1033226-28-6Relevant articles and documents
Discovery of novel selective norepinephrine inhibitors: 1-(2-morpholin-2-ylethyl)-3-aryl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxides (WYE-114152)
O'Neill, David J.,Adedoyin, Adedayo,Bray, Jenifer A.,Deecher, Darlene C.,Fensome, Andrew,Goldberg, Joel A.,Harrison, Jim,Leventhal, Liza,Mann, Charles,Mark, Lilly,Nogle, Lisa,Sullivan, Nicole R.,Spangler, Taylor B.,Terefenko, Eugene A.,Trybulski, Eugene J.,Uveges, Albert J.,Vu, An,Whiteside, Garth T.,Zhang, Puwen
experimental part, p. 6824 - 6831 (2011/12/04)
Sequential modification of the previously identified 4-[3-aryl-2,2-dioxido- 2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols led to the identification of a new series of 1-(2-morpholin-2-ylethyl)-3-aryl-1,3-dihydro- 2,1,3-benzothiadiazole 2,2-dioxides that are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound 10b (WYE-114152) had low nanomolar hNET potency (IC50 = 15 nM) and good selectivity for hNET over hSERT (>430-fold) and hDAT (>548-fold). 10b was additionally bioavailable following oral dosing and demonstrated efficacy in rat models of acute, inflammatory, and neuropathic pain.
