- Substituted hexahydrobenzo[f]thieno[c]quinolines as dopamine D1- selective agonists: Synthesis and biological evaluation in vitro and in vivo
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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.
- Michaelides, Michael R.,Hong, Yufeng,DiDomenico Jr., Stanley,Bayburt, Erol K.,Asin, Karen E.,Britton, Donald R.,Lin, Chun Wel,Shiosaki, Kazumi
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p. 1585 - 1599
(2007/10/03)
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- TETRACYCLIC COMPOUNDS AS DOPAMINE AGONISTS
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A tetracyclic compound of the formula: STR1 wherein A and the atoms to which it is attached and the optional double bond represent a mono-or di-heterocyclic ring selected from: STR2 wherein R 1, R. sup.2, R 3, R 4 and X are specifically defined, which compounds are useful in the treatment of dopamine-related neurological, psychological and cardiovascular disorders as well as in the treatment of substance abuse and other addictive behavior disorders, cognitive impairment and attention deficit disorder.
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- Side-chain Effects on the Fragmentation Behaviour of Alkylthiophenes
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The processes leading to the fragment ions formed from alkylthiophene molecule ions by benzylic cleavage without and with transfer of one hydrogen from the side-chain to the ring and the influence of additional methyl groups on the relative importance of these two fragmentation reactions were investigated.
- Lange, D.,Budzikiewicz, H.
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p. 432 - 438
(2007/10/02)
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