The impact of spacer structure on 5-HT7 and 5-HT1A receptor affinity in the group of long-chain arylpiperazine ligands

被引：34

作者：

Bojarski, AJ

Duszynska, B

Kolaczkowski, M

Kowalski, P

Kowalska, T

机构：

[1] Polish Acad Sci, Inst Pharmacol, Dept Med Chem, PL-31343 Krakow, Poland

[2] Jagiellonian Univ, Coll Med, Dept Pharmaceut Chem, PL-30688 Krakow, Poland

[3] Krakow Tech Univ, Inst Organ Chem & Technol, PL-31155 Krakow, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 23期

关键词：

long-chain arylpiperazines; 5-HT7 receptor ligands; conformational constraints;

D O I：

10.1016/j.bmcl.2004.09.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New cis-, trans-2-butene and 1,2-bismethylbenzene analogues of MM77 and NAN-190 (1-{4-[4-(2-methoxyphenyl)-piperazin-1-yl]-butyl}-pyrrolidine-2,5-dione and isoindole-1,3-dione, respectively) were synthesized. The differences in their in vitro affinity for serotonin 5-HT7 and 5-HT1A receptors were explained using a conformational analysis. A bioactive conformation of those compounds for the 5-HT7 receptor, different from that established for 5-HT1A, was proposed. (C) 2004 Elsevier Ltd. All rights reserved.

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页码：5863 / 5866

页数：4

相关论文

共 20 条

[1] MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia:: blockade by drugs preventing 5-hydroxytryptamine depletion [J].

Aguirre, N ;

Ballaz, S ;

Lasheras, B ;

Del Rio, J .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1998, 346 (2-3) :181-188

[2]

BARD JA, 1993, J BIOL CHEM, V268, P23422

[3]

BOJARSKI AJ, 1993, PHARMAZIE, V48, P289

[4] SB-656104-A:: A novel 5-HT7 receptor antagonist with improved in vivo properties [J].

Forbes, IT ;

Douglas, S ;

Gribble, AD ;

Ife, RJ ;

Lightfoot, AP ;

Garner, AE ;

Riley, GJ ;

Jeffrey, P ;

Stevens, AJ ;

Stean, TO ;

Thomas, DR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (22) :3341-3344

[5] NAN-190 - AN ARYLPIPERAZINE ANALOG THAT ANTAGONIZES THE STIMULUS EFFECTS OF THE 5-HT1A AGONIST 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN (8-OH-DPAT) [J].

GLENNON, RA ;

NAIMAN, NA ;

PIERSON, ME ;

TITELER, M ;

LYON, RA ;

WEISBERG, E .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 154 (03) :339-341

[6] COSMO - A NEW APPROACH TO DIELECTRIC SCREENING IN SOLVENTS WITH EXPLICIT EXPRESSIONS FOR THE SCREENING ENERGY AND ITS GRADIENT [J].

KLAMT, A ;

SCHUURMANN, G .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, 1993, (05) :799-805

[7] Serotonin7 receptors (5-HT7Rs) and their ligands [J].

Leopoldo, A .

CURRENT MEDICINAL CHEMISTRY, 2004, 11 (05) :629-661

[8] Optimization of the pharmacophore model for 5-HT7R antagonism.: Design and synthesis of new naphtholactam and naphthosultam derivatives [J].

López-Rodríguez, ML ;

Porras, E ;

Morcillo, MJ ;

Benhamú, B ;

Soto, LJ ;

Lavandera, JL ;

Ramos, JA ;

Olivella, M ;

Campillo, M ;

Pardo, L .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (26) :5638-5650

[9] Synthesis and structure-activity relationships of a new model of arylpiperazines.: 4.: 1-[ω-(4-arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene)-2,5-pyrrolidinediones and -3-(9H-fluoren-9-ylidene)-2,5-pyrrolidinediones:: Study of the steric requirements of the terminal amide fragment on 5-HT1A affinity/selectivity [J].

López-Rodríguez, ML ;

Morcillo, MJ ;

Rovat, TK ;

Fernández, E ;

Vicente, B ;

Sanz, AM ;

Hernández, M ;

Orensanz, L .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (01) :36-49

[10] A novel, potent, and selective 5-HT7 antagonist:: (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970) [J].

Lovell, PJ ;

Bromidge, SM ;

Dabbs, S ;

Duckworth, DM ;

Forbes, IT ;

Jennings, AJ ;

King, FD ;

Middlemiss, DN ;

Rahman, SK ;

Saunders, DV ;

Collin, LL ;

Hagan, JJ ;

Riley, GJ ;

Thomas, DR .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (03) :342-345