Fertile
Bluelighter
- Joined
- Mar 31, 2022
- Messages
- 1,627
Lefetamine (SPA/Sanetol) is an opioid around twice the potency of dihydrocodeine and a stimulant (DRI). Looking at the active conformation, it appears that the 2 aromatic rings overlay the A & C rings of morphine. Borrowing from other phenanthracene opioids, placing a methyl group in the same position as the 6-hydroxyl of morphine is known to increase the potency of such compounds.
With that in mind I've drawn lefetamine in it's active conformation, methyldesorphine so show the 6-methyl and a possible lefetamine derivative that should be both legal and some 50% more potent as an opioid.
Now I have not included the meta phenol moiety of AD-1211 & diphenylpipernol as the QSAR of these compounds it not entirely clear. It MAY be the case that the addition of a phenol will lower the LogP resulting in lefetamine analogues being less potent while derivatives with large alkyl groups will be less affected resulting in their potency being affected much less.
So while this would be interesting, I feel that the addition of a single methyl is the best way to proceed since it's only a small modification. LogP will be increased, but it remains to be seen just how much.
The advantages of this class is that they are synthetically and chemically simple. It IS chiral which generally invokes increased activity and the fact that it possesses stimulant activity MAY be of value so some people. But any other examples of this 1,2-diphenylethylamine class would be value in elucidating the QSAR so if anyone has further examples, they would be gratefully received.
BTW it's also a surprise that it is the meta phenol that increases activity. IF it overlays morphine, one would expect the para phenol to be appropriate. I will conclude by adding that if the compound is consumed via a parenteral route, the acetyl ester of the phenol is very likely to double the potency of the given compound. That would result in a product with a potency around ½ the potency of morphine. Not amazing, but certainly of utility, especially for those seeking to detoxify from more mainstream, more potent opioids.
With that in mind I've drawn lefetamine in it's active conformation, methyldesorphine so show the 6-methyl and a possible lefetamine derivative that should be both legal and some 50% more potent as an opioid.
Now I have not included the meta phenol moiety of AD-1211 & diphenylpipernol as the QSAR of these compounds it not entirely clear. It MAY be the case that the addition of a phenol will lower the LogP resulting in lefetamine analogues being less potent while derivatives with large alkyl groups will be less affected resulting in their potency being affected much less.
So while this would be interesting, I feel that the addition of a single methyl is the best way to proceed since it's only a small modification. LogP will be increased, but it remains to be seen just how much.
The advantages of this class is that they are synthetically and chemically simple. It IS chiral which generally invokes increased activity and the fact that it possesses stimulant activity MAY be of value so some people. But any other examples of this 1,2-diphenylethylamine class would be value in elucidating the QSAR so if anyone has further examples, they would be gratefully received.
BTW it's also a surprise that it is the meta phenol that increases activity. IF it overlays morphine, one would expect the para phenol to be appropriate. I will conclude by adding that if the compound is consumed via a parenteral route, the acetyl ester of the phenol is very likely to double the potency of the given compound. That would result in a product with a potency around ½ the potency of morphine. Not amazing, but certainly of utility, especially for those seeking to detoxify from more mainstream, more potent opioids.
(and wondering how it's xmas without 'The Great Escape', 'Mary Poppins' etc on the telly!)