1-(2-aminoethyl)-3-(arylsulfonyl)-1H-indoles as novel 5-HT6 receptor ligands

被引：47

作者：

Bernotas, R

Lenicek, S

Antane, S

Zhang, GM

Smith, D

Coupet, J

Harrison, B

Schechter, LE

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci, Collegeville, PA 19426 USA

[2] Wyeth Ayerst Res, Chem & Screening Sci, Princeton, NJ 08543 USA

[3] Wyeth Res, Neurosci, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 22期

关键词：

serotonin 5-HT6 indoles GPCR;

D O I：

10.1016/j.bmcl.2004.09.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 1-(2-aminoethyl)-3-(arylsulfonyl)-1H-indoles were prepared. Binding assays indicated they are 5-HT6 receptor ligands, among which N,N-dimethyl-N-{2-[3-(1-naphthylsulfonyl)-1H-indol-1-yl]ethyl}amine 8t and N-methyl-N-{2-[3-(1-naphthylsulfonyl)-1H-indol-1-yl]ethyl}amine 8u showed high affinity for 5-HT6 receptors with K-i = 3.7 and 5.7nM, respectively. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5499 / 5502

页数：4

相关论文

共 18 条

[1] Chloromethyl sulfones from sulfonyl chlorides via a one-pot procedure [J].

Antane, S ;

Bernotas, R ;

Li, YF ;

McDevitt, R ;

Yan, YF .

SYNTHETIC COMMUNICATIONS, 2004, 34 (13) :2443-2449

[2]

BERNOTAS RC, Patent No. 6727246

[3] OXIDATION OF THIOLS IN PRESENCE OF PYRROLES [J].

BEVERIDGE, S ;

HARRIS, RLN .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1971, 24 (06) :1229-+

[4] Novel agonists of 5HT(2C) receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methylethylamines. Improved therapeutics for obsessive compulsive disorder [J].

Bos, M ;

Jenck, F ;

Martin, JR ;

Moreau, JL ;

Sleight, AJ ;

Wichmann, J ;

Widmer, U .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (17) :2762-2769

[5]

BOURDAIS J, 1974, EUR J MED CHEM, V9, P269

[6] 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

[7] SYNTHESIS OF N-(AMINOETHYL)AZOLES UNDER PHASE-TRANSFER CATALYSIS [J].

CUADRO, AM ;

MATIA, MP ;

GARCIA, JL ;

VAQUERO, JJ ;

ALVAREZBUILLA, J .

SYNTHETIC COMMUNICATIONS, 1991, 21 (04) :535-544

[8] Higher-end serotonin receptors:: 5-HT5, 5-HT6, and 5-HT7 [J].

Glennon, RA .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (14) :2795-2812

[9] Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-bioavailable 5-HT1D agonists [J].

Isaac, M ;

Slassi, M ;

Xin, T ;

Arora, J ;

O'Brien, A ;

Edwards, L ;

MacLean, N ;

Wilson, J ;

Demschyshyn, L ;

Labrie, P ;

Naismith, A ;

Maddaford, S ;

Papac, D ;

Harrison, S ;

Wang, H ;

Draper, S ;

Tehim, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (24) :4409-4413

[10] SERIES REACTIONS OF ORGANIC-ANIONS .114. SPECIFIC ORTHO-ORIENTATION IN THE VICARIOUS SUBSTITUTION OF HYDROGEN IN AROMATIC NITRO-COMPOUNDS WITH CARBANION OF CHLOROMETHYL PHENYL SULFONE [J].

MAKOSZA, M ;

GLINKA, T ;

KINOWSKI, A .

TETRAHEDRON, 1984, 40 (10) :1863-1868