| 18448337 |
Okamoto O, Kobayashi K, Kawamoto H, Ito S, Yoshizumi T, Yamamoto I, Hashimoto M, Shimizu A, Takahashi H, Ishii Y, Ozaki S, Ohta H: Novel ORL1-selective antagonists with oral bioavailability and brain penetrability. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3282-5. Epub 2008 Apr 28.
Following the discovery of 5-chloro-6-[piperazin-1-yl]-1H-benzimidazole as a novel pharmacophore for potent and selective ORL1 antagonist activity, optimization of this new lead by introduction of a methyl substitution on the piperazine ring resulted in a highly potent and selective, orally available, and brain penetrable ORL1 antagonist, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1 -yl]-1H-benzimidazole. Stereochemistry of the methyl substituent on the piperazine ring to control the functional activity of other opioid receptors is also described. |
32(0,1,1,2) |