My mention of hardly ever taking an optical rotation led into the question of what to do about chirality in drug candidates. One commentor mentioning hearing someone from one company making a big deal out of including chiral fragments in their molecules, which seemed to contradict my attitude.
It sure does - but I'm right. Well, on this issue I am, anyway. Chirality can be a great help, but it's often purchased at a great price. It's true that our molecules are interacting with chiral protein binding sites, which should mean that the right optically active compound is probably the best fit you can get. But how long will it take you to get there, and what are you willing to pay?
There are chiral centers and there are chiral centers, of course. The ideal situation is a single chiral carbon that you buy from a cheap source (a naturally occurring amino acid, say) which quickly gets turned into something non-epimerizable. That's not so painful, and if it buys you better activity, then why not? Compare that to the other end of the deal, which might be something that can't be purchased cheaply and requires a from-the-ground-up chiral synthesis. It's either that or a good old fashioned resolution, which means that half your work and money has to be thrown away. Throw in some chances of racemization and you're looking at a real campaign, which you'd better have a good reason to embark on.
Other things being equal, I try to avoid chirality. There are plenty of achiral compounds out there that have earned billions of dollars, after all, so why go looking for trouble? If I add a chiral center, I try to make it something that's available cheaply, not some exotic creature-from-the-chiral-lagoon stuff that goes for a dollar a milligram on the easier enantiomer. There's almost always something else you could be doing rather than going down that path.
Still, I'm pretty sure that the number of chiral drugs (outside of natural products) has been increasing over time, although I'd like to know just how much. I'm not sure that I believe the chart here, for example, and I'd like to split out the cases where someone comes in selling a single enantiomer of a formerly racemic compound. But newer reactions are putting more and more chiral chemical space into the "worth a try" category. So I don't fear handedness in my compounds - but I don't seek it out, either. If that interviewer from Company X really does, well, my achiral compounds and I will just watch from a safe distance.