HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.
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Page 25
(2010/02/07)
Rapid Scan UV Spectroscopic and Kinetic Studies of the Reaction of Methyl 4-Methoxy-3,5-dinitrobenzoate with Pyrrolidine in Dimethyl Sulfoxide
An intermediate complex in the aromatic nucleophilic substitution reaction of methyl 4-methoxy-3,5-dinitrobenzoate with pyrrolidine in dimethyl sulfoxide has been observed by rapid scan UV spectroscopy, and kinetic and equilibrium constants have been obtained for its formation and decomposition.The observable intermediate is the conjugate base (I-) of the zwitterionic form (IH).The formation of I- is base catalyzed and the decomposition of I- is first order in pyrrolidine hydrochloride.The possible mechanism is that proton transfer between IH and I- is not more rapid than the k-1 step and that general acid catalyzed leaving group departure from I- is rate limiting.
Hasegawa, Yoshinori
p. 649 - 652
(2007/10/02)
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