Allosteric modulators of 5-hydroxytryptamine 2C receptor (5-HT2CR)
The disclosure is directed to compounds identified as allosteric modulators of 5-HT 2CR, as well as pharmaceutical compositions and methods using the same. Certain embodiments also include methods of identifying and methods of synthesizing the compounds. Optimization and development of allosteric 5-HT 2CR modulators that bind sites other than the primary ligand binding site generate novel, highly selective, and potent ligands of 5-HT2CR. Such molecules can be used as small molecule probes for the nervous system and as effective therapeutics for a variety of diseases.
1. A compound having the general formula of Formula I
wherein, Y is —NH;
Z is a linear or branched C 1 , C 2 , C 3 , or C 4 , alkyl;
R 1 is hydroxy, or hydroxy substituted C 1-4 alkyl;
R 2 is hydrogen, hydroxy, or hydroxy substituted C 1-4 alkyl;
X is a linear, saturated C 10-15 alkyl; and
R 3 is hydrogen, methyl, or ethyl.
2. The compound of claim 1 , wherein R 1 is a hydroxy substituted C 1 alkyl.
3. The compound of claim 1 , wherein R 2 is hydroxy.
4. The compound of claim 1 , wherein the compound is
(2,4-cis-4-undecyl-piperidine-2-carboxylic acid (2,3-dihydroxypropyl)amide); or
(2,4-cis-4-undecyl-piperidine-2-carboxylic acid (2-hydroxy-1-hydroxymethyl-ethyl)amide).