Remaining Data Needed for OHOH Compound(s)

[mattodd]

The frontrunner OHOH compound (OSM-S-556, MMV1581295) has, despite some issues to do with consistency of potency (#59) been shown to be active. Its activity is not too surprising given the SAR around this structure - i.e. it's not a surprising singleton. This molecule is likely to possess good solubility. It's time we measured that solubility as well as the microsomal/hepatic clearance. If the data are good, the molecule would have significant promise and be a candidate for in vivo evaluation. Either way this can act as a punchline for the first Series 4 paper.

We need to send a sample to Sue Charman's lab for measurement of the same data types as we obtained for the last set, and we'll need to secure clearance for that measurement from the folks at MMV. (note that mouse liver microsomes are perhaps suboptimal for us, and that rat is better because rat is the PK model organism usually used, but I would suggest we look at MLM for consistency with previous data (to help with publication) and anyway it's rat hepatocytes that are used).

Unless there are thoughts to the contrary I'll ask @mbhebhe to dig out the latest sample (batch DGS 81-1 I think, but this needs to be noted), check the NMR spectrum and ship it (provided we have approval to do so).

Note that the difluoro analog OSM-S-560 (MMV1581298) could also be measured. It came back as much less potent (batch DGS77-1) in #65 but could be sent at the same time. Probably a useful second datapoint.