —NHCO alkyl, —SCH3; Ph-3- and 4-CONH-R3 or 4-halogen or 4-OBn, —CN, —Br, —F (-halogen), —OH, —CH3, —OCH3, —OC2H5 (-Oalkyl), —CF3, —NO2, —NH2, —NHCO alkyl, —SCH3 R2=Br (-halogen), NO2, NH2 R3=H, Br (halogen), heteroaryl, NH2, NHR4, NO2, CN, COOR4, NHSO2R4, NHCOR4, NHCOOR4, NHCONHR4, COalkyl, SO2NHR4, NHCONR5R6, SO2NR5R6 R4=alkyl, aminoalkyl, piperazinoalkyl, N-morpholinoalkyl, hydroxyalkyl R5, R6=alkyl; —CH2—CH2-T-CH2—CH2—, T=O, NH, NR4.