86761-34-4Relevant academic research and scientific papers
4-Phenoxybutoxy-substituted heterocycles - A structure-activity relationship study of blockers of the lymphocyte potassium channel Kv1.3
Bodendiek, Silke B.,Mahieux, Cedrick,Haensel, Wolfram,Wulff, Heike
experimental part, p. 1838 - 1852 (2009/09/08)
The voltage-gated potassium channel Kv1.3 constitutes an attractive pharmacological target for the treatment of effector memory T cell-mediated autoimmune diseases such as multiple sclerosis and psoriasis. Using 5-methoxypsoralen (5-MOP, 1), a compound isolated from Ruta graveolens, as a template we previously synthesized 5-(4-phenoxybutoxy)psoralen (PAP-1, 2) which inhibits Kv1.3 with an IC50 of 2 nM. Since PAP-1 is more than 1000-fold more potent than 5-MOP, we here investigated whether attaching a 4-phenoxybutoxy side chain to other heterocyclic systems would also produce potent Kv1.3 blockers. While 4-phenoxybutoxy-substituted quinolines, quinazolines and phenanthrenes were inactive, 4-phenoxybutoxy-substituted quinolinones, furoquinolines, coumarins or furochromones inhibited Kv1.3 with IC50s of 150 nM to 10 μM in whole-cell patch-clamp experiments. Our most potent new compound is 4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromene-7-thione (73, IC50 17 nM), in which the carbonyl oxygen of PAP-1 is replaced by sulfur. Taken together, our results demonstrate that the psoralen system is a crucial part of the pharmacophore of phenoxyalkoxypsoralen-type Kv1.3 blockers.
An efficient large scale synthesis of coumarins by a dealkylative boron- mediated ring closure of 3-(ortho-methoxyaryl)propenoic esters
Dubuffet,Loutz,Lavielle
, p. 929 - 936 (2007/10/03)
Various substituted coumarins 3 were prepared via a dealkylative boron- mediated ring closure of ortho-methoxycinnamates 2.
