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delorazepam potentiation.

/navarone/

/navarone/

Bluelighter
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I was recently poderig on the possible modificacionof a very rare benzodiazepine: delorazepam

delorazepam known as En in italy:
Delorazepam.png


those 2 chlorine atomes look very suscectible.
i fhteresanybody here who deepley knows somehing abot chemestry.

wha kind of reaction would u consider.

in my opininion addin 2 benzenerings to the aryl chlorides would meke the molecule more a-polar

or mabe just turn those chlorines n sme other grouns.

i leave the thinlking to you.
from my point of view the modification of the benzo could give fasinating results.

how about ading 2 stearic acid chains? i guess that would make it more soluble intthe brain-fat structure.

i dont know.......im jus asking for opinions.
we are not talking about makng drugs hre but.....changng em a lil=D ....thats not againsts the rules isn't it?
 
What are you talking about? Do you have any reason for these suggestions? Why don't you look at a paper that looks at the structural activity relationships?

First, those chlorine atoms aren't "susceptible"- they aren't stripped to leave free chlorine ions floating around your body.

Yeah, you could make an analogue with something in place of the chloro's. Like what? Alkyl groups? You've now got an inactive molecule. There's a reason you find halogens on virtually every benzo. They're neccessary for activity. One of them is, that is.

Remove the other and replace it with something else and you now have a molecule that's 10-100x less potent.

Why on earth would you want to attach stearic acid moleules to this drug? There are MUCH better ways of making a more water or fat soluble drug. Why not a simple methyl ester?

i leave the thinlking to you.
from my point of view the modification of the benzo could give fasinating results.
Click to expand...

That's a good thing, because none of your suggestions make sense. You want to attach a phenyl group on the chlorines? That'll result in a Cl+, and I don't think you can replace a carbon with a chlorine in benzene ring. Sigma can't find it in anything.

Instead of starting a dozen new threads for things you haven't reasoned out, how about thinking one through first and having reasons for your suggestions (there's no way you would suggest getting rid of the halogens if you'd made even a cursory glance over the past threads here about benzos or even just weakly cruised through the benzos in wikipedia and looked at what resulted in more potent benzos or benzos that were more widely abused).
 
Thanks for ur friendly response,
i aprecaiate the way u made me look like a copmlete idiot.

ok then wut suggestions do you offeron the matter?

switching those chlorines with fluorines...i dont knnow...im no big chemist i was just wondering. from my pont of view theres many things that could be attached or substituted on those chlorines.
if u think the molecule is perfect beno then....cheers.

i wish u a good day my friend.
 
Thanks for ur friendly response,
i aprecaiate the way u made me look like a copmlete idiot.
Click to expand...

You've managed that all on your own, not even counting spelling.

Your suggestions were completely illogical. I definitely don't think that it's the perfect benzo, but your suggestions only make it inactive or worse.

It's not hard to find a decent overview of the benzo SAR on this website or somewhere else online. You would then look at what that SAR says would make for a better benzo; Then, based upon what you're looking for- more hypnotic, more anxiolytic, you might suggest modifications based upon what the SAR says would produce your 'ideal benzo.'

1. You don't want to change much about the halogens. Sub with a nitro or a flouro, nothing else (and even then you start losing potency rapidly, but you get a lot more sedation if that's what you were looking for).

2. You can't really just attach things to a chlorine atom. I'm not aware of any use of a secondary halogen.

3. You'd be a lot further ahead modifying *other* positions.
 
the reason why make i make som many ypo is because im on 50mg ambien and using annoting rubber keyboard.

anyway, so your saiyng that no to modifying its strucsture is poiintless?
let meunderstand ur negligence towards the possible structural modifictionof this 'reactive' benzo.

the basic question is...in therre any way o chemically potentiate this benzo?
if u think m question is stupid that dont even bother sayin it.
 
anyway, so your saiyng that no to modifying its strucsture is poiintless?
let meunderstand ur negligence towards the possible structural modifictionof this 'reactive' benzo.
Click to expand...

