STRUCTURE ACTIVITY RELATIONSHIP STUDIES OF CENTRAL-NERVOUS-SYSTEM AGENTS .5. EFFECT OF THE HYDROCARBON CHAIN ON THE AFFINITY OF 4-SUBSTITUTED 1-(3-CHLOROPHENYL)PIPERAZINES FOR 5-HT1A RECEPTOR-SITE

被引:50
作者
MOKROSZ, JL
PIETRASIEWICZ, M
DUSZYNSKA, B
CEGLA, MT
机构
[1] Institute of Pharmacology, Polish Academy of Sciences
关键词
D O I
10.1021/jm00091a004
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The effect of the hydrocarbon chain of the model 4-substituted 1-(3-chlorophenyl)piperazines 12-31 on their affinity for 5-HT1A receptor sites was investigated. It was found that elongation of the 4-n-alkyl chain strongly increases the 5-HT1A affinity of the investigated compounds. The affinity reaches the maximum (K(i) = 2.67 nM) for the n-hexyl derivative 20. It was shown that hydrophobic interactions of N-4 substituents of 1-arylpiperazines significantly contribute to their 5-HT1A affinity. The specific binding constant was defined as the receptor affinity of the protonated species of compounds under physiological conditions. The range of K(i)AH+ = 1-3 X 10(-11) M is a specific affinity limit of the investigated class of compounds at the 5-HT1A receptor sites.
引用
收藏
页码:2369 / 2374
页数:6
相关论文
共 37 条
  • [11] N-(PHTHALIMIDOALKYL) DERIVATIVES OF SEROTONERGIC AGENTS - A COMMON INTERACTION AT 5-HT1A SEROTONIN BINDING-SITES
    GLENNON, RA
    NAIMAN, NA
    PIERSON, ME
    SMITH, JD
    ISMAIEL, AM
    TITELER, M
    LYON, RA
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (08) : 1921 - 1926
  • [12] ARYLPIPERAZINE DERIVATIVES AS HIGH-AFFINITY 5-HT1A SEROTONIN LIGANDS
    GLENNON, RA
    NAIMAN, NA
    LYON, RA
    TITELER, M
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) : 1968 - 1971
  • [13] STERIC EFFECTS ON THE BASE STRENGTHS OF CYCLIC AMINES
    HALL, HK
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1957, 79 (20) : 5444 - 5447
  • [14] Hansch C., 1979, SUBSTITUENT CONSTANT
  • [15] STRUCTURAL DETERMINANTS OF 5-HT1A VERSUS 5-HT1D RECEPTOR-BINDING SITE SELECTIVITY
    HARRINGTON, MA
    SLEIGHT, AJ
    PITHA, J
    PEROUTKA, SJ
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 194 (01) : 83 - 90
  • [16] HIBERT M, 1987, BRAIN 5 HT1A RECEPTO, P27
  • [17] RADIOLIGAND BINDING STUDY OF A SERIES OF 5-HT1A RECEPTOR AGONISTS AND DEFINITION OF A STERIC MODEL OF THIS SITE
    HIBERT, MF
    MCDERMOTT, I
    MIDDLEMISS, DN
    MIR, AK
    FOZARD, JR
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1989, 24 (01) : 31 - 37
  • [18] GRAPHICS COMPUTER-AIDED RECEPTOR MAPPING AS A PREDICTIVE TOOL FOR DRUG DESIGN - DEVELOPMENT OF POTENT, SELECTIVE, AND STEREOSPECIFIC LIGANDS FOR THE 5-HT1A RECEPTOR
    HIBERT, MF
    GITTOS, MW
    MIDDLEMISS, DN
    MIR, AK
    FOZARD, JR
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (06) : 1087 - 1093
  • [19] BIOACTIVE CONFORMATION OF 1-ARYLPIPERAZINES AT CENTRAL SEROTONIN RECEPTORS
    HUFF, JR
    KING, SW
    SAARI, WS
    SPRINGER, JP
    MARTIN, GE
    WILLIAMS, M
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (07) : 945 - 948
  • [20] Kaliszan R., 1987, QUANTITATIVE STRUCTU