All Analogs Evaluated to Date
Index of all Series 3 compounds and Master List of all OSM compounds (can filter on Series 3) <-- There is a chance that not all Series 3 compounds are in the Master List.
(as of early 2019 - raw files are available in this repo for editing)
Compound OSM-S-106 is the original hit, and easily the most active. The top row of compounds are the only analogs evaluated to date that possess any activity. All others are inactive. Molecules OSM-S-72 to OSM-S-80 are commercially available molecules.
Changing the C-6 substituent to H, Br, Ph or a selection of para-substituted phenyls kills activity (OSM-S-71, 123, 128-132, 134, 139). Replacing the amino group at C-4 with a morpholine group kills activity (OSM-S-117, 124-127). Replacing the meta-sulfonamide with an amide also killed activity (OSM-S-132-135, 142).
The synthesis of OSM-S-137 was inspired by another molecule found in the TCAMS data set: TCMDC-132385 was found to display activity of 1.015 uM. The team postulated that substituting the C-6 phenyl group in TCMDC-132385 with the benzene sulfonamide (as per OSM-S-106) would lead to increased activity, but the activities were comparable. Replacing the amino group at C-4 with a substituted piperazine can retain some activity.
TF16-1, 17-1, 18-1 were designed to give insight into the importance of the hydrogen donor extending from the meta-position of the C-6 aryl group. TF7-1 and TF8-1 probed the addition of an extra H-bond donor. Both these changes killed activity.
Some solubility issues were flagged in previous rounds of testing for the aminothienopyrimidines. This was surprising owing to the favourable CLogP values calculated for the compounds. Upon suggestion PT22, TF3-1, TF4-1 were synthesised to include a bulky group in the ortho-position to deplanarise the core which should increase water solubility (Ref). Unfortunately, these compounds proved inactive and derivatives of them were not pursued any further.
All the other molecules were intermediates to the final products and they too were not potent.
May 2022: a selection of SAR data highlighting a few key features discovered to date.
Results from the November/December 2018 S3 screen (all novel compounds in this screen were inactive):
Results from 2023 (all novel compounds were inactive):
