2. Academic Validation
  3. Identification of anxiolytic/nonsedative agents among indol-3-ylglyoxylamides acting as functionally selective agonists at the gamma-aminobutyric acid-A (GABAA) alpha2 benzodiazepine receptor

Identification of anxiolytic/nonsedative agents among indol-3-ylglyoxylamides acting as functionally selective agonists at the gamma-aminobutyric acid-A (GABAA) alpha2 benzodiazepine receptor

  • J Med Chem. 2009 Jun 25;52(12):3723-34. doi: 10.1021/jm9001154.
Sabrina Taliani 1,  Barbara Cosimelli,  Federico Da Settimo,  Anna Maria Marini,  Concettina La Motta,  Francesca Simorini,  Silvia Salerno,  Ettore Novellino,  Giovanni Greco,  Sandro Cosconati,  Luciana Marinelli,  Francesca Salvetti,  Gianluca L'Abbate,  Silvia Trasciatti,  Marina Montali,  Barbara Costa,  Claudia Martini
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, 56126 Pisa, Italy. barbara.cosimelli@unina.it
PMID: 19469479 DOI: 10.1021/jm9001154
Abstract

Anxioselective agents may be identified among compounds binding selectively to the alpha(2)beta(x)gamma(2) subtype of the gamma-aminobutyric acid-A (GABA(A))/central benzodiazepine receptor (BzR) complex and behaving as agonists or among compounds binding with comparable potency to various BzR subtypes but eliciting agonism only at the alpha(2)beta(x)gamma(2) receptor. Because of subtle steric differences among BzR subtypes, the latter approach has proved much more successful. A biological screening within the class of indol-3-ylglyoxylamides 1-3 allowed us to identify compounds 1c and 2b as potential anxiolytic/nonsedative agents showing alpha(2) selective efficacy in vitro and anxioselective effects in vivo. According to molecular modeling studies, and consistently with SARs accumulated in the past decade, 5-NO(2)- and 5-H-indole derivatives would preferentially bind to BzR by placing the indole ring in the L(Di) and the L(2) receptor binding sites, respectively.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z