AlsoTapered
Bluelighter
- Joined
- Apr 1, 2023
- Messages
- 3,076
There are 20 patents that examine the QSAR of tianeptine after it's opiate activity was discovered. The most interesting is:
US20190047970A1 'Carboxylic diarylthiazepineamines as mu-opioid receptor agonists'
Which discloses a closely related compound that demonstrates MOR affinity over x160 higher (at the MOR) but (negligible) DOR activity. Now, the study doesn't demonstrate if the ligand is a superagonist (like tianeptine) or indeed agonist, partial agonist, silent agonist, inverse agonist or antagonist.
What it DOES underline is the size of the 3 substituent. I am reminded of ciramadol. Reaxys indicated that an analogue of ciramadol in with the meta -OH was replaced by a para -Cl was a known compound but I could find no reference even after searching for a long time.
It's still rather unexpected that the secondary amine is the most potent N-substitution but the patent doesn't comprehensively check every homologue. It seems likely to me that it's the two aromatics, para halide and (I suspect) the lone-pairs of the O that provides four of the eight recognized key moieties that possess MOR affinity.
It should be noted that to the best of my knowledge, the scaffold let alone compound 7b are controlled anywhere on earth and any business who produces tianeptine could readily switch to producing 7b.
But please don't assume that just because the affinity of 7b is some x160 higher, it will automatically prove to be x160 more potent.
It's interesting to explore the QSAR of a new class of opioid but we have absolutely NO safety information. If, like tianeptine, 7b proves to be a superagonist, it could prove to be an extremely hazardous compound. BEWARE.
US20190047970A1 'Carboxylic diarylthiazepineamines as mu-opioid receptor agonists'
Which discloses a closely related compound that demonstrates MOR affinity over x160 higher (at the MOR) but (negligible) DOR activity. Now, the study doesn't demonstrate if the ligand is a superagonist (like tianeptine) or indeed agonist, partial agonist, silent agonist, inverse agonist or antagonist.
What it DOES underline is the size of the 3 substituent. I am reminded of ciramadol. Reaxys indicated that an analogue of ciramadol in with the meta -OH was replaced by a para -Cl was a known compound but I could find no reference even after searching for a long time.
Tianeptine homologue - Image on Pasteboard
Tianeptine accidentally provided a novel scaffold for a new class of opioid (although it shares features with ciramadol).
pasteboard.co
It's still rather unexpected that the secondary amine is the most potent N-substitution but the patent doesn't comprehensively check every homologue. It seems likely to me that it's the two aromatics, para halide and (I suspect) the lone-pairs of the O that provides four of the eight recognized key moieties that possess MOR affinity.
It should be noted that to the best of my knowledge, the scaffold let alone compound 7b are controlled anywhere on earth and any business who produces tianeptine could readily switch to producing 7b.
But please don't assume that just because the affinity of 7b is some x160 higher, it will automatically prove to be x160 more potent.
It's interesting to explore the QSAR of a new class of opioid but we have absolutely NO safety information. If, like tianeptine, 7b proves to be a superagonist, it could prove to be an extremely hazardous compound. BEWARE.
