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Synthesis, stereochemistry, and opioid receptor binding activity of heterocyclic analogues of BW373U86
Author(s) -
Boswell G. Evan,
Mcnutt Robert W.,
Bubacz Dulce G.,
Davis Ann O.,
Chang KwenJen
Publication year - 1995
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570320622
Subject(s) - chemistry , thionyl chloride , phenylmagnesium bromide , benzaldehyde , diastereomer , alkylation , benzyl bromide , stereochemistry , organic chemistry , medicinal chemistry , chloride , catalysis , reagent
The synthesis of a series of heterocyclic analogues of (±)‐4‐((α R *)‐α‐((2 S *,5 R *)‐4‐allyl‐2,5‐dimethyl‐1‐piperazmyl)‐3‐hydroxybenzyl)‐ N,N ‐diethylbenzarrude (BW373U86) for screening against opioid receptors is described. The intermediate α‐heterocyclic benzyl alcohols 24 were synthesized either by low temperature reaction of lithioheterocycles with 3‐(( tert ‐butyldimethylsilyl)oxy)benzaldehyde ( 10 ) or by reaction of 3‐(( tert ‐butyldimethylsilyl)oxy)phenylmagnesium bromide ( 19 ) with heterocyclic carbaldehydes. The α‐heterocyclic benzyl alcohols 24 were converted to chloromethines ( 25 ) with thionyl chloride and used to alkylate with trans ‐1‐allyl‐2,5‐dimethylpiperazine ( 5 ) to give diastereomeric pairs of the target compounds. The bromoheterocycles were then derivatized to produce amides. Compounds that are potent and selective for the 5 or μ opioid receptors and some mixed δ/μ analogues are reported.