1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor

被引：127

作者：

Porter, RA

Chan, WN

Coulton, S

Johns, A

Hadley, MS

Widdowson, K

Jerman, JC

Brough, SJ

Coldwell, M

Smart, D

Jewitt, F

Jeffrey, P

Austin, N

机构：

[1] GlaxoSmithKline, Harlow CM19 5AW, Essex, England

[2] GlaxoSmithKline, King Of Prussia, PA 19406 USA

[3] GlaxoSmithKline, Welwyn Garden City AL6 9AR, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(01)00343-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This communication reports SARs for the first orexin-1 receptor antagonist series of 1-aryl-3-quifiolin-4-yl and 1-aryl-3-naphthyridin-4-yl ureas. One of these compounds, 31 (5B-334867), has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing. (C) 2001 Elsevier Science Ltd. All rights reserved.

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页码：1907 / 1910

页数：4

相关论文

共 17 条

[1] SYNTHESIS OF ANTIMALARIALS .6. SYNTHESIS OF CERTAIN 1,5-NAPHTHYRIDINE AND 1,8-NAPHTHYRIDINE DERIVATIVES [J].

ADAMS, JT ;

BRADSHER, CK ;

BRESLOW, DS ;

AMORE, ST ;

HAUSER, CR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1946, 68 (07) :1317-1319

[2] Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents:: Synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines [J].

Bromidge, SM ;

Dabbs, S ;

Davies, DT ;

Duckworth, DM ;

Forbes, IT ;

Ham, P ;

Jones, GE ;

King, FD ;

Saunders, DV ;

Starr, S ;

Thewlis, KM ;

Wyman, PA ;

Blaney, FE ;

Naylor, CB ;

Bailey, F ;

Blackburn, TP ;

Holland, V ;

Kennett, GA ;

Riley, GJ ;

Wood, MD .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (10) :1598-1612

[3]

Chan G., 1999, Phenyl Urea and Phenyl Thiourea Derivatives as HFGAN72 Antagonists, Patent No. [WO9909024, 9909024]

[4] Pressor effects of orexins injected intracisternally and to rostral ventrolateral medulla of anesthetized rats [J].

Chen, CT ;

Hwang, LL ;

Chang, JK ;

Dun, NJ .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2000, 278 (03) :R692-R697

[5] Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement [J].

Duxon, MS ;

Stretton, J ;

Starr, K ;

Jones, DNC ;

Holland, V ;

Riley, G ;

Jerman, J ;

Brough, S ;

Smart, D ;

Johns, A ;

Chan, W ;

Porter, RA ;

Upton, N .

PSYCHOPHARMACOLOGY, 2001, 153 (02) :203-209

[6] B3LYP density functional calculations of 1H and 13C nuclear shielding constants of some unsymmetric N,N′-dipyridyl ureas and a further insight into their molecular conformations [J].

Ferraro, MB .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 528 :199-209

[7] Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat [J].

Haynes, AC ;

Jackson, B ;

Overend, P ;

Buckingham, RE ;

Wilson, S ;

Tadayyon, M ;

Arch, JRS .

PEPTIDES, 1999, 20 (09) :1099-1105

[8] A selective orexin-1 receptor antagonist reduces food consumption in male and female rats [J].

Haynes, AC ;

Jackson, B ;

Chapman, H ;

Tadayyon, M ;

Johns, A ;

Porter, RA ;

Arch, JRS .

REGULATORY PEPTIDES, 2000, 96 (1-2) :45-51

[9]

Johns A., 1999, Patent No. [WO99/58533 A1, 9958533]

[10] The novel brain neuropeptide, orexin-A, modulates the sleep-wake cycle of rats [J].

Piper, DC ;

Upton, N ;

Smith, MI ;

Hunter, AJ .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (02) :726-730