27673-48-9Relevant academic research and scientific papers
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.
Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity
Bajaj, Priyanka,Sreenilayam, Gopeekrishnan,Tyagi, Vikas,Fasan, Rudi
supporting information, p. 16110 - 16114 (2016/12/26)
Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.
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.
Reduction of polycyclic aromatic hydrocarbons promoted by cobalt or manganese nanoparticles
Nador, Fabiana,Moglie, Yanina,Vitale, Cristian,Yus, Miguel,Alonso, Francisco,Radivoy, Gabriel
experimental part, p. 4318 - 4325 (2010/07/09)
A new methodology for the partial reduction of polycyclic aromatic and heteroaromatic hydrocarbons under mild reaction conditions is presented, the process being a reasonable alternative to the catalytic hydrogenation or the Birch reaction. The reduction protocol described is based on the use of cobalt or manganese nanoparticles generated in situ in a simple and economic way, by reduction of commercially available CoCl2·6H2O or MnCl2·2H2O in the presence of lithium sand and the corresponding PAH, acting itself as an electron carrier. The use of a deuterium-oxide-containing cobalt(II) salt allows the simple preparation of deuterium labeled products. The regiochemistry and degree of reduction in the case of 1-substituted naphthalene derivatives markedly depends on the nature of the metal-NPs used.
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.
Photo-Fries and Fries reaction of 5,8-dihydro-1-naphthyl esters
Sriraghavan, Kamaraj,Ramakrishnan, Vayalakkavoor T.
, p. 1791 - 1796 (2007/10/03)
Systematic studies were performed on the photo-Fries and the Fries reaction of aliphatic, aliphatic unsaturated, aromatic and aromatic unsaturated esters of 5,8-dihydro-1-naphthol. The Fries reaction of 5,8-dihydro-1-naphthyl acetate in various solvents is also reported.
A facile synthesis of N-aryl aziridines
Sriraghavan,Ramakrishnan
, p. 1105 - 1121 (2007/10/03)
Reaction of N-aryl-β-amino alcohols with p-toluenesulphonyl chloride under phase transfer catalytic condition gave the corresponding N-aryl aziridines in good yields, whereas N-alkyl-β-amino alcohol [for e.g., L-ephedrine] gave the corresponding N-tosyl derivative as the major product, along with the expected N-alkyl aziridines in lower yield.
NOVEL AND FACILE REDUCTION OF PHENOL DERIVATIVES WITH SAMARIUM DIIODIDE-BASE SYSTEM
Kamochi, Yasuko,Kudo, Tadahiro
, p. 4169 - 4172 (2007/10/02)
Phenol was rapidly reduced with samarium diiodide-base system in the presence of protic solvent at room temperature to afford 3-cyclohexen-1-ol accompanied by cyclohexanol.The similar reduction of 4-methoxyphenol and 2-naphthol gave 4-hydroxycyclohexanone and 1,2,3,4-tetrahydro-2-naphthol in excellent yield, respectively.
ELECTROCHEMICAL REDUCTIONS IN LIQUID AMMONIA: ELECTROLYTIC BIRCH REACTIONS AND CHEMICAL BOND FISSIONS
Chaussard, J.,Combellas, C.,Thiebault, A.
, p. 1173 - 1174 (2007/10/02)
A procedure of electrochemical reduction in liquid ammonia using a single-compartment cell equiped with a soluble anode is described and illustrated in the case of aromatic compounds and esters.
Propionamidoxime derivatives
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, (2008/06/13)
Propionamidoxime derivatives which are compounds of formula (I) STR1 in which A is a tetrahydronaphthyl or dihydronaphthyl radical and their pharmaceutically acceptable salts are valuable for treatment of the central nervous system and depression. The above compounds are prepared by reacting the nitrile (II) STR2 with hydroxylamine hydrochloride.
