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Synthesis of chiral GABAA receptor subtype selective ligands as potential agents to treat schizophrenia as well as depression.
Li, Guanguan; Stephen, Michael R; Kodali, Revathi; Zahn, Nicolas M; Poe, Michael M; Tiruveedhula, V V N Phani Babu; Huber, Alec T; Schussman, Melissa K; Qualmann, Krista; Panhans, Cristina M; Raddatz, Nicholas J; Baker, David A; Prevot, Thomas D; Banasr, Mounira; Sibille, Etienne; Arnold, Leggy A; Cook, James M.
Afiliação
  • Li G; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Stephen MR; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Kodali R; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Zahn NM; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Poe MM; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Tiruveedhula VVNPB; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Huber AT; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Schussman MK; Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
  • Qualmann K; Department of Biomedical Science, Marquette University, Milwaukee, Wisconsin 53233, United States.
  • Panhans CM; Department of Biomedical Science, Marquette University, Milwaukee, Wisconsin 53233, United States.
  • Raddatz NJ; Department of Biomedical Science, Marquette University, Milwaukee, Wisconsin 53233, United States.
  • Baker DA; Department of Biomedical Science, Marquette University, Milwaukee, Wisconsin 53233, United States.
  • Prevot TD; Campbell Family Mental Health Research Institute of CAMH, Toronto, Canada.
  • Banasr M; Campbell Family Mental Health Research Institute of CAMH, Toronto, Canada.
  • Sibille E; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
  • Arnold LA; Department of Psychiatry, University of Toronto, Toronto, Canada.
  • Cook JM; Campbell Family Mental Health Research Institute of CAMH, Toronto, Canada.
ARKIVOC ; 2018(4): 158-182, 2018.
Article em En | MEDLINE | ID: mdl-32774192
ABSTRACT
A series of novel imidazobenzodiazepine analogs of the lead chiral ligand SH-053-2'F-S-CH3 (2), an α2/α3/α5 (Bz)GABA (A)ergic receptor subtype selective ligand, which reversed PCP-induced prepulse inhibition (PPI) of acoustic startle, were synthesized. These chiral (S)-CH3 ligands are targeted for the treatment of schizophrenia and depression. These new ligands were designed by modifying the liable ester functionality in 2 to improve the metabolic stability, cytotoxicity, and activity as compared to 2. Based on the data to date, the most promising ligands are the N-cyclopropyl amide GL-I-55 (8c) and the methyl bioisostere GL-I-65 (9a). The in vitro metabolic stability, cytotoxicity and in vivo locomotor effects are described in this report. Based on these results, 8c and 9a are the most promising for further in vivo pharmacology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ARKIVOC Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ARKIVOC Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos