27673-48-9Relevant articles and documents
Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the vesicular acetylcholine transporter
Roslin, Sara,De Rosa, Maria,Deuther-Conrad, Winnie,Eriksson, Jonas,Odell, Luke R.,Antoni, Gunnar,Brust, Peter,Larhed, Mats
, p. 5095 - 5106 (2017)
Herein, new ligands for the vesicular acetylcholine transporter (VAChT), based on a benzovesamicol scaffold, are presented. VAChT is acknowledged as a marker for cholinergic neurons and a positron emission tomography tracer for VAChT could serve as a tool for quantitative analysis of cholinergic neuronal density. With an easily accessible triflate precursor, aminocarbonylations were utilized to evaluate the chemical space around the C5 position on the tetrahydronaphthol ring. Synthesized ligands were evaluated for their affinity and selectivity for VAChT. Small, preferably aromatic, N-substituents proved to be more potent than larger substituents. Of the fifteen compounds synthesized, benzyl derivatives (±)-7i and (±)-7l had the highest affinities for VAChT. Compound (±)-7i was chosen to investigate the importance of stereochemistry for binding to VAChT and selectivity toward the σ1 and σ2 receptors. Enantiomeric resolution gave (+)-7i and (?)-7i, and the eutomer showed seven times better affinity. Although racemate (±)-7i was initially promising, the affinity of (?)-7i for VAChT was not better than 56.7 nM which precludes further preclinical evaluation. However, the nanomolar binding together with the ready synthesis of [11C]-(±)-7i shows that (?)-7i can serve as a scaffold for future optimizations to provide improved 11C-labelled VAChT PET tracers.
Synthesis and SAR study of a novel series of dopamine receptor agonists
Risgaard, Rune,Jensen, Martin,J?rgensen, Morten,Bang-Andersen, Benny,Christoffersen, Claus T.,Jensen, Klaus G.,Kristensen, Jesper L.,Püschl, Ask
, p. 381 - 392 (2014/01/17)
The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D1 and D2 receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl- 3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D1 and D2 receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine.
Synthesis of dihydrobenzo[h]coumarins and their 4-methyl analogs
Wang, Yang,Huang, Shaoxu,Xia, Peng
, p. 3141 - 3156 (2007/10/03)
Dihydrobenzo[h]coumarins (5a-7a) and their 4-methyl analogs (5b-7b) were synthesized from 1-naphthol via two different synthetic routes. One pathway is the direct condensation of 5,8-dihydro-1-naphthol (9) with malic acid or ethyl acetoacetate, affording 7,10-dihydrobenzo[h]coumarins 7a and 7b, respectively. The other is through the oxidation of 7,8,9,10-tetrahydrobenzo[h] coumarins (15a-b), followed by the reduction of the carbonyl group and dehydration of hydroxyl group, giving 7,8-dihydrobenzo[h]coumarins (5a, b) and 9,10-dihydrobenzo[h]coumarins (6a, b). The regio selectivities for the oxidation reactions of 15a, b were rationalized on the basis of quantum chemical calculations and further confirmed by the X-ray crystallographic analysis of the derivatives of oxidation products. Copyright Taylor & Francis, Inc.
