Synthesis of conformationally restricted analogs of baclofen, a potent GABAB receptor agonist, by the introduction of a cyclopropane ring. |
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Authors: | S Shuto N Shibuya S Yamada T Ohkura R Kimura A Matsuda |
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Institution: | Graduate School of Pharmaceutical Science, Hokkaido University, Sapporo, Japan. |
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Abstract: | Conformationally restricted analogs of baclofen (2), i.e., 5, 6, and their enantiomers ent-5, and ent-6, the conformations of which were restricted by introducing a cyclopropane ring, were designed as potential GABAB receptor ligands. Reaction of (R)-epichlorohydrin (R)-7] and (4-chlorophenyl)acetonitrile in the presence of NaNH2 in benzene/tetrahydrofuran gave chiral cyclopropane derivatives 11 and 12, which were then converted into the target compounds 5 and 6, respectively. Their corresponding enantiomers, ent-5 and ent-6, were also synthesized starting from (S)-epichlorohydrin (S)-7]. |
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