Benzimidazoles as new potent and selective DP antagonists for the treatment of allergic rhinitis

被引:73
作者
Beaulieu, C [1 ]
Wang, ZY [1 ]
Denis, D [1 ]
Greig, G [1 ]
Lamontagne, S [1 ]
O'Neill, G [1 ]
Slipetz, D [1 ]
Wang, J [1 ]
机构
[1] Merck Frosst Ctr Therapeut Res, Kirkland, PQ H9R 4P8, Canada
关键词
benzimidazole; DP antagonist;
D O I
10.1016/j.bmcl.2004.04.005
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of 2-substituted N-benzyl benzimidazole containing molecules has been synthesized and its structure-activity relationship for the human DP receptor has been evaluated. Selective DP antagonists with nanomolar potency for the DP receptor were identified in this novel series of benzimidazoles. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3195 / 3199
页数:5
相关论文
共 12 条
[1]   The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs [J].
Abramovitz, M ;
Adam, M ;
Boie, Y ;
Carrière, MC ;
Denis, D ;
Godbout, C ;
Lamontagne, S ;
Rochette, C ;
Sawyer, N ;
Tremblay, NM ;
Belley, M ;
Gallant, M ;
Dufresne, C ;
Gareau, Y ;
Ruel, R ;
Juteau, H ;
Labelle, M ;
Ouimet, N ;
Metters, KM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1483 (02) :285-293
[2]  
Arimura A, 2001, J PHARMACOL EXP THER, V298, P411
[3]   MOLECULAR-CLONING AND CHARACTERIZATION OF THE HUMAN PROSTANOID DP RECEPTOR [J].
BOIE, Y ;
SAWYER, N ;
SLIPETZ, DM ;
METTERS, KM ;
ABRAMOVITZ, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (32) :18910-18916
[4]  
CHARLESWORTH EN, 1991, J IMMUNOL, V146, P671
[5]   PHYSIOLOGICAL-RESPONSES TO INTRANASAL DOSE-RESPONSE CHALLENGES WITH HISTAMINE, METHACHOLINE, BRADYKININ, AND PROSTAGLANDIN IN ADULT VOLUNTEERS WITH AND WITHOUT NASAL ALLERGY [J].
DOYLE, WJ ;
BOEHM, S ;
SKONER, DP .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1990, 86 (06) :924-935
[6]   Mediators of nasal blockage in allergic rhinitis [J].
Howarth, PH .
ALLERGY, 1997, 52 :12-18
[7]   RELEASE OF PROSTAGLANDIN-D2 INTO HUMAN AIRWAYS DURING ACUTE ANTIGEN CHALLENGE [J].
MURRAY, JJ ;
TONNEL, AB ;
BRASH, AR ;
ROBERTS, LJ ;
GOSSET, P ;
WORKMAN, R ;
CAPRON, A ;
OATES, JA .
NEW ENGLAND JOURNAL OF MEDICINE, 1986, 315 (13) :800-804
[8]  
NACLERIO RM, 1983, AM REV RESPIR DIS, V128, P597
[9]   INFLAMMATORY MEDIATORS IN LATE ANTIGEN-INDUCED RHINITIS [J].
NACLERIO, RM ;
PROUD, D ;
TOGIAS, AG ;
ADKINSON, NF ;
MEYERS, DA ;
KAGEYSOBOTKA, A ;
PLAUT, M ;
NORMAN, PS ;
LICHTENSTEIN, LM .
NEW ENGLAND JOURNAL OF MEDICINE, 1985, 313 (02) :65-70
[10]   Synthesis of 2-(alkylamino)benzimidazoles [J].
Perkins, JJ ;
Zartman, AE ;
Meissner, RS .
TETRAHEDRON LETTERS, 1999, 40 (06) :1103-1106