Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist.
To assess the stereochemical requirements for efficient alpha2C-adrenoreceptor activation, the enantiomeric forms of m-nitrobiphenyline [(+/-)-5] were prepared and tested on cells expressing the human alpha2-adrenoreceptor subtypes. The importance of chirality was confirmed, since the enantiomer (R)-(+)-5 was much more efficient than (S)-(-)-5 in producing alpha2C-activation. Surprising reversal of enantioselectivity was observed with respect to structurally similar biphenyline [(+/-)-1] whose (S)-(-)-form proved the preferred alpha2C-configuration.
Crassous
Pierre-Antoine
PA
Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Via S. Agostino 1, 62032 Camerino, Italy.
Cardinaletti
Claudia
C
Carrieri
Antonio
A
Bruni
Bruno
B
Di Vaira
Massimo
M
Gentili
Francesco
F
Ghelfi
Francesca
F
Giannella
Mario
M
Paris
Hervé
H
Piergentili
Alessandro
A
Quaglia
Wilma
W
Schaak
Stéphane
S
Vesprini
Cristian
C
Pigini
Maria
M
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D013237:Stereoisomerism
C524114:3-nitrobiphenyline; D058647:Adrenergic alpha-2 Receptor Agonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D000242:Cyclic AMP