Bagley, Mark C, Baashen, Mohammed, Chuckowree, Irina, Dwyer, Jessica E, Kipling, David and Davis, Terence (2015) Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells. Pharmaceuticals, 8 (2). pp. 257-276. ISSN 1424-8247
![]() |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (1MB) |
Abstract
Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.
Item Type: | Article |
---|---|
Schools and Departments: | School of Life Sciences > Chemistry |
Subjects: | Q Science > QD Chemistry Q Science > QD Chemistry > QD0241 Organic chemistry |
Depositing User: | Mark Bagley |
Date Deposited: | 18 Jan 2016 09:04 |
Last Modified: | 02 Jul 2019 20:16 |
URI: | http://sro.sussex.ac.uk/id/eprint/59251 |
View download statistics for this item
📧 Request an updateProject Name | Sussex Project Number | Funder | Funder Ref |
---|---|---|---|
Alignment of Synthesis, Medicinal Chemistry and Structural Genomics to Accelerate (Strathclyde lead) | G0926 | EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL | RKES 115428 |
2012 Doctoral Training Grant (EPSRC) | G0942 | EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL | EP/K503198/1 |
Unset | Unset | BBSRC | BB/D524140/1 |
A combined genetic and small molecule approach to studying the role of the p38/MK2 stress signalling | G0931 | ESRC-ECONOMIC & SOCIAL RESEARCH COUNCIL | ES/G037205/1 |
Unset | Unset | Saudi Cultural Bureau | I398 |