1033221-32-7Relevant 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
, 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.
