Synthesis of J-113397, the first potent and selective ORL1 antagonist

The first potent and selective small molecule ORL1 antagonist 1-[(3R,4R)-1- cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-1-3-dihydro-2H-benzimidazol-2 -one (J- 113397)was synthesized. J-113397 is the only available potent and selective ORL1 antagonist, which is a very useful pharmacological tool for elucidating the physiological roles of the nociceptin-ORL1 system. J-113397 was synthesized from ethyl 4-oxo-3-piperidinecarboxylate and a coupling re action of 2-fluorobenzene with 4-amino-ethoxycarbonylpiperidine is a key st ep. (C) 2001 Elsevier Science Ltd. All rights reserved.