Author/Authors :
Mark G. Saulnier، نويسنده , , David B. Frennesson، نويسنده , , Mark D. Wittman، نويسنده , , Kurt Zimmermann، نويسنده , , Upender Velaparthi، نويسنده , , David R. Langley، نويسنده , , Charles Struzynski، نويسنده , , Xiaopeng Sang، نويسنده , , Joan Carboni، نويسنده , , Aixin Li، نويسنده , , Ann Greer، نويسنده , , Zheng Yang، نويسنده , , Praveen Balimane، نويسنده , , Marco Gottardis، نويسنده , , Ricardo Attar، نويسنده , , Dolatrai Vyas، نويسنده ,
Abstract :
A series of IGF-1R inhibitors is disclosed, wherein the (m-chlorophenyl)ethanol side chain of BMS-536924 (1) is replaced with a series of 2-(1H-imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chains. Some analogs show improved IGF-1R potency and oral exposure. Analogs from both series, 16a and 17f, show in vivo activity comparable to 1 in our constitutively activated IGF-1R Sal tumor model. This may be the due to the improved protein binding in human and mouse serum for imidazole 16a and the excellent oral exposure of pyrazole 17f.
Keywords :
IGF-1R , Tyrosine kinases , Benzimidazole , Haloimidazole , Halopyrazole , Anticancer agent
