A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
In a collaboration between SGC-University of North Carolina-Chapel Hill and M4K Pharma, we plan to synthesize 3 different imidazopyridin pyrazines as promiscuous kinase ALK2 inhibitors, compounds 1-3, Scheme 1. The first step will be the synthesis of key intermediate 10, Scheme 2. The proposed synthesis begins with a nucleophilic aromatic substitution on compound 4 to Read More …
We have received some very interesting biological data for our CaMKK2 inhibitor series (furopyridine, Azaindole and quinoline) and I will be sharing the data in the coming weeks, but before that, I wanted to share my synthetic efforts towards our quinoline series. Initial synthesis of quinoline analogs: Starting with 6-Bromo-4-chloroquinoline, a two (2) step synthetic Read More …
At SGC we are interested in developing protein kinase inhibitors with a high selectivity towards other protein kinases. Based on lead compounds from the literature and our group new and selective CDKL2 inhibitors should be designed, synthesized and tested. Carla Alamillo, a former member of our group, worked on this topic and mentioned in her Read More …
Continuing with the line of delivering a chemical probe for DRAK2/STK17B kinase, we decided to revise the procedure to synthesize analogs with a thieno[2,3-d]pyrimidine core, which are intended to be used as negative control in our DRAK2 inhibition study. We shortened the synthesis of these pyrimidines to 2 steps from the starting material 6-bromo-4-chlorothieno[2,3-d]pyrimidine 1 Read More …
The line up of inhibitor series (hinge binders) for CaMKK2 currently being pursued include: furopyridine, azaindole (pyrrolopyridine), quinoline, triazolopyridazine, imidazopyrazine, pyrazolopyrimidine. Figure 1. Figure 1: CaMKK2 hinge binders As part of our structure and activity relationships (SAR), we continue to build diversity on the pyridine ring for the furopyridine series, and new compounds added to Read More …
The goal of the Structural Genomics Consortium (SGC) is to discover and share selective small molecule inhibitors of protein kinases. Kinases have key roles in cell signaling, regulation of cell cycle progression, metabolism and other significant biological function. Cancers, immunological and metabolic diseases, among other ailments are caused by deregulation of kinase function. Protein kinases Read More …
Following the successful synthesis of the furopyridine scaffold via an alternative synthetic route, conditions have been worked out to optimize yields on the synthesis of the key intermediate: 5-bromobenzofuran-3(2H)-one. Thus far the following set of analogs, Figure 1, have been generated by building diversity on the pyridine ring. These analogs together with with proposed others Read More …
This is what is planned to be the last small set of compounds prepared as STK17B/DRAK2 kinase inhibitors. Here, chemical modifications are made in the “top part” of the parent compound AP-39. The goal is to evaluate the role of other functional groups such as imidazole, tetrazole, and sulfonamides (1-3). Other changes include replacement of Read More …
Preparation of CaMKK2 analogs Pursuant to our aim of preparing a library of small molecule chemical probes around our most promising core scaffold, furopyridine, we sought to develop different chemistries that would allow us to achieve this objective. In the original synthetic route, 5-bromofuro[2,3-b]pyridine, 1, was able to undergo the Suzuki cross-coupling reaction to install Read More …
The original compound donated by Pfizer PFE-PKIS 43 (thienopyrimidine scaffold), showed activity against 3 kinases greater than 70% inhibition in the KinomeSCAN at 1 µM (STK17B/DRAK2, AURKB and SRPK2). In the series of compounds recently synthesized as thienopyrimidine derivatives we seek selective and potent inhibitors for STK17B/DRAK2 only. To further identify off-target activity of these Read More …
