- Manufacturing method of piperidinyl sulfonyl sulfonamide
-
The present invention relates to the preparation of diphenylsulfonylamide represented by formula 1. Chemically 1 _AOMARKENCODEGTX06017. A compound represented by chemical formula 2 is obtained by reacting a compound represented by chemical formula 3 with N-protected piperidine amine to obtain a compound represented by the following formula, wherein N is protected with N-protected piperidine amine to obtain a compound represented by chemical formula 4 6, and to obtain a compound represented by the 6 7 formula 5 of the compound represented by the following general formula in the following 7 chemical formula 5 to obtain a compound represented by the following general formula (1 I). AOMARKENCODELTX017. Chemically 2 _AOMARKENCODEGTX06017. AOMARKENCODELTX017. Chemically 3 _AOMARKENCODEGTX06017. AOMARKENCODELTX017. Chemically 4 _AOMARKENCODEGTX06017. AOMARKENCODELTX017. Chemically 5 _AOMARKENCODEGTX06017. AOMARKENCODELTX017. Chemically 6 _AOMARKENCODEGTX06017. AOMARKENCODELTX017. Chemically 7 _AOMARKENCODEGTX06017.
- -
-
Paragraph 0053-0057
(2021/01/29)
-
- Synthesis and biological evaluation of optimized inhibitors of the mitotic kinesin Kif18A
-
The mitotic spindle, a highly dynamic structure composed of microtubules, mediates the segregation of the previously duplicated genome into the two nascent daughter cells. Errors in this process contribute to pathology including tumor formation. Key for the shape and function of the mitotic spindle are kinesins, molecular motor proteins that convert chemical energy into mechanical work. Due to their fast mode of action, small molecules are valuable tools to dissect the dynamic functions of kinesins during mitosis. In this study, we report the identification of optimized small molecule inhibitors of the mitotic kinesin Kif18A. Using BTB-1, the first identified Kif18A inhibitor, as a lead compound, we synthesized a collection of derivatives. We demonstrate that some of the synthesized derivatives potently inhibited the ATPase activity of Kif18A with a half maximal inhibitory concentration (IC50) value in the low micromolar range. In vitro analysis of a panel of Kif18A-related kinesins revealed that the two most potent compounds show improved selectivity compared to BTB-1. Structure-activity relationship studies identified substituents mediating undesired inhibitory effects on microtubule polymerization. In summary, our study provides key insights into the mechanism of action of BTB-1 and its analogs, which will have a great impact on the further development of highly selective and bioactive Kif18A inhibitors. Since Kif18A is frequently overexpressed in solid tumors, such compounds are not only of great interest for basic research but also have the potential to open up new strategies for the treatment of human diseases.
- Braun, Joachim,M?ckel, Martin M.,Strittmatter, Tobias,Marx, Andreas,Groth, Ulrich,Mayer, Thomas U.
-
p. 554 - 560
(2015/04/21)
-
- Modulation of Wnt signaling through inhibition of secreted frizzled-related protein i (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides
-
The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic a
- Moore, William J.,Kern, Jeffrey C.,Bhat, Ramesh,Commons, Thomas J.,Fukayama, Shoichi,Goljer, Igor,Krishnamurthy, Girija,Magolda, Ronald L.,Nogle, Lisa,Pitts, Keith,Stauffer, Barb,Trybulski, Eugene J.,Welmaker, Gregory S.,Wilson, Matthew,Bodine, Peter V. N.
-
experimental part
p. 105 - 116
(2009/08/07)
-
- PIPERIDINYL ARYLSULFONE DERIVATIVES AS MODULATORS OF SECRETED FRIZZLED RELATED PROTEIN-1
-
Compounds of Formula (1), or pharmaceutically acceptable salts thereof, are provided: which are modulators of secreted frizzled related protein- 1. The compounds, and compositions containing the compounds, can be used to treat a variety of disorders, including osteoporosis.
- -
-
Page/Page column 18
(2008/12/05)
-
- 2H-Benzimidazoles (Isobenzimidazoles). Part 3. Thermal Isomerisation of Substituted 2H-Benzimidazoles to 1H-Benzimidazoles
-
2H-Benzimidazole-2-spirocyclohexanes (1) when heated undergo a 1,5-sigmatropic rearrangement to 2,3-disubstituted 1H-benzimidazoles.A decided effect on the direction of this isomerisation was observed with substituents in the homodiene ring.
- Herbert, John A. L.,Iddon, Brian,Robinson, Andrew G.,Suschitzky, Hans
-
p. 991 - 998
(2007/10/02)
-