1235893-58-9Relevant academic research and scientific papers
8-THP-DHI analogs as potent Type I dual TIE-2/VEGF-R2 receptor tyrosine kinase inhibitors
Hudkins, Robert L.,Zulli, Allison L.,Underiner, Ted L.,Angeles, Thelma S.,Aimone, Lisa D.,Meyer, Sheryl L.,Pauletti, Daniel,Chang, Hong,Fedorov, Elena V.,Almo, Steven C.,Fedorov, Alexander A.,Ruggeri, Bruce A.
scheme or table, p. 3356 - 3360 (2010/08/07)
A novel series of 8-(2-tetrahydropyranyl)-12,13-dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazoles (THP-DHI) was synthesized and evaluated as dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors. Development of the structure-activity relationships (SAR) with the support of X-ray crystallography led to identification of 7f and 7g as potent, selective dual TIE-2/VEGF-R2 inhibitors with excellent cellular potency and acceptable pharmacokinetic properties. Compounds 7f and 7g were orally active in tumor models with no observed toxicity.
