190076-85-8Relevant articles and documents
Substituted hexahydrobenzo[f]thieno[c]quinolines as dopamine D1- selective agonists: Synthesis and biological evaluation in vitro and in vivo
Michaelides, Michael R.,Hong, Yufeng,DiDomenico Jr., Stanley,Bayburt, Erol K.,Asin, Karen E.,Britton, Donald R.,Lin, Chun Wel,Shiosaki, Kazumi
, p. 1585 - 1599 (2007/10/03)
A series of substituted 9,10- dihydroxyhexahydrobenzo[f]thieno[c]quinolines (TB[f]Q), varying with respect to the position of the thiophene relative to the benzo[f]quinoline core and the nature and position of the substituent on the thiophene, were prepared and evaluated for their affinity and selectivity for the dopamine D1-like receptor. The thieno[3,2-c]B[f]Q regioisomers bearing a small alkyl (C1-C3) substituent at the 2 position were potent (K(i) 50) D1 agonists with close to full agonist activity (IA > 85%). The compounds were resolved and found to exhibit a high level of enantiospecificity in their interaction with the D1 receptor. Selected compounds were tested in vivo in the 6-OHDA rodent model of Parkinson's disease and for their liability to produce seizure-like activities in mice. (5aR)-trans-2-Propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5-azacyclopent-1- ena[c]phenanthrene-9,10-diol (5) emerged as the compound with the best overall in vivo profile in terms of potency (ED50 = 0.04 μmol/kg) and safety.
