Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.

Literature DB >> 16439123

Kinesin spindle protein (KSP) inhibitors. Part 2: the design, synthesis, and characterization of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP.

Mark E Fraley¹, Robert M Garbaccio, Kenneth L Arrington, William F Hoffman, Edward S Tasber, Paul J Coleman, Carolyn A Buser, Eileen S Walsh, Kelly Hamilton, Christine Fernandes, Michael D Schaber, Robert B Lobell, Weikang Tao, Victoria J South, Youwei Yan, Lawrence C Kuo, Thomayant Prueksaritanont, Cathy Shu, Maricel Torrent, David C Heimbrook, Nancy E Kohl, Hans E Huber, George D Hartman.

Abstract

The evolution of 2,4-diaryl-2,5-dihydropyrroles as inhibitors of KSP is described. Introduction of basic amide and urea moieties to the dihydropyrrole nucleus enhanced potency and aqueous solubility, simultaneously, and provided compounds that caused mitotic arrest of A2780 human ovarian carcinoma cells with EC(50)s<10nM. Ancillary hERG activity was evaluated for this series of inhibitors.

Entities: Chemical Disease Gene

Mesh：

Substances：
Pyrroles
Kinesin

Year: 2006 PMID： 16439123 DOI： 10.1016/j.bmcl.2006.01.030

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

Keyword Cloud
Cited

11 in total

1. Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core.

Authors: Elizabeth D Kim; Rebecca Buckley; Sarah Learman; Jessica Richard; Courtney Parke; David K Worthylake; Edward J Wojcik; Richard A Walker; Sunyoung Kim
Journal: J Biol Chem Date: 2010-03-18 Impact factor: 5.157

2. Docking studies on kinesin spindle protein inhibitors: an important cooperative 'minor binding pocket' which increases the binding affinity significantly.

Authors: Cheng Jiang; Yadong Chen; Xiaojian Wang; Qidong You
Journal: J Mol Model Date: 2007-06-23 Impact factor: 1.810

3. ADMET evaluation in drug discovery. 12. Development of binary classification models for prediction of hERG potassium channel blockage.

Authors: Sichao Wang; Youyong Li; Junmei Wang; Lei Chen; Liling Zhang; Huidong Yu; Tingjun Hou
Journal: Mol Pharm Date: 2012-03-16 Impact factor: 4.939

4. Pathway of ATP hydrolysis by monomeric kinesin Eg5.

Authors: Jared C Cochran; Troy C Krzysiak; Susan P Gilbert
Journal: Biochemistry Date: 2006-10-10 Impact factor: 3.162

5. 3D-QSAR studies of dihydropyrazole and dihydropyrrole derivatives as inhibitors of human mitotic kinesin Eg5 based on molecular docking.

Authors: Xingyan Luo; Mao Shu; Yuanqiang Wang; Jin Liu; Wenjuan Yang; Zhihua Lin
Journal: Molecules Date: 2012-02-17 Impact factor: 4.411

Review 6. Kinesin-5: cross-bridging mechanism to targeted clinical therapy.

Authors: Edward J Wojcik; Rebecca S Buckley; Jessica Richard; Liqiong Liu; Thomas M Huckaba; Sunyoung Kim
Journal: Gene Date: 2013-08-14 Impact factor: 3.688

7. Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex.

Authors: David R Calabrese; Xiang Chen; Elena C Leon; Snehal M Gaikwad; Zaw Phyo; William M Hewitt; Stephanie Alden; Thomas A Hilimire; Fahu He; Aleksandra M Michalowski; John K Simmons; Lindsey B Saunders; Shuling Zhang; Daniel Connors; Kylie J Walters; Beverly A Mock; John S Schneekloth
Journal: Nat Commun Date: 2018-10-12 Impact factor: 14.919