Ben Eduful

As part of SGC-UNC’s scaffold hopping strategy to identify new series of compounds active against CaMKK2, we recently submitted a select number of compounds differing in hinge-binder for CaMKK2 enzyme inhibition assay. The hinge-binders included thienopyridine, furopyridine, quinoline, thienopyrimidines, pyrimidine, N-methyl azaindoles and quinazoline, Figure 1. Others are azaindoles, triazolopyridazine, pyrazolopyridine, imidazopyridine etc. Figure 1: Read More …

In my last post, I reported a new synthetic route to our quinoline series, Scheme 1. The goal was to overcome prior synthetic challenges and to allow for rapid synthesis of many different analogs over a short period of time. Scheme 1: New synthetic route for generating quinoline analogs I have as a result generated large 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 …

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 …

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 …

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 …

BRSK2 Compounds NRF2 is a transcription factor that regulates the expression of antioxidant proteins and functions to protect against oxidative stress caused by inflammation. Under normal physiological conditions, NRF2 is degraded by KEAP1 and Cullin 3 (CUL3) through a process called ubiquitination (ubiquitin-dependent proteolysis). Following ubiquitination, it is transported to the proteasome where it is Read More …

I provide herewith my first post –  A short overview of my current projects. Research at the SGC-UNC involves the preparation of active chemical probes for understudied protein kinases with the ultimate goal of designing potent small molecule inhibitors as treatment for diseases such as cancer. Kinases play critical roles in cellular signaling which controls important Read More …