N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists

被引：43

作者：

Cole, DC ^{[1
]}

Ellingboe, JW

Lennox, WJ

Mazandarani, H

Smith, DL

Stock, JR

Zhang, GM

Zhou, P

Schechter, LE

机构：

[1] Wyeth Res, Pearl River, NY 10965 USA

[2] Wyeth Res, Princeton, NJ 08852 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 02期

关键词：

5-HT6; antagonists; 5-hydroxytryptamine(6) antagonists;

D O I：

10.1016/j.bmcl.2004.10.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of Ni-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)indole derivatives was designed and synthesized. These compounds were shown to have high affinity for the 5-HT6 receptor. Two analogs, 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-1-sulfonyl]-phenylamine 15g and 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-5-methoxy-1H-indole-1-sulfonyl]-phenylamine 15y, had 0.4 and 3.0nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：379 / 383

页数：5

相关论文

共 19 条

[1] 3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 5-HT RECEPTOR-BINDING DATA FOR TETRAHYDROPYRIDINYLINDOLE DERIVATIVES - A COMPARISON OF THE HANSCH AND COMFA METHODS [J].

AGARWAL, A ;

PEARSON, PP ;

TAYLOR, EW ;

LI, HB ;

DAHLGREN, T ;

HERSLOF, M ;

YANG, YH ;

LAMBERT, G ;

NELSON, DL ;

REGAN, JW ;

MARTIN, AR .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (25) :4006-4014

[2] 5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide (SB-271046):: A potent, selective, and orally bioavailable 5-HT6 receptor antagonist [J].

Bromidge, SM ;

Brown, AM ;

Clarke, SE ;

Dodgson, K ;

Gager, T ;

Grassam, HL ;

Jeffrey, PM ;

Joiner, GF ;

King, FD ;

Middlemiss, DN ;

Moss, SF ;

Newman, H ;

Riley, G ;

Routledge, C ;

Wyman, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (02) :202-205

[3] Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists:: Identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134) [J].

Bromidge, SM ;

Clarke, SE ;

Gager, T ;

Griffith, K ;

Jeffrey, P ;

Jennings, AJ ;

Joiner, GF ;

King, FD ;

Lovell, PJ ;

Moss, SF ;

Newman, H ;

Riley, G ;

Rogers, D ;

Routledge, C ;

Serafinowska, H ;

Smith, DR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (01) :55-58

[4]

FILLA SA, 2004, Patent No. 0102481

[5] 2-Substituted tryptamines:: Agents with selectivity for 5-HT6 serotonin receptors [J].

Glennon, RA ;

Lee, M ;

Rangisetty, JB ;

Dukat, M ;

Roth, BL ;

Savage, JE ;

McBride, A ;

Rauser, L ;

Hufeisen, S ;

Lee, DKH .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (05) :1011-1018

[6] Characterization of [125I]-SB-258585 binding to human recombinant and native 5-HT6 receptors in rat, pig and human brain tissue [J].

Hirst, WD ;

Minton, JAL ;

Bromidge, SM ;

Moss, SF ;

Latter, AJ ;

Riley, G ;

Routledge, C ;

Middlemiss, DN ;

Price, GW .

BRITISH JOURNAL OF PHARMACOLOGY, 2000, 130 (07) :1597-1605

[7]

HOYER D, 1994, PHARMACOL REV, V46, P157

[8]

Kohen R, 1996, J NEUROCHEM, V66, P47

[9] Possible differences in modes of agonist and antagonist binding at human 5-HT6 receptors [J].

Pullagurla, MR ;

Westkaemper, RB ;

Glennon, RA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (17) :4569-4573

[10] N1-benzenesulfonylgramine and N1-benzenesulfonylskatole:: Novel 5-HT6 receptor ligand templates [J].

Pullagurla, MR ;

Dukat, M ;

Setola, V ;

Roth, B ;

Glennon, RA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (19) :3355-3359