2-halo methyl Qualones?

[Ham-milton]

Does anyone know if other 2-halo methyl analogues of known methaqualone-type drugs have been synthesized besides afloqualone (which wasn't exactly a winner)?

Diproqualone, not a 2-halomethyl, but the only other qualone I've seen that has much derivation in structure. There's 4/6th of a ring missing on this one.

Does anyone think that anything *but* the central ring with the double bonded oxygen is neccessary for activity a qualone's activity? I mean, if you were to strip away all the other rings, but left the cyclohexene w/the dbl oxygen (correct term?) would you still have an active depressant?

 

[hussness]

Are you referring to analogs that were purportedly online around '98?
The reference is here, but I can't read German:
Zwölfte Verordnung zur Änderung betäubungsmittel rechtlicher Vorschriften. Bundesgesetzblatt 1998: Part I Number 68, p. 3126. 7 October 1998.

It seems as though diproqualone is the only drug of the class still being prescribed.
I dug up a number of journal articles from the Indian Journal of Medicinal Chemistry concerning the synthesis of qualones. Apparently, methaqualone was discovered by some Indian researcher in the 50's who was looking for anti-malaria drugs. I haven't been able to track down the original article.
I have often wondered if methaqualone's pharmacological effects are pretty much those of a barbiturate. Is anyone aware of data on whether or not they bind to the same site on the GABA receptor?
I've heard that a regular dose range for methaqualone is around 300 mg. Is this rather large dosage due to a large volume of distribution, or low affinity, or what? Has anyone ever made a methaqualone like drug that is active at much smaller doses?
I would be very interested in a SAR or at least some pharmacological data for this drug.

 

[jasoncrest]

Diproqualone and Chloroqualone were prescribed years ago in France, with maybe a few other -qualones, I don't remember which though (Mecloqualone I think).

 

[hussness]

According to Beckman Coulter, which manufactures a reagent for methaqualone drug tests, the drug is extensively metabolized, with the major metabolites being the N-oxide, and conjugated 2', 3', 4', and 2 hydroxyl derivatives. Only 0.2% is excreted unchanged. I haven't found information yet on which, if any, of these metabolites are active. If this information is true, I would guess that methaqualone is primarily a prodrug.

 

[Ham-milton]

The only 2-halo methyl qualone, that I know of is Afloqualone.

 

[UnfortunateSquid]

There are more than a few on wiki, search for afloqualone.

 

[haribo1]

The only report I have read on mecloqualone said it wasn't anywhere near as nice as methaqualone. If you track down a snapshot of Rhodium's site, you will find an article on all the analogs found in S.Africa (Lude HQ) and non of them was a halo analog.

 

[jasoncrest]

The only report I have read on mecloqualone said it wasn't anywhere near as nice as methaqualone.

Yeah Mecloqualone seems to be a good hypnotic, but nothing else. It lacks the antihistamine, muscle-relaxant, anesthesic and anxiolytic properties of Methaqualone.....

Chloroqualone seems to be shitty: it's an antitussive (Methaqualone has this property too), with sedative side-effects.

I was surprised about something though: I got these informations from a very reliable french website, and they also indicate the addiction potential of each drug.
Both Methaqualone and Mecloqualone are classified as "addictive" (like Barbituates, "strongly addictive" is for Methamphetamine and Fentanyls.....); while Diproqualone and Cloroqualone are classified as "non addictive"......