How important is small molecule structure determination for drug development and discovery?
Very. Let’s say you have a compound that does something amazing to your cell culture. You know the structure, and have a pretty good idea how it binds to its target receptor, and the pharmacological mechanism(s) responsible for its amazing effects. Before you can consider this lead compound a drug candidate, you have to consider a few things, including (but not limited to):
Solubility - What kind of vehicle are you going to use to administer this compound? Good drug candidates are frequently poorly soluble in saline, but DMSO can be toxic.
Bioavailability - When administered via injection will it distribute into tissues, or get stuck on plasma proteins and never make it out of the blood stream?
BBB permeability - Will it cross the blood-brain-barrier? Sometimes the answer you want is yes, sometimes it’s no.
Off-target interactions - What are the chances this compound might preferentially bind to say, potassium channels? That wouldn’t be good.
Metabolites - Might they be toxic? How about bioactive?
Route of administration - Turns out that humans don’t like getting shots. People much prefer pills. Is the compound something that could be absorbed through the GI tract?
Anyway, good drug candidates frequently have structures designed to address these and other issues.