181642-34-2Relevant academic research and scientific papers
Nonpeptide small molecule agonist and antagonist original leads for neuropeptide FF1 and FF2 receptors
Journigan, V. Blair,Mésangeau, Christophe,Vyas, Neha,Eans, Shainnel O.,Cutler, Stephen J.,McLaughlin, Jay P.,Mollereau, Catherine,McCurdy, Christopher R.
, p. 8903 - 8927 (2015/03/14)
Neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R), and their endogenous ligand NPFF, are one of only several systems responsible for mediating opioid-induced hyperalgesia, tolerance, and dependence. Currently, no small molecules displaying good affinity or selectivity for either subtype have been reported, to decipher the role of NPFF2-R as it relates to opioid-mediated analgesia, for further exploration of NPFF1-R, or for medication development for either subtype. We report the first nonpeptide small molecule scaffold for NPFF1,2-R, the guanidino-piperidines, and SAR studies resulting in the discovery of a NPFF1 agonist (7b, Ki = 487 ± 117 nM), a NPFF1 antagonist (46, Ki = 81 ± 17 nM), and a NPFF2 partial antagonist (53a, Ki = 30 ± 5 nM), which serve as leads for the development of pharmacological probes and potential therapeutic agents. Testing of 46 alone was without effect in the mouse 48 °C warm-water tail-withdrawal test, but pretreatment with 46 prevented NPFF-induced hyperalgesia.
