1421-89-2Relevant articles and documents
A perturbed pKa at the binding site of the nicotinic acetylcholine receptor: Implications for nicotine binding
Petersson, E. James,Choi, Anita,Dahan, David S.,Lester, Henry A.,Dougherty, Dennis A.
, p. 12662 - 12663 (2002)
A series of tethered quaternary ammonium derivatives of Tyr have been incorporated into the binding site of the nicotinic acetylcholine receptor (nAChR) using the in vivo nonsense suppression method, producing constitutively active (self-gating) receptors. We have incorporated primary, secondary, and tertiary amine tethered agonists to give receptors whose constitutive activity can be modulated by pH. Lowering the pH protonates the tethered amine, giving it a positive charge and allowing it to reversibly activate the receptor. Tertiary and secondary tethered amines, TyrO3T and TyrO3S, have been successfully incorporated at α149 in the nAChR. Constitutive currents at pH 5.5 are 6 times those at pH 9.0. The pKa of TyrO3T in the binding site appears to be 6 or lower, differing substantially from its pKa in solution (～9.3). This local pKa perturbation has substantial implications for pharmacological research on the nAChR: of the tertiary agonists considered, noracetylcholine experiences this pKa perturbation, while nicotine does not. Copyright
Design, synthesis and biological evaluation of choline based SPECT imaging agent: Ga(iii)-DO3A-EA-Choline
Uppal, Jasleen K.,Hazari, Puja P.,Raunak,Chuttani, Krishna,Allard, Michele,Kaushik, Narender K.,Mishra, Anil K.
, p. 1591 - 1599 (2011)
The enhanced choline uptake and phosphorylation in tumor cells has motivated the development of radiolabeled choline derivatives as diagnostic markers for imaging cell membrane proliferation and noninvasive detection of prostate, brain and breast tumors. In the present work, we report a facile strategy for the synthesis of choline functionalized macrocyclic chelating agent (DO3A-EA-choline) and its radiocomplexation with 67Ga for potential tumor imaging applications. The synthesis of the desired compound featured quaternization of N,N-dimethylaminoethanol with 1,2-dibromoethane followed by subsequent alkylation with trisubstituted cyclen (DO3A). All intermediates and final compounds have been fully characterized by spectroscopic techniques, namely, 1H, 13C NMR and mass spectroscopy. The compound has been successively labeled with 67Ga-citrate in ammonium acetate buffer (pH 6.5) at 80 °C. MTT assays have been performed on the HEK cell line to determine the cytotoxicity of the compound. Cell uptake studies carried out on the U-87 MG cell line exhibited saturable binding of the radioconjugate in picomolar range with a Kd value of 0.528 pM. The in vivo biodistribution and blood kinetics studies exhibited rapid clearance of the radiolabeled complex and excretion through the renal and hepatobiliary route. The present studies demonstrate the potential applications of 67Ga-DO3A-EA-choline as a radiopharmaceutical for molecular imaging using (67/68Ga) SPECT and PET modalities. The Royal Society of Chemistry 2011.
Sulfur and nitrogen mustard carbonate analogues
Arico, Fabio,Chiurato, Matteo,Peltier, Josephine,Tundo, Pietro
experimental part, p. 3223 - 3228 (2012/07/31)
Sulfur and nitrogen half-mustard compounds lose their aggressive properties when the chlorine atom is replaced by a carbonate moiety. The anchimeric effect of the novel mustard carbonate analogues is investigated. The reaction follows first-order kinetics, does not need any base, and occurs with -OH, -NH and acidic -CH nucleophiles. Most of these molecules are unexplored and might provide a novel strategy for the preparation of compounds previously not easily accessible. Copyright
Room temperature ionic liquids - New choline derivatives
Pernak,Chwala,Syguda
, p. 539 - 546 (2007/10/03)
New room temperature ionic liquids - choline derivatives were prepared by Menschutkin reaction with alkyl chloromethyl ethers and anion changed to bis(trifluoromethylsulfonyl)amide ion. The newly obtained butoxymethyl(2-hydroxyethyl)dimethylammonium bis(trifluoromethanesulfonyl)amide was successfully tested as a solvent for O-acylation in two-phase reaction system. The ionic liquid-catalyst system was recycled and reused.
Synthesis and characterization of photolabile compounds releasing noracetylcholine in the microsecond time range
Peng,Wirz,Goeldner
, p. 398 - 400 (2007/10/03)
The rapid and efficient photochemical release of noracetylcholine 2, an analogue of the neurotransmitter acetylcholine, from its precursor 1 makes this probe well-suited for a dynamic study of the mechanism of hydrolysis of acetylcholine by acetylcholinesterase. The nitrobenzyl derivative 1, the most promising candidate for time-resolved crystallographic studies of this rapid enzyme, displays the required photo-fragmentation kinetics in the microsecond time-range and inhibitory properties oacetylcholinesterase.
O-ACYLATION OF 2-(DIMETHYLAMINO)-1-ETHANOL BY p-NITROPHENYL ESTERS OF N-SUBSTITUTED AMINO ACID
Topuzyan, V. O.,Alebyan, G. P.,Mndzhoyan, O. L.
, p. 733 - 737 (2007/10/02)
The kinetics of the O-acylation of 2-(dimethylamino)-1-ethanol by the p-nitrophenyl ester of N-(benzyloxycarbonyl)amino acids and also benzoylaminoacetic, acetic, and chloroacetic acids were studied.The rate constants of the pseudofirst-order reaction wer
Dimethylamino derivatives and their use
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, (2008/06/13)
(Dimethylaminoalkyl)carboxylic and -carbamic acid esters and (dimethylaminoalkyl) ethers and ureas are compounds which are especially suitable for use as amine curing agents for polyepoxide compounds. They impart longer curing times to the curable mixtures and thus good processing properties, especially when the mixtures are used as adhesives. In addition, the mechanical properties are often improved. Further, these compounds afford advantages when used as curing agents on account of their low volatility.
