5-Cyclic Amine-3-arylsulfonylindazoles as Novel 5-HT6 Receptor Antagonists

被引：20
|
作者：
Haydar, Simon N. [1 ]
Yun, Heedong [1 ]
Andrae, Patrick M. [1 ]
Mattes, James [1 ]
Zhang, Jean [2 ]
Kramer, Angela [2 ]
Smith, Deborah L. [2 ]
Huselton, Christine [3 ]
Graf, Radka [2 ]
Aschmies, Suzan [2 ]
Schechter, Lee E. [2 ]
Comery, Thomas A. [2 ]
Robichaud, Albert J. [1 ]
机构：
[1] Wyeth Ayerst Res, Chem Sci, Princeton, NJ 08543 USA
[2] Wyeth Ayerst Res, Discovery Neurosci, Princeton, NJ 08543 USA
[3] Wyeth Ayerst Res, Drug Safety & Metab, Collegeville, PA 19426 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 06期
关键词：
ACETYLCHOLINE-RELEASE; POTENT; DERIVATIVES; LOCALIZATION; DISCOVERY; SB-271046; HYDROGEN; LIGANDS; CORTEX;
D O I：
10.1021/jm901674f
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Novel 5-cyclic amine-3-arylsulfonylindazoles were prepared, and several analogues within this class have been identified as high-affinity 5-HT6 receptor ligands with improved pharmacokinetic and pharmacological properties. One selected example, 18b, showed good brain penetrability and a generally favorable pharmacokinetic profile with procognitive efficacy in the rat novel object recognition assay. The synthesis and structure activity relationship of this potent class are discussed.
引用
收藏
页码：2521 / 2527
页数：7
相关论文
共 50 条
  • [31] MEDI 40-Tetrahydro carbazoles: Novel, potent and selective 5-HT6 receptor antagonists
    Kambhampati, Rama Sastry
    Konda, Jagadish B.
    Kothmirkar, Prabhakar
    Bandyala, Trinath R.
    Yarra, Sivasekhar N. K.
    Arepalli, Sobhanadri
    Shinde, Anil K.
    Nirogi, Ramakrishna V. S.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2007, 234
  • [32] N1-(benzenesulfonyl)tryptamines as novel 5-HT6 antagonists
    Tsai, YC
    Dukat, M
    Slassi, A
    MacLean, N
    Demchyshyn, L
    Savage, JE
    Roth, BL
    Hufesein, S
    Lee, M
    Glennon, RA
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (20) : 2295 - 2299
  • [33] A three-dimensional pharmacophore model for 5-hydroxytryptamine6 (5-HT6) receptor antagonists
    López-Rodríguez, ML
    Benhamú, B
    de la Fuente, T
    Sanz, A
    Pardo, L
    Campillo, M
    JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (13) : 4216 - 4219
  • [34] The 5-HT6 receptor: memories are made of this
    Fone, KCF
    EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2005, 15 : S357 - S357
  • [35] PHARMACOKINETICS OF 5-HT6 RECEPTOR LIGANDS
    Mancinelli, Angelo
    PHARMACOLOGY OF 5-HT6 RECEPTORS, PT 1, 2010, 94 : 153 - 172
  • [36] THE 5-HT6 RECEPTOR AS A TARGET FOR DEVELOPING NOVEL ANTIOBESITY DRUGS
    Heal, David
    Gosden, Jane
    Smith, Sharon
    PHARMACOLOGY OF 5-HT6 RECEPTORS, PT II, 2011, 96 : 73 - 109
  • [37] MOLECULAR AND PHARMACOLOGICAL PROPERTIES OF A NOVEL SEROTONIN RECEPTOR (5-HT6)
    TRAIFFORT, E
    RUAT, M
    ARRANG, JM
    LEURS, R
    DIAZ, G
    TARDIVELLACOMBE, J
    SCHWARTZ, JC
    JOURNAL OF NEUROCHEMISTRY, 1993, 61 : S89 - S89
  • [38] Promising novel 5-HT6 receptor ligands to treat obesity
    Pauwels, P. J.
    Fisas, A.
    Codony, X.
    Buschmann, H.
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2006, 101 : 16 - 16
  • [39] Tetrahydrocarbazole derivatives as novel and selective 5-HT6 receptor ligands
    Konda, Jagadishbabu
    Kambhampati, Ramasastry
    Kothmirkar, Prabhakar
    Arepalli, Sobhanadri
    Bandyala, Trinath Reddy
    Gudla, Parandhama
    Shinde, Anil K.
    Nirogi, Ramakrishna
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
  • [40] An assessment of the effects of serotonin 6 (5-HT6) receptor antagonists in rodent models of learning
    Lindner, MD
    Hodges, DB
    Hogan, JB
    Orie, AF
    Corsa, JA
    Barten, DM
    Polson, C
    Robertson, BJ
    Guss, VL
    Gillman, KW
    Starrett, JE
    Gribkoff, VK
    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 307 (02): : 682 - 691
12345