Identification of fused bicyclic heterocycles as potent and selective 5-HT2A receptor antagonists for the treatment of insomnia

被引：9

作者：

Xiong, Yifeng ^{[1
]}

Ullman, Brett ^{[1
]}

Choi, Jin-Sun Karoline ^{[1
]}

Cherrier, Martin ^{[2
]}

Strah-Pleynet, Sonja ^{[1
]}

Decaire, Marc ^{[1
]}

Feichtinger, Konrad ^{[1
]}

Frazer, John M. ^{[1
]}

Yoon, Woo H. ^{[1
]}

Whelan, Kevin ^{[1
]}

Sanabria, Erin K. ^{[1
]}

Grottick, Andrew J. ^{[1
]}

Al-Shamma, Hussien ^{[1
]}

Semple, Graeme ^{[1
]}

机构：

[1] Arena Pharmaceut Inc, San Diego, CA 92121 USA

[2] Biotage, Charlottesville, VA 22911 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 05期

关键词：

Serotonin; 5-HT2A antagonist; Nelotanserin; Insomnia; SLEEP;

D O I：

10.1016/j.bmcl.2012.01.080

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of fused bicyclic heterocycles was identified as potent and selective 5-HT2A receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation. (c) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1870 / 1873

页数：4

共 50 条

[1] Role of 5-HT2A receptor antagonists in the treatment of insomnia
Vanover, Kimberly E.
Davis, Robert E.
[J]. NATURE AND SCIENCE OF SLEEP, 2010, 2 : 139 - 150
[2] 2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists
Shireman, Brock T.
Dvorak, Curt A.
Rudolph, Dale A.
Bonaventure, Pascal
Nepomuceno, Diane
Dvorak, Lisa
Miller, Kirsten L.
Lovenberg, Timothy W.
Carruthers, Nicholas I.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (06) : 2103 - 2108
[3] "Selective" serotonin 5-HT2A receptor antagonists
Casey, Austen B.
Cui, Meng
Booth, Raymond G.
Canal, Clinton E.
[J]. BIOCHEMICAL PHARMACOLOGY, 2022, 200
[4] Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists
Bromidge, SM
Clarke, SE
King, FD
Lovell, PJ
Newman, H
Riley, G
Routledge, C
Serafinowska, HT
Smith, DR
Thomas, DR
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (10) : 1357 - 1360
[5] SEROTONIN 5-HT2A RECEPTOR ANTAGONISTS IN THE TREATMENT OF INSOMNIA: PRESENT STATUS AND FUTURE PROSPECTS
Monti, J. M.
[J]. DRUGS OF TODAY, 2010, 46 (03) : 183 - 193
[6] SEROTONIN 5-HT2A RECEPTOR ANTAGONISTS FOR TREATMENT OF SCHIZOPHRENIA
Ebdrup, Bjorn H.
Rasmussen, Hans
Arnt, Jorn
Glenthoj, Birte
[J]. SCHIZOPHRENIA RESEARCH, 2012, 136 : S264 - S265
[7] Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics
Lee, T
Robichaud, AJ
Boyle, KE
Lu, YM
Robertson, DW
Miller, KJ
Fitzgerald, LW
McElroy, JF
Largent, BL
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (04) : 767 - 770
[8] 4-fluorosulfonylpiperidines:: Selective 5-HT2A ligands for the treatment of insomnia
Fish, LR
Gilligan, MT
Humphries, AC
Ivarsson, M
Ladduwahetty, T
Merchant, KJ
O'Connor, D
Patel, S
Philipps, E
Vargas, HM
Hutson, PH
MacLeod, AM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (16) : 3665 - 3669
[9] 2-alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists (vol 18, pg 2103, 2008)
Shireman, Brock T.
Dvorak, Curt A.
Rudolph, Dale A.
Bonaventure, Pascal
Nepomuceno, Diane
Dvorak, Lisa
Miller, Kirsten L.
Lovenberg, Timothy W.
Carruthers, Nicholas I.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (14) : 4253 - 4253
[10] Potent and selective 5-HT6 receptor antagonists
Bromidge, SM
[J]. MEDICINAL CHEMISTRY INTO THE MILLENNIUM, 2001, (264): : 101 - 119

← 1 2 3 4 5 →