SB-656104-A:: A novel 5-HT7 receptor antagonist with improved in vivo properties

被引：67

作者：

Forbes, IT ^{[1
]}

Douglas, S ^{[1
]}

Gribble, AD ^{[1
]}

Ife, RJ ^{[1
]}

Lightfoot, AP ^{[1
]}

Garner, AE ^{[1
]}

Riley, GJ ^{[1
]}

Jeffrey, P ^{[1
]}

Stevens, AJ ^{[1
]}

Stean, TO ^{[1
]}

Thomas, DR ^{[1
]}

机构：

[1] GlaxoSmithKline, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 22期

关键词：

D O I：

10.1016/S0960-894X(02)00690-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A focused SAR study around the previously reported selective 5-HT7 receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：3341 / 3344

页数：4

共 13 条

[1] BARD JA, 1993, J BIOL CHEM, V268, P23422
[2] Batcho A. D., 1985, ORG SYNTH, V63, P214, DOI DOI 10.15227/0RGSYN.063.0214
[3] FORBES II, UNPUB
[4] *GLAX, UNPUB
[5] GUSCOTT M, 2000, SOC NEUR SAT M SER N
[6] Characterization of SB-269970-A, a selective 5-HT7 receptor antagonist
Hagan, JJ
Price, GW
Jeffrey, P
Deeks, NJ
Stean, T
Piper, D
Smith, MI
Upton, N
Medhurst, AD
Middlemiss, DN
Riley, GJ
Lovell, PJ
Bromidge, SM
Thomas, DR
[J]. BRITISH JOURNAL OF PHARMACOLOGY, 2000, 130 (03) : 539 - 548
[7] Molecular, pharmacological and functional diversity of 5-HT receptors
Hoyer, D
Hannon, JP
Martin, GR
[J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2002, 71 (04) : 533 - 554
[8] A novel, potent, and selective 5-HT7 antagonist:: (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970)
Lovell, PJ
Bromidge, SM
Dabbs, S
Duckworth, DM
Forbes, IT
Jennings, AJ
King, FD
Middlemiss, DN
Rahman, SK
Saunders, DV
Collin, LL
Hagan, JJ
Riley, GJ
Thomas, DR
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (03) : 342 - 345
[9] A NOVEL ADENYLYL CYCLASE-ACTIVATING SEROTONIN RECEPTOR (5-HT7) IMPLICATED IN THE REGULATION OF MAMMALIAN CIRCADIAN-RHYTHMS
LOVENBERG, TW
BARON, BM
DELECEA, L
MILLER, JD
PROSSER, RA
REA, MA
FOYE, PE
RACKE, M
SLONE, AL
SIEGEL, BW
DANIELSON, PE
SUTCLIFFE, JG
ERLANDER, MG
[J]. NEURON, 1993, 11 (03) : 449 - 458
[10] MOLECULAR-CLONING, CHARACTERIZATION, AND LOCALIZATION OF A HIGH-AFFINITY SEROTONIN RECEPTOR (5-HT(7)) ACTIVATING CAMP FORMATION
RUAT, M
TRAIFFORT, E
LEURS, R
TARDIVELLACOMBE, J
DIAZ, J
ARRANG, JM
SCHWARTZ, JC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (18) : 8547 - 8551

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