16778-09-9Relevant academic research and scientific papers
Triphenylbutanamines: Kinesin spindle protein inhibitors with in vivo antitumor activity
Wang, Fang,Good, James A. D.,Rath, Oliver,Kaan, Hung Yi Kristal,Sutcliffe, Oliver B.,MacKay, Simon P.,Kozielski, Frank
supporting information; experimental part, p. 1511 - 1525 (2012/04/10)
The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit Kiapp ≥ 10 nM and GI50 ≈ 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.
Triphenylmethylamides (TPMAs): Structure-activity relationship of compounds that induce apoptosis in melanoma cells
Palchaudhuri, Rahul,Hergenrother, Paul J.
supporting information; experimental part, p. 5888 - 5891 (2009/06/25)
Triphenylmethylamides (TPMAs) have been previously identified as compounds that arrest cells in the G1-phase of the cell cycle and induce apoptotic death in melanoma cell lines in culture. Here we report the synthesis of a series of TPMA derivatives, allo
