h a l f b a k e r yContrary to popular belief
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heptacyclic pharmaceutical motif
swapping out a <=> benzene with a heptacyclic shape across all categories of preapproved drugs to create a beneficial change with quantified risk that permits FDA rapid approval | |
A few years ago the FDA decided that chiral versions of a drug could be considered different drugs yet the fact that the blend of chiral forms had been preapproved gave them the ability to grant wide approval to specific chiral versions absent much further testing.
This made a big difference as frequently
the pure chiral forms were much more active with a different effect profile.
I suggest a similar opportunity, at a multicyclic molecule use the change from a benzene to a heptene or pentene as the basis to create variations of all the thousands of approved pharmaceuticals. Among numerous effects, rather like setting a compass to a slightly different angle, the receptor active functional groups will be splayed slightly differently creating different receptor fit.
That slight angle difference will create effectiveness variation yet possibly along bounds of likelihood. Thus a researcher or FDA approver could predict likelihood of similarity of risk, permitting much more rapid approval of the new drugs.
There is another benefit as well, fine adjustment. Compare the tremendous difference of a -H, -OH, -CH3 on a molecule, it is possible that meaningful pharmaceutical effects come from the areas between these large chunks of variation which would be a benefit of compass perspective heptacyclization.
Its a way to create potentially more effective antibiotics, anticancer, as well as new varieties of cardiovascular medications at a supernumerous rate while minimizing or at least quantifying risk.
Um, is such a simple idea actually new
heptacyclic natural pharmaceuticals as well as functional group variants are slightly known, pubmed lists just 39 papers. Apparently this is the first suggestion of comprehensively swapping out 6 cycle shapes with 7 cycle shapes at molecules of proven benefit to see what happens. This is a way to proliferate new pharmaceuticals of any kind with less risk and effort per developed new drug.
Translation:
Changing a 6cycle shape to a 7 cycle shape makes those OH n Methyl groups branch out slightly differently making them differently effective yet at fairly similar risk. Apply that to all the known drugs, screen to find supereffective versions. Perhaps computer models could find those with the most likely to be more effective at less risk.
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There are two issues: effectiveness and
approvability. For effectiveness, drug companies
will usually try many minor variations on molecular
structure (this may also have the benefit of
gaining or extending a patent, since it's a new
molecule). If they don't routinely try changing
ring-sizes, my guess is that it's because it's
difficult to do (synthetically) or hasn't proven to
be effective. |
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For approval, I'm not sure if a 7-ring version of
a 6-ring compound would fly through in
the same way that pure chiral forms did. If I
understand your argument, pure chiral forms were
pre-approved for safety because both enantiomers
had already been approved as a combination. In
the case of a new ring-size, you're dealing with a
compound which has probably never been tested
before, and (I imagine) would still need full
testing. |
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(On the same topic, I do believe that we need to
very, very dramatically shorten drug evaluation
and approval times, as long as recipients
understand and accept the increased risk. For
some drugs, the long approval period may save
lives, but is equally likely to cost more lives in
terms of delayed treatments. ) |
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Problem-
The Chiral thing is based on the fact that both were already present in the drug (a simple fact of chemical production). Since they were already present in low quantities they were known to be safe, if not effective. This meant that the FDA didn't require testing for safety. |
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A seven ring in place of a six is not already present in the manufactured drug. Since a whole lot of what makes organic chemicals react differently is the positioning of the various groups, this is not known to be safe. |
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I hear what the annotations are saying. I am kind of thinking that this could quantify risk to guide which preferred compounds to heptacyclize. |
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Another possibility would be to simply just take every compound that reaches stage 2 or 3 approval then make heptacycle versions to test them once the approved drug becomes popular. Thats sort of a peculiar way to double the reputational length of a drug patent. Prozac works then develop prozac 7, when prozac lapses then the potentially better, yet name recognized Prozac 7 continues on. |
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The emphasis is actually on creating more better new drugs than just giving known drugs more earning power, yet there does appear to be a financial benefit (of sorts) to create the beneficial variants as well. |
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Along with the general benefits the originating thought was, how could I make all the known nootropics more effective. Using a heptacycle to slightly change the angles looks like a way to make all these drugs more effective. I think it would be wonderful to develop highly effective sideeffectless nootropics like the 7 racetams or other drugs that minimize alzheimers |
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My point is that Prozac 7 would not neccesarily be an anti-depressant. It might be one, or a completely different drug, or a deadly toxin. The physical geometry of the molecule has as much to do with how it functions in the body as the chemical makeup. The ring isn't just a place-holder. |
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I do think these molecules would be very different. Setting aside the whole aromatization thing and considering just plain rings: a hop from hexane to pentane, all the things hanging off that ring will be at a differnet orientation. |
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It might be simpler to stick with the same molecules
but make them a different colour. |
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