Molecules: You'd better learn to live with them.
Dutasteride is of the same class of drug as Propecia and Proscar - the so-called 5-alpha-reductase inhbitors. These inhibit the enzyme of this name from converting testosterone into dihydrotestosterone.
Interestingly, the class is useful for both prostate hyperplasia (proscar) and hair loss (propecia) - these two are the same molecule. Avodart, which has been approved for prostate hyperplasia, was in trials for hair loss awhile back, but these were since dropped.
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This may be a silly question, but in a molecule such as this, where there's a "floppy" looking bond (at the upper N), does the molecule fold up into different configurations like a protein would? Would that affect how the drug works in the body, or is there generally enough energy available to unkink it?
Posted by: Xerxes | February 28, 2008 10:38 AM
Hey Xerxes: The N you're talking about is involved in two interesting bonds; one is that it is next to a carbonyl, making it an amide. Amides (like in proteins) have some double bond character which makes the system planar. This is one way a protein maintains its structure. But here, the N is also bound to an aromatic ring (a very bulk one at that with the 2 CF3 groups). The lone pair electrons on the N will want to stay perpendicular to the plane of the benzene ring, too. I don't know which force will win (whether the electrons will choose to stay in line with the aromatic system or go towards the C=O bond) but it is likely somewhat rigid. Another factor is that the CF3 groups will not want to bump into anything, so the benzene ring will have to be oriented to avoid "steric clash."
This is a small molecule, and probably has limited mobility, and lacks the secondary structure that you refer to in proteins. Likely, this molecule binds to its target in one conformation.
I'd be interested to know the role of the aromatic ring on this drug, too, but I imagine that might require a crystal structure of it bound.
Posted by: Vince Noir | February 29, 2008 1:49 PM
Xerxes
Looks like that upper bond is an amide conjugated to a phenyl ring, so I'm guessing that it probably doesn't have much conformational freedom. However, as I understand it, most drugs are designed to not have too much floppiness so that the entropic loss of them binding their target doesn't completely kill their binding constant.
Posted by: As You Lean | February 29, 2008 4:42 PM