2,4-disubstituted pyrroles:: Synthesis, traceless linking and pharmacological investigations leading to the dopamine D4 receptor partial agonist FAUC 356

被引：26

作者：

Bergauer, M ^{[1
]}

Hübner, H ^{[1
]}

Gmeiner, P ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Emil Fischer Ctr, Dept Med Chem, D-91052 Erlangen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(02)00316-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Solution-phase synthesis and a solid-phase supported approach to piperazinylmethyl substituted pyrroles are described. Receptor binding studies and the measurement of D4 ligand efficacy led to the ethynylpyrrole 1d (FAUC 356) exerting selective D4 binding and substantial ligand efficacy (66%, EC50 = 1.9 nM). This activity profile might be of interest for the treatment of ADHD. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1937 / 1940

页数：4

共 26 条

[1] MODULATION OF INTRACELLULAR CYCLIC-AMP LEVELS BY DIFFERENT HUMAN DOPAMINE D4 RECEPTOR VARIANTS
ASGHARI, V
SANYAL, S
BUCHWALDT, S
PATERSON, A
JOVANOVIC, V
VANTOL, HHM
[J]. JOURNAL OF NEUROCHEMISTRY, 1995, 65 (03) : 1157 - 1165
[2] Bergauer M, 2002, SYNTHESIS-STUTTGART, P274
[3] Bergauer M, 2001, SYNTHESIS-STUTTGART, P2281
[4] CHIO CL, 1994, MOL PHARMACOL, V45, P51
[5] Benzamide bioisosteres incorporating dihydroheteroazole substructures:: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179)
Einsiedel, J
Hübner, H
Gmeiner, P
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (18) : 2533 - 2536
[6] NGD 94-1 as an agonist at human recombinant dopamine D4.4 receptors expressed in HEK293 cells
Gazi, L
Sommer, B
Nozulak, J
Schoeffter, P
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 372 (03) : R9 - R10
[7] 2,2-Dicyanovinyl as a nonaromatic aryl bioisostere:: Synthesis, binding experiments and SAR studies of highly selective dopamine D4 receptor ligands
Haubmann, C
Hübner, H
Gmeiner, P
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (14) : 1969 - 1972
[8] STRUCTURAL SUBTYPES OF THE DOPAMINE D2 RECEPTOR ARE FUNCTIONALLY DISTINCT - EXPRESSION OF THE CLONED D2A AND D2B SUBTYPES IN A HETEROLOGOUS CELL-LINE
HAYES, G
BIDEN, TJ
SELBIE, LA
SHINE, J
[J]. MOLECULAR ENDOCRINOLOGY, 1992, 6 (06) : 920 - 926
[9] The dopamine D4 receptor:: a controversial therapeutic target
Hrib, NJ
[J]. DRUGS OF THE FUTURE, 2000, 25 (06) : 587 - 611
[10] Cyanoindole derivatives as highly selective dopamine D4 receptor partial agonists:: Solid-phase synthesis, binding assays, and functional experiments
Hübner, H
Kraxner, J
Gmeiner, P
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (23) : 4563 - 4569

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