Hits expansion (1st, 2nd, and after reconsidering bleaching compounds) of RA-0010874

[qxsml]

1st expansion:

Da confirmed that RA-0010874 is not assay interfering while the compounds with substitutions on the quinoline ring are. Therefore, a few more compounds were planned to synthesize with modification on the triazole ring: the following compounds have been synthesized with clean LCMS: I resynthesized RA-0010874 because the previous tested batch was purchased, and testing my synthesized batch and check whether it is bleaching in TAMU's bleaching assay is helpful.

Both UCL and TAMU are developing a gel-based assay, therefore I have ~2 weeks to crank out a few more compounds for testing, below are the candidates using department available starting materials, I will synthesize as many as I can.

[qxsml]

The following compounds have been synthesized over the past two weeks, with the exception of the molecule labeled in red. I was unable to identify a major product spot for this molecule, and the minor spots I isolated did not produce a correct MS. Generally, these compounds, which have no substitutions on the quinoline ring, are much easier to synthesize than the ones with hydroxyl group because they typically do not have solubility issues in common organic solvents. All of them have been confirmed to have pure and correct LCMS. And I just finished H NMR analysis. They will be shipped to TAMU and DKU next week, and the process of weighing the solid fractions, including (the compounds synthesized and reported above) is currently ongoing.

[qxsml]

The compounds synthesized in the second expansion were registered. They were shipped in solid form to TAMU and DKU respectively. . These compounds (as 10 mM DMSO solution), including 7 compounds that showed activity in the first expansion were send to Wenjie at UCL for testing in Gel-based assay.

[qxsml]

Results of testing in the gel assay from Wenjie at UCL: Relative inhibition compared to benzopurpurine unless otherwise indicated. Non-colored compounds show no inhibition:

SAR based on the results: