PYRIMIDO[5,4-B]INDOLE DERIVATIVES .1. A NEW CLASS OF POTENT AND SELECTIVE ALPHA-1 ADRENOCEPTOR LIGANDS

被引：67
|
作者：
RUSSO, F [1 ]
ROMEO, G [1 ]
GUCCIONE, S [1 ]
DEBLASI, A [1 ]
机构：
[1] IST RIC FARMACOL MARIO NEGRI, CONSORZIO MARIO NEGRI SUD, I-66030 SANTA MARIA IMBARO, ITALY
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 06期
关键词：
D O I：
10.1021/jm00110a014
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A number of 3-substituted pyrimido[5,4-b]indole-2,4-diones (7-23) were evaluated for their in vitro alpha-1 adrenoceptor affinity by radioligand receptor binding assays. Some compounds bearing a (phenylpiperazinyl)alkyl side chain were potent alpha-1 adrenoceptor ligands. The most active derivative in displacement of [H-3]prazosin from rat cortical membranes was 3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b]indole-2,4-dione (10) (K(i) = 0.21 nM). Discrete modifications in the structure resulted in higher selectivity (> 10 000 times) for alpha-1 than alpha-2, beta-2, and 5HT1A receptors. Some compounds also had affinity for the 5HT1A receptor. The most selective alpha-1 ligand was 3-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b]indole-2,4-dione (13).
引用
收藏
页码：1850 / 1854
页数：5
相关论文
共 50 条
  • [41] STUDIES ON SYNTHESES OF SULFUR-CONTAINING PYRIMIDO[5,4-D]PYRIMIDINE DERIVATIVES .1. SYNTHESES OF PYRIMIDO[5,4-D]PYRIMIDINE DERIVATIVES POSSESSING METHYLSULFONYL OR SULFONAMIDE GROUP AT 2-POSITION
    IMAI, K
    ISHIDA, T
    HORIGUCHI, H
    OZASA, T
    OHONO, M
    KAWAHARA, S
    MURAKAMI, M
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 1976, 96 (05): : 578 - 585
  • [42] STUDY OF NITROGENIC AND SULFURIC HETEROCYCLES .24. SYNTHESIS OF PYRIMIDO[5,4-B][1,4]OXAZINONES-7
    SAZONOV, NV
    SAFONOVA, TS
    KHIMIYA GETEROTSIKLICHESKIKH SOEDINENII, 1972, (09): : 1285 - &
  • [43] Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists
    Fang, Yuanying
    Zhang, Shaokun
    Li, Min
    Xiong, Lijuan
    Tu, Liangxing
    Xie, Saisai
    Jin, Yi
    Liu, Yanhua
    Yang, Zunhua
    Liu, Ronghua
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2020, 35 (01) : 50 - 58
  • [44] Discovery, optimization and evaluation of isothiazolo[5,4-b]pyridine derivatives as RIPK1 inhibitors with potent in vivo anti-SIRS activity
    Hao, Yongjin
    Yang, Chengkui
    Shu, Chang
    Li, Zhanhui
    Xia, Kaijiang
    Wu, Shuwei
    Ma, Haikuo
    Tian, Sheng
    Ji, Yuting
    Li, Jingjing
    He, Sudan
    Zhang, Xiaohu
    BIOORGANIC CHEMISTRY, 2022, 129
  • [45] STUDY OF NITROGEN AND SULFUR HETEROCYCLES .26. PROPERTIES OF PYRIMIDO[5,4-B][1,4]-OXAZINONES-7
    SAZONOV, NV
    SAFONOVA, TS
    KHIMIYA GETEROTSIKLICHESKIKH SOEDINENII, 1973, (02): : 171 - 174
  • [46] New benzocycloalkylpiperazines, potent and selective 5-HT1A receptor ligands
    ElAhmad, Y
    Laurent, E
    Maillet, P
    Talab, A
    Teste, JF
    Dokhan, R
    Tran, G
    Ollivier, R
    JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (06) : 952 - 960
  • [47] Design, synthesis, and SAR of thiazolo[5,4-b]pyridine derivatives as novel SIRT1 activators
    Vu, Chi B.
    Ng, Pui Yee
    Disch, Jeremy S.
    Oalmann, Christopher
    Bemis, Jean E.
    Nunes, Joseph J.
    Milne, Jill C.
    Carney, David P.
    Lynch, Amy V.
    Smith, Jesse J.
    Lambert, Philip D.
    Gagne, David J.
    Cote, Angela
    Davis, Meghan
    Lainez, Elden
    Jirousek, Michael R.
    Perni, Robert B.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
  • [48] STUDIES ON QUINAZOLINES .5. 2,3-DIHYDROIMIDAZO[1,2-C]QUINAZOLINE DERIVATIVES - A NOVEL CLASS OF POTENT AND SELECTIVE ALPHA(1)-ADRENOCEPTOR ANTAGONISTS AND ANTIHYPERTENSIVE AGENTS
    CHERN, JW
    TAO, PL
    YEN, MH
    LU, GY
    SHIAU, CY
    LAI, YJ
    CHIEN, SL
    CHAN, CH
    JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (15) : 2196 - 2207
  • [49] SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF 6H-THIAZOLO [3',2'-1,2]-5-OXOPYRIMIDO[5,4-B]INDOLE DERIVATIVES, A NEW HETEROCYCLIC RING-SYSTEM
    RUSSO, F
    ROMEO, G
    GUCCIONE, S
    BOUSQUET, E
    CARUSO, A
    LEONE, MG
    ATTAGUILE, G
    AMICOROXAS, M
    PHARMAZIE, 1990, 45 (04): : 242 - 244
  • [50] SYNTHESIS AND CARDIOTONIC ACTIVITY OF PYRIMIDO[5,4-B][1,4]OXAZINONES AND 1,4-DIOXINO[2,3-D]PYRIMIDINES
    MATYUS, P
    MAKK, N
    TEGDES, A
    KOSARY, J
    KASZTREINER, E
    PODANYI, B
    RABLOCZKY, G
    KURTHY, M
    JOURNAL OF HETEROCYCLIC CHEMISTRY, 1990, 27 (02) : 151 - 155
12345