462630-41-7Relevant articles and documents
HR22C16: A potent small-molecule probe for the dynamics of cell division
Hotha, Srinivas,Yarrow, Justin C.,Yang, Janet G.,Garrett, Sarah,Renduchintala, Kishore V.,Mayer, Thomas U.,Kapoor, Tarun M.
, p. 2379 - 2382 (2003)
A high-throughput, microscopy-based chemical-genetic screen identified HR22C16, which causes a monoastral mitotic block, as a small-molecule probe for cell division (see picture). By using a diastereoselective, traceless solid-phase synthesis and biological assays, a more potent HR22C16 analogue was then identified. A photocaging strategy for HR22C16 was also developed to allow fast temporal control over the function of the target protein Eg5.
A general strategy for the highly stereoselective synthesis of HR22C16-like mitotic kinesin Eg5 inhibitors from both l- and d-tryptophans
Dong, Jing,Trieu, Tien Ha,Shi, Xiao-Xin,Zhang, Qiang,Xiao, Sen,Lu, Xia
, p. 1865 - 1873 (2012/01/05)
An efficient and general strategy for the highly stereoselective synthesis of HR22C16-like mitotic kinesin Eg5 inhibitors 1 from both l- and d-tryptophan methyl ester hydrohalides is described. (1R,3S)-trans-1,3-Disubstituted 1,2,3,4-tetrahydro-β-carbolines (1R,3S)-trans-2 could be obtained in high yields and with high stereoselectivities from the Pictet-Spengler reaction of l-tryptophan methyl ester hydrohalide with some 3-acyloxyl benzaldehydes via a CIAT (crystal induced asymmetric transformation) process, whereas (1R,3R)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines (1R,3R)-cis-2 could also be obtained in high yields and with high stereoselectivities from a Pictet-Spengler reaction of d-tryptophan methyl ester hydrohalide with some other 3-acyloxyl benzaldehydes via a CIAT process. Both compounds (1R,3S)-trans-2 and (1R,3R)-cis-2 were efficiently converted into HR22C16-like mitotic kinesin Eg5 inhibitors 1 by the same one-pot procedure through tandem reactions. A total of eighteen target compounds 1 were obtained from six intermediate compounds 2 in 87-95% yields.
Synthesis and biological evaluation of functionalised tetrahydro-β- carboline analogues as inhibitors of Toxoplasma gondii invasion
Walton, Jeffrey G. A.,Patterson, Stephen,Liu, Gu,Haraldsen, Jeralyn D.,Hollick, Jonathan J.,Slawin, Alexandra M. Z.,Ward, Gary E.,Westwood, Nicholas J.
supporting information; experimental part, p. 3049 - 3060 (2011/02/25)
Techniques for the identification of the protein target(s) of small molecules are proving very important following an increase in the use of phenotype-based screening in chemical biology and drug discovery. One approach, known as the yeast-3-hybrid approach, has shown considerable potential. A key factor in the success of this approach is the preparation of a complex molecule referred to as a chemical inducer of dimerisation (CID). The synthesis of two CIDs based on a bioactive tetrahydro-β-carboline core structure is reported and evidence presented that shows the CIDs are of utility in this approach. A series of chemo- and bioinformatic studies coupled with SAR development inspired the choice of CIDs.
