Limpet_Chicken
Bluelighter
Has anyone ever tried those BAY series cannabinoids. The ones with that funky triflurobutanesulfonyl sidechain?
BAY-38-7271 is a pretty potent looking full agonist at both CB1 and CB2, Ki values of 2.91nM at CB1 and 4.24nM at CB2, and is currently in some phase II clinical trials, based off a hydroxylated methylindane core, with a triflurobutanesulfonylphenyl group, linked together as the phenyl ether. This one has always piqued my curiosity as one Id love to try, and there is another one in the BAY series, this one a partial agonist. Ki values of 48.3nM at CB1 and 45.5nM at CB2. Similar structure with the 4,4,4-triflurobutanesulfonyl sidechain, this time the ether linked group is a phenyl ring bearing both a nitrile functionality and a trifluromethyl group. The nitrile group makes me somewhat cautious about it being smoked, but its known to be orally active..
The basic pharmacophore in these seems to be the 4,4,4-triflurobutanesulfonyl moiety attached by an ether link to the 3-position of a substituted phenyl grup, or the benzene ring of a heterocyclic/bicyclic ring. I bet there is room here using the 4,4,4-triflurobutanesulfonylphenyl moiety for structural playing about with the ether link to the 3-position of that phenyl/indane ring, to produce an army of new CB1/CB2 agonists.
Here are the structures of the two compounds in question:
3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl 4,4,4-trifluoro-1-butanesulfonic acid ester is BAY 59-3074, the partial agonist
BAY-38-7271, the full agonist is (-)-(R)-3-(2-Hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluorobutyl-1-sulfonate. I wonder if the S isomer is also active. Anybody know?
Both are on wikipedia if anyone cares to look.
Anybody tries either of these? They are both active in vivo, and the full agonist is reportedly around as potent as CP-55-940. I liked CP-55-940 quite a lot when I tried it, possibly my favourite cannabinoid to date. I've never seen any reports of human bioassays though, they seem fairly obscure, and I just bet there is room for further chemical development by playing around with different heterocycles where that 3-positioned phenyl ether linker is. Benzofuran, benzothiophenes, substituted indoles, maybe things like piperidine, piperazine (unless aromaticity of the ring is needed for activity), perhaps pyridine ring, the list of tweaks is potentially endless, and it would help to establish a full SAR of these compounds. I assume the 4,4,4-triflurobutanesulfonic ester is binding in the same place at CB1 that the alkyl tail of things like THC and HU-210, or the substituted alkyl sidechain on the indolic nitrogen of some of those AM series compounds or the substitution on the indolic nitrogen in JWH-018 and friends?
BAY-38-7271 is a pretty potent looking full agonist at both CB1 and CB2, Ki values of 2.91nM at CB1 and 4.24nM at CB2, and is currently in some phase II clinical trials, based off a hydroxylated methylindane core, with a triflurobutanesulfonylphenyl group, linked together as the phenyl ether. This one has always piqued my curiosity as one Id love to try, and there is another one in the BAY series, this one a partial agonist. Ki values of 48.3nM at CB1 and 45.5nM at CB2. Similar structure with the 4,4,4-triflurobutanesulfonyl sidechain, this time the ether linked group is a phenyl ring bearing both a nitrile functionality and a trifluromethyl group. The nitrile group makes me somewhat cautious about it being smoked, but its known to be orally active..
The basic pharmacophore in these seems to be the 4,4,4-triflurobutanesulfonyl moiety attached by an ether link to the 3-position of a substituted phenyl grup, or the benzene ring of a heterocyclic/bicyclic ring. I bet there is room here using the 4,4,4-triflurobutanesulfonylphenyl moiety for structural playing about with the ether link to the 3-position of that phenyl/indane ring, to produce an army of new CB1/CB2 agonists.
Here are the structures of the two compounds in question:
3-[2-Cyano-3-(trifluoromethyl)phenoxy]phenyl 4,4,4-trifluoro-1-butanesulfonic acid ester is BAY 59-3074, the partial agonist
BAY-38-7271, the full agonist is (-)-(R)-3-(2-Hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluorobutyl-1-sulfonate. I wonder if the S isomer is also active. Anybody know?
Both are on wikipedia if anyone cares to look.
Anybody tries either of these? They are both active in vivo, and the full agonist is reportedly around as potent as CP-55-940. I liked CP-55-940 quite a lot when I tried it, possibly my favourite cannabinoid to date. I've never seen any reports of human bioassays though, they seem fairly obscure, and I just bet there is room for further chemical development by playing around with different heterocycles where that 3-positioned phenyl ether linker is. Benzofuran, benzothiophenes, substituted indoles, maybe things like piperidine, piperazine (unless aromaticity of the ring is needed for activity), perhaps pyridine ring, the list of tweaks is potentially endless, and it would help to establish a full SAR of these compounds. I assume the 4,4,4-triflurobutanesulfonic ester is binding in the same place at CB1 that the alkyl tail of things like THC and HU-210, or the substituted alkyl sidechain on the indolic nitrogen of some of those AM series compounds or the substitution on the indolic nitrogen in JWH-018 and friends?
