84049-33-2Relevant academic research and scientific papers
COMPOUNDS AND COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO NTRK
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, (2017/03/14)
This invention relates to inhibitors of NTRK that are active against wild-type NTRK and its resistant mutants.
Synthesis of novel 4- and 5-substituted benzyl ether derivatives of vesamicol and in vitro evaluation of their binding properties to the vesicular acetylcholine transporter site
Scheunemann, Matthias,Sorger, Dietlind,Wenzel, Barbara,Heinitz, Katrin,Schliebs, Reinhard,Klingner, Margrit,Sabri, Osama,Steinbach, Joerg
, p. 1459 - 1465 (2007/10/03)
Detection of the central cholinergic deficits, a consistent feature of Alzheimer's disease, is essential to allow preventive measures and/or symptomatic treatment already at a very early stage of the disease. The vesicular acetylcholine transporter (VAChT) represents an appropriate target to establish PET radiotracer that are adequate for brain imaging the loss of cholinergic terminals. Here we describe the synthesis and binding characteristics of novel derivatives of vesamicol, known to represent a specific antagonist of VAChT sites. Novel benzyl ether derivatives of vesamicol either 4- or 5-substituted at the cyclohexylring have been synthesized by different regioselective ring opening reactions of a same epoxide precursor. The affinity and selectivity of the novel compounds to VAChT sites were analyzed by competitive radioligand binding studies in rat brain and liver membrane preparations using tritium labeled radioligands. The 4-substituted fluorobenzylether of vesamicol 10b was shown to exhibit a high affinity to VAChT sites (Ki-value10b=10.7±1.7 nM), but demonstrated also binding capacities to sigma receptors (Ki-value10b=18.5±6.9 nM, [3H]DTG; K i-value10b=30.6±9.6 nM, [3H]haloperidol) . The data suggest the potential of vesamicol derivatives to design appropriate radiotracer for PET imaging of central cholinergic deficits.
Synthesis and inhibitory properties of (1R,2R,4R,6R)-6-O-(2-hydroxyethyl)cyclohexane-1,2,4,6-tetraol derivatives: Mechanistic probes for the inositol monophosphatase reaction
Schulz, Juergen,Gani, David
, p. 657 - 670 (2007/10/03)
The phosphate derivatives 2, 3 and 4 of 6-O-(2-hydroxyethyl)cyclohexane-1,2,4,6-tetraol have been designed to inhibit inositol monophosphatase, the putative target for lithium therapy, by interacting simultaneously with both cofactor metal ions at the active site of the enzyme. The compounds have been synthesised, via the known key common intermediate cyclohexene oxide, from cyclohexane-1,4-diol in moderate yield, and have been tested for activity in standard enzyme assays. Each compound serves as a competitive inhibitor and displays the expected inhibitory properties. Indeed, compound 4 and the cyclic phosphate 3 of 6-O-(2-hydroxyethyl)cyclohexane-1,2,4,6-tetraol are, respectively, the most potent examples of a primary alkyl phosphate inhibitor and a phosphate monoanion inhibitor yet reported for the enzyme. The stereochemistry of the most potent inhibitor, (1R,2R,4R,6R)-2 as deduced from the X-ray crystal structure of a synthetic precursor, provides useful mechanistic insight into the action of the enzyme and the mode of inhibitor binding.
Regiochemical control of the ring opening of aziridines by means of chelating processes. Synthesis and ring-opening reactions of cis- and trans-aziridines derived from 4-(benzyloxy)cyclohexene
Crotti,Favero,Gardelli,Macchia,Pineschi
, p. 2514 - 2525 (2007/10/02)
The regiochemical outcome of the ring opening of aziridines bearing a polar remote functionality was verified in a conformationally semirigid bicyclic system in which the polar functionality (OBn) is in an homoallylic relationship to the aziridine ring. T
Regiochemical Control of the Ring-Opening of 1,2-Epoxides by Means of Chelating Processes. Synthesis and Reactions of the cis- and trans-Oxides Derived from 4-(Benzyloxy)cyclohexene
Chini, Marco,Crotti, Paolo,Flippin, Lee A.,Macchia, Franco
, p. 4265 - 4272 (2007/10/02)
The synthesis and reactions of diastereomeric epoxides cis-1 and trans-2 with heteronucleophiles were carried out in order to probe the effect of remote polar functionality on the regioselectivity of nucleophilic addition to the epoxide ring.The reaction
Identification of (1S)-Phosphoryloxy-(2R,4S)-dihydroxycyclohexane as a Potent Inhibitor of Inositol Monophosphatase
Baker, Raymond,Leeson, Paul D.,Liverton, Nigel J.,Kulagowski, Janusz J.
, p. 462 - 464 (2007/10/02)
The 3,5,6-trisdeoxy derivative of myo-inositol 1-monophosphate, (1S)-phosphoryloxy-(2R,4S)-dihydroxycyclohexane , derived from the parent substrate by a strategy of hydroxy deletion, has been synthesised and shown to be the most potent inhibitor of inositol monophosphatase yet identified.