Did I say that modifying it is pointless? No, not once. I did say that the modifications you suggested are illogical and senseless, and I gave you good ideas for ways you could take a little time to find what modifications would be smart.

What do you mean by "chemically potentiate it"- that language doesn't mean anything in the context of what you're talking about. I'm assuming you mean either

a. synthetically alter it (using it as a precursor)

or

b. take something else to make it stronger.
 
Be nice Hammilton. Although I agree the answer to this question would have been better sought by looking at some benzo SAR studies, there are enough of them available online!

You want to potentiate this molecule, then try replacing the 7-chloro with trifluoromethyl, the 2'-chloro with fluorine, and add a methyl to the N1 nitrogen.
 
You mean what I'd do to make it more potent?

I'd start with a different molecule. I don't think it pays to try altering this.

I'd be interested in replacing the carbonyl with a furan ring (with the oxygen properly situated, of course).


^ ms- is the trifluoromethyl group used in like that ever? I don't think I've ever seen it (substructure search at Sigma can't find a benzo with a trifluoromethyl group at 7 or 2' position.
 
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I guess i Grinard reagent would be optimal to add something to this molecule according toth thory:

R'-Cl + Cl-Mg-R" ---> R'-R" + MgCl2

or:

R'-Cl + R"-(C=O)-R"' --[H20/H+]--> R"-(R'-C-R"')-OH

Or we could judt bssify the molecule withs strongbsdr to turn Cls in OHs and then reac em morea easiily?

BTW wut would happed in a benzodiazepine would be highly oxidised (lest say 100% H2SO4 or umthing else

Something tells me that NO2 group would make some major difference
 
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they don't need 'a lot' of halogens, they a (pseudo)halogen on the 7 carbon to be active, and a halogen at the 2' carbon only makes it more potent.

Sometimes replacing a halogen with a pseudohalogen makes good sense- if you want a more sedating (and euphoric IMHO) you'd want a nitro group on the 7-carbon, and then to make up for reduced potency, a halogen on the 2' carbon.

I'm assuming this exists, but is there a traizolo-nitro-benzo?
 
Ham-milton said:
I'm assuming this exists, but is there a triazolo-nitro-benzo?
Click to expand...

http://en.wikipedia.org/wiki/Loprazolam

Also yeah I'm not sure whether a nitro or a trifluoromethyl would be the better substituent, the only TFM-substituted benzo I've seen is that clobazam analogue MattPsy pointed out, but in that case at least it makes the drug significantly more potent and longer acting, and TFM should at least avoid the possible toxicity that the nitro benzos have been linked with. Also note that there doesn't necessarily have to be a halogen on the 7-position, ethyl or ethynyl works just as well (i.e. etizolam, QH-ii-066)
 
I don't wanna be mean but could you PLZ check spelling sometimes? My english is far away from being perfect but this above is AWFUL.

Btw, synthesis discussion is (unfortunately) against the forum rules. Just this: Grignard-chemistry is not considered to be first choice here. First, with 2 chlorine present the reaction wouldn't be selective. Second, the resulting products are, as Hammilton elaborated already nicely, not active.

Murph
 
Yeah, clonazepam is the nitro version of this drug. And clonazepam seems to be a better drug.

btw- was it you that wrote the delorazepam entry? good god.

What exactly is the point of this thread?
 
/navarone/ said:
my question is if it was possible to potentiate delorazepam by adding 'sumthing' to those chlorines.
Click to expand...
As long as nobody posts a synthetic route with details, this shouldn't be against the rules...

IMO there's no way to 'potentiate' deslorazepam in the proposed manner. All (chemically possible) modifications will lead to compounds with decreased potency.
If you want a benzo with even higher potency than deslorazepam, you would have to synthesize it from scratch... Deslorazepam has already a very high potency. Increasing it equals seriously risking your health/life.
 
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