462630-41-7Relevant academic research and scientific papers
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.
Highly diastereoselective crystallization-induced asymmetric transformation of 1,3-disubstituted-tetrahydro-β-carbolines in water
Meng, Tian-Zhuo,Shi, Xiao-Xin,Qu, Hui-Ya,Zhang, Yi,Huang, Zhong-Shou,Fan, Qi-Qi
, p. 47753 - 47757 (2017/10/18)
A green and highly stereoselective method for the synthesis of cis or trans-1,3-disubstituted-tetrahydro-β-carbolines has been developed using water as the solvent. A mixture of cis and trans-1,3-disubstituted-tetrahydro-β-carboline hydrochlorides can be converted to a single cis or trans isomer via a crystallization-induced asymmetric transformation process. It is possible to get both isomers using this method by incorporating different additives in water. This method has advantages such as environmental friendliness, high stereoselectivity, suitability for industrialization, and non-toxicity.
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
experimental part, 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.
The first highly stereoselective approach to the mitotic kinesin Eg5 inhibitor HR22C16 and its analogues
Xiao, Sen,Shi, Xiao-Xin
experimental part, p. 226 - 231 (2010/05/02)
A general method for the synthesis of the mitotic kinesin Eg5 inhibitor HR22C16 1 and its analogues based on protecting group (PG)-modulated highly diastereoselective Pictet-Spengler reaction of l-tryptophan methyl ester hydrochloride with meta-(RO)-benzaldehyde is described. By using the enantiomerically pure (1R,3S)-1,3-disubstituted tetrahydro-β-carboline trans-4c as a common chiral synthon, HR22C16 1 and its analogues 2 and 3 were synthesized in 90.1%, 90.2%, and 86.5% overall yields, respectively.
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.
Kinesin inhibitors
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Page 13;14;Sheet 11, (2008/06/13)
The present invention provides for compounds, compositions, methods and systems for inhibiting cell growth. More specifically, the present invention provides for methods, compounds and compositions which are capable of inhibiting mitosis in metabolically active cells. Compounds, compositions and methods of the present invention inhibit the activity of a protein involved in the assembly and maintenance of the mitotic spindle. One class of proteins which acts on the mitotic spindle is the family of mitotic kinesins, a subset of the kinesin superfamily.
Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5
Sunder-Plassmann, Nils,Sarli, Vasiliki,Gartner, Michael,Utz, Mathias,Seiler, Jeanette,Huemmer, Stefan,Mayer, Thomas U.,Surrey, Thomas,Giannis, Athanassios
, p. 6094 - 6111 (2007/10/03)
The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it
