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Design and synthesis of morpholine derivatives. SAR for dual serotonin & noradrenaline reuptake inhibition.

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Fish PV,Deur C,Gan X,Greene K,Hoople D,Mackenny M,Para KS,Reeves K,Ryckmans T,Stiff C,Stobie A,Wakenhut F,Whitlock GA

doi

10.1016/j.bmcl.2008.03.050

subject

Has Abstract

pub_date

2008-04-15 00:00:00

pages

2562-6

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)00323-5

journal_volume

18

pub_type

杂志文章

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