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Synthesis 2018; 50(20): 4124-4132
DOI: 10.1055/s-0037-1610211
paper
© Georg Thieme Verlag Stuttgart · New York

Improved Synthesis of Anxiolytic, Anticonvulsant, and Antinociceptive α2/α3-GABA(A)-ergic Receptor Subtype Selective Ligands as Promising Agents to Treat Anxiety, Epilepsy, and Neuropathic Pain

Guanguan Li 
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA   eMail: capncook@uwm.edu
,
Lalit K. Golani
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA   eMail: capncook@uwm.edu
,
Rajwana Jahan
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA   eMail: capncook@uwm.edu
,
Farjana Rashid
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA   eMail: capncook@uwm.edu
,
James M. Cook*
Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA   eMail: capncook@uwm.edu
› InstitutsangabenWe would like to thank the NIH for generous financial support (MH096463, NS076517).
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Publikationsverlauf

Received: 04. Juni 2018

Accepted after revision: 06. Juni 2018

Publikationsdatum:
24. Juli 2018 (online)

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Abstract

An improved synthesis of the anxiolytic, anticonvulsant, and antinociceptive compounds: Hz-166, and its bioisosteres 1,2,4-oxadiazole (MP-III-080) and 1,3-oxazole (KRM-II-81) were synthesized in higher yields and with more facile purification methods (crystallization, etc.) in multigram quantities without column chromatography. In the synthesis of KRM-II-81, an alternative procedure was employed using the selective reducing reagent, potassium diisobutyl-tert-butoxyaluminum hydride (PDBBA), to prepare the desired C(3)-aldehyde in the absence of N(5)–C(6) imine reduction in good yield on a 20 gram scale.

Key words

GABAAR - benzodiazepines - anxiety - epilepsy - neuropathic pain - large scale - imine - selective reduction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610211.
  • Supporting Information
 

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