Conformational flexibility of serotonin(1A) receptor ligands from crystallographic data. Updated model of the receptor pharmacophore

被引：40

作者：

Chilmonczyk, Z

SzelejewskaWozniakowska, A

Cybulski, J

Cybulski, M

Koziol, AE

Gdaniec, M

机构：

[1] PHARMACEUT RES INST,PL-00793 WARSAW,POLAND

[2] MARIE CURIE SKLODOWSKA UNIV,FAC CHEM,PL-20031 LUBLIN,POLAND

[3] ADAM MICKIEWICZ UNIV POZNAN,FAC CHEM,PL-60780 POZNAN,POLAND

来源：

ARCHIV DER PHARMAZIE | 1997年 / 330卷 / 05期

关键词：

anxiety; serotonin receptors; crystal structure; conformational analysis;

D O I：

10.1002/ardp.19973300507

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Preparation and affinity to 5-HT1A and 5-HT2A receptors of new buspirone analogues 7-17 are reported. The compounds possess high to low affinity to 5-HT1A and moderate to low to 5-HT2A receptors. The crystal structures have been determined for compounds 11, 12, 13, and 14. For low affinity ligand (15) of 5-HT1A receptor conformational analysis was performed and compared with similar analyses performed for know high (buspirone 1) and very high (WY-48,723 2) affinity ligands of the receptor. Structure-activity relationship is discussed for the affinity to 5-HT1A receptor. A three-point pharmocophore explaining interactions of buspirone-like molecules with the receptor binding site is proposed.

引用

页码：146 / 160

页数：15

共 45 条

[1]

Barrett J.E., 1991, 5 HT1A AGONISTS 5 HT, P59

[2] ANTICONFLICT AND DISCRIMINATIVE STIMULUS EFFECTS OF THE 5-HT1A COMPOUNDS WY-47,846 AND WY-48,723 AND THE MIXED 5-HT1A AGONIST 5-HT2 ANTAGONIST WY-50,324 IN PIGEONS [J].

BARRETT, JE ;

ZHANG, L .

DRUG DEVELOPMENT RESEARCH, 1991, 24 (02) :179-188

[3]

BOJARSKI AJ, 1993, PHARMAZIE, V48, P289

[4]

Brocco M.J., 1990, Behav Pharmacol, V1, P403

[5] BUSPIRONE ANALOGS AS LIGANDS OF THE 5-HT1A RECEPTOR .1. THE MOLECULAR-STRUCTURE OF BUSPIRONE AND ITS 2 ANALOGS [J].

CHILMONCZYK, Z ;

LES, A ;

WOZNIAKOWSKA, A ;

CYBULSKI, J ;

KOZIOL, AE ;

GDANIEC, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (10) :1701-1710

[6]

CUELEMANS DLS, 1985, PHARMACOPSYCHIATRY, V18, P303

[7] AN EFFICIENT SYNTHESIS OF BUSPIRONE AND ITS ANALOGS [J].

CYBULSKI, J ;

CHILMONCZYK, Z ;

SZELEJEWSKI, W ;

WOJTASIEWICZ, K ;

WROBEL, JT .

ARCHIV DER PHARMAZIE, 1992, 325 (05) :313-315

[8]

CYBULSKI J, 1996, J MOL STRUCT, V385, P195

[9]

DEAKIN JFW, 1988, PHARM BIOCH BEHAV, V29, P19

[10]

Diels O, 1928, LIEBIGS ANN CHEM, V460, P98

← 1 2 3 4 5 →