847805-33-8Relevant articles and documents
Stereodivergent synthesis of all the four stereoisomers of antidepressant reboxetine
Liu, Cheng,Lin, Zhi-Wei,Zhou, Zhao-Hui,Chen, Hong-Bin
, p. 5395 - 5401 (2017/07/10)
Chiral amino alcohol-copper(ii) catalysts Cu-L1c and Cu-ent-L1c were utilized to promote the diastereoselective nitroaldol reactions of chiral aldehydes (S)-3 or (R)-3 with nitromethane, which respectively led to the preferential formation of certain stereoisomer for nitro diol derivatives 4. Using this catalytic protocol, all the four stereoisomers of the antidepressant reboxetine were divergently prepared. The highest overall yield of this synthetic route reached up to 30.5% from aldehyde (S)-3.
Enantioselective synthesis of (R)- and (S)-N-Boc-morpholine-2-carboxylic acids by enzyme-catalyzed kinetic resolution: application to the synthesis of reboxetine analogs
Fish, Paul V.,Mackenny, Malcolm,Bish, Gerwyn,Buxton, Timothy,Cave, Russell,Drouard, David,Hoople, David,Jessiman, Alan,Miller, Duncan,Pasquinet, Christelle,Patel, Bhairavi,Reeves, Keith,Ryckmans, Thomas,Skerten, Melanie,Wakenhut, Florian
body text, p. 389 - 391 (2009/05/11)
The (R)- and (S)-N-Boc-morpholine-2-carboxylic acids 9 and 10 were prepared using an enantioselective synthesis employing a highly selective enzyme-catalyzed kinetic resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (11) as the key step. Acids 9 and 10 were then converted efficiently and stereoselectively to reboxetine analogs 3 and 4.
Syntheses of (S,S)-reboxetine via a catalytic stereospecific rearrangement of β-amino alcohols
Metro, Thomas-Xavier,Pardo, Domingo Gomez,Cossy, Janine
, p. 707 - 710 (2008/09/17)
(Chemical Equation Presented) The formal total synthesis of (S,S)-reboxetine has been realized by two different approaches using a stereospecific rearrangement of β-amino alcohols catalyzed by (CF 3CO)2O.
Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition
Fish, Paul V.,Deur, Christopher,Gan, Xinmin,Greene, Keri,Hoople, David,Mackenny, Malcolm,Para, Kimberly S.,Reeves, Keith,Ryckmans, Thomas,Stiff, Cory,Stobie, Alan,Wakenhut, Florian,Whitlock, Gavin A.
, p. 2562 - 2566 (2008/12/21)
Single enantiomer (SS) and (RR) 2-[(phenoxy)(phenyl)methyl]morpholine derivatives 5, 8-23 are inhibitors of monoamine reuptake. Target compounds were prepared using an enantioselective synthesis employing a highly specific enzyme-catalysed resolution of racemic n-butyl 4-benzylmorpholine-2-carboxylate (26) as the key step. Structure-activity relationships established that serotonin and noradrenaline reuptake inhibition are functions of stereochemistry and aryl/aryloxy ring substitution. Consequently, selective SRI, selective NRI and dual SNRIs were all identified. One of these compounds, a potent and selective dual SNRI, (SS)-5a was selected as a candidate for further pre-clinical evaluation.
Design and synthesis of reboxetine analogs morpholine derivatives as selective norepinephrine reuptake inhibitors
Xu, Wenjian,Gray, David L.,Glase, Shelly A.,Barta, Nancy S.
scheme or table, p. 5550 - 5553 (2009/05/30)
As part of a discovery effort aimed at identifying novel norepinephrine reuptake inhibitors (NRIs), a number of substituted morpholines were designed and synthesized. The target compounds contain vicinal stereogenic centers, and the program was greatly facilitated by the adoption of efficient synthetic routes which allowed for the late stage incorporation of structural and physicochemical diversity into the targets. Structure-activity relationships were developed by optimizing individual ring components of the structure for NRI potency and for selectivity against other monoamine reuptake transporters. Several novel morpholine derivatives with a potent and selective NRI profile are described.
Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER
Tamagnan, Gilles D.,Brenner, Eric,Alagille, David,Staley, Julie K.,Haile, Colin,Koren, Andrei,Early, Michelle,Baldwin, Ronald M.,Tarazi, Frank I.,Baldessarini, Ross J.,Jarkas, Nachwa,Goodman, Mark M.,Seibyl, John P.
, p. 533 - 537 (2007/10/03)
A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT im
NOREPINEPHRINE TRANSPORTER RADIOTRACERS AND METHODS OF SYNTHESES THEREOF
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Page/Page column 53, (2008/06/13)
The present invention provides compounds and radiotracers thereof for locating, diagnosing, identifying, evaluating, detecting or quantitating NET by in vivo imaging. The invention also provides methods for locating, diagnosing, identifying, evaluating, detecting or quantitating NET, using radiotracers of high-affinity or labeled compounds of the invention, which exhibit low toxicity, can cross the blood-brain barrier and, preferably, distinguish among normal and abnormal brains. For example, a radiotracer of the invention can be administered to a patient in an amount suitable for in vivo imaging thereof. Preferably, radiotracers of the invention can also be used to locate, diagnosis, identify, evaluate, detect and quantitate NET in such diseases, disorders, conditions or maladies as, without limitation, depression, anxiety, ADHD and drug dependency.
Novel compounds
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Page/Page column 51, (2010/02/14)
The present invention provides compounds of Formula I wherein R1, R2, R3, and n have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment
Asymmetric synthesis of (+)-(S,S)-reboxetine via a new (S)-2- (hydroxymethyl)morpholine preparation
Brenner, Eric,Baldwin, Ronald M.,Tamagnan, Gilles
, p. 937 - 939 (2007/10/03)
(Chemical Equation Presented) (S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99% ee in eight steps. Key steps were selective oxidation of an N-protected hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic substitution.
