[EN] ALPHA, OMEGA-DICARBOXIMIDE DERIVATIVES AS USEFUL URO-SELECTIVE Alpha1Alpha ADRENOCEPTOR BLOCKERS<br/>[FR] DERIVES D'ALPHA, OMEGA-DICARBOXIMIDE UTILES EN TANT QU'INHIBITEURS UROSELECTIFS DE L'ADRENO-RECEPTEUR <1?
申请人:RANBAXY LAB LTD
公开号:WO2003084928A1
公开(公告)日:2003-10-16
Novel α,ω-dicarboximide derivatives which selectively inhibit binding to the α-1A adrenergic receptor, a receptor which has been shown to be important in the treatment of benign prostatic hyperplasia. The compounds of the present invention are potentially useful in the treatment of benign prostatic hyperplasia.
The invention provides novel GlyT2 inhibiting compounds useful in modulating, treating, or preventing: anxiolytic disorders; a condition requiring treatment of injured mammalian nerve tissue; a condition amenable to treatment through administration of a neurotrophic factor; a neurological disorder; or obesity; an obesity-related disorder.
Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives
作者:Ronald L Wolin、Alejandro Santillán、Liu Tang、Charles Huang、Xiaoxia Jiang、Timothy W Lovenberg
DOI:10.1016/j.bmc.2004.05.044
日期:2004.8
A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [C-14]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in GlyT-2 inhibitory activity. In contrast, the distal aryl ring was more tolerant to functional group modifications and could accommodate a variety of substitutes at the C-2 or C-3 positions. Comparable activities to 4a were obtained by replacing the anilino nitrogen with an ether linkage 27 or by exchanging the isopropoxy ether moiety with an isopropyl amino group 15. A distinct preference for a 2-carbon tether (n = 1) was observed relative to the corresponding 3-carbon homolog (n = 2). (C) 2004 Elsevier Ltd. All rights reserved.