bms-536924 and benzimidazole

bms-536924 has been researched along with benzimidazole* in 1 studies

Other Studies

1 other study(ies) available for bms-536924 and benzimidazole

Article	Year
Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one. Bioorganic & medicinal chemistry letters, 2010, May-15, Volume: 20, Issue:10 A series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure-activity and structure-solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating the basicity of distal nitrogen with appropriate substitutions. Topics: Administration, Oral; Animals; Benzimidazoles; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Humans; Mice; Mice, Nude; Piperazines; Protein Kinase Inhibitors; Pyridones; Rats; Receptor, IGF Type 1; Structure-Activity Relationship; Xenograft Model Antitumor Assays	2010

Article

Year

Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one.

Bioorganic & medicinal chemistry letters, 2010, May-15, Volume: 20, Issue:10

A series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure-activity and structure-solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating the basicity of distal nitrogen with appropriate substitutions.

Topics: Administration, Oral; Animals; Benzimidazoles; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Humans; Mice; Mice, Nude; Piperazines; Protein Kinase Inhibitors; Pyridones; Rats; Receptor, IGF Type 1; Structure-Activity Relationship; Xenograft Model Antitumor Assays

2010