Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists

Alan J Henderson, Peter R Guzzo, Animesh Ghosh, Jagjit Kaur, Jia-Man Koo, Kassoum Nacro, Shailaja Panduga, Rashmi Pathak, Bharat Shimpukade, Valentina Tan, Kai Xiang, Jonathan D Wierschke, Matthew L Isherwood

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Resumé

A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography.
OriginalsprogEngelsk
TidsskriftBioorganic & Medicinal Chemistry Letters
Vol/bind22
Udgave nummer4
Sider (fra-til)1494-8
Antal sider5
ISSN0960-894X
DOI
StatusUdgivet - 2012

Fingeraftryk

Pharmacokinetics
Pharmacodynamics
Indoles
Serotonin Antagonists
Serotonin
serotonin 6 receptor
indole
Autoradiography
In Vitro Techniques

Citer dette

Henderson, A. J., Guzzo, P. R., Ghosh, A., Kaur, J., Koo, J-M., Nacro, K., ... Isherwood, M. L. (2012). Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists. Bioorganic & Medicinal Chemistry Letters, 22(4), 1494-8. https://doi.org/10.1016/j.bmcl.2012.01.022
Henderson, Alan J ; Guzzo, Peter R ; Ghosh, Animesh ; Kaur, Jagjit ; Koo, Jia-Man ; Nacro, Kassoum ; Panduga, Shailaja ; Pathak, Rashmi ; Shimpukade, Bharat ; Tan, Valentina ; Xiang, Kai ; Wierschke, Jonathan D ; Isherwood, Matthew L. / Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists. I: Bioorganic & Medicinal Chemistry Letters. 2012 ; Bind 22, Nr. 4. s. 1494-8.
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abstract = "A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography.",
keywords = "Administration, Oral, Animals, Caco-2 Cells, Humans, Indoles, Molecular Structure, Protein Binding, Purinergic P1 Receptor Antagonists, Rats, Rats, Sprague-Dawley, Receptors, Serotonin, Serotonin Antagonists, Structure-Activity Relationship",
author = "Henderson, {Alan J} and Guzzo, {Peter R} and Animesh Ghosh and Jagjit Kaur and Jia-Man Koo and Kassoum Nacro and Shailaja Panduga and Rashmi Pathak and Bharat Shimpukade and Valentina Tan and Kai Xiang and Wierschke, {Jonathan D} and Isherwood, {Matthew L}",
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year = "2012",
doi = "10.1016/j.bmcl.2012.01.022",
language = "English",
volume = "22",
pages = "1494--8",
journal = "Bioorganic & Medicinal Chemistry Letters",
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Henderson, AJ, Guzzo, PR, Ghosh, A, Kaur, J, Koo, J-M, Nacro, K, Panduga, S, Pathak, R, Shimpukade, B, Tan, V, Xiang, K, Wierschke, JD & Isherwood, ML 2012, 'Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists', Bioorganic & Medicinal Chemistry Letters, bind 22, nr. 4, s. 1494-8. https://doi.org/10.1016/j.bmcl.2012.01.022

Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists. / Henderson, Alan J; Guzzo, Peter R; Ghosh, Animesh; Kaur, Jagjit; Koo, Jia-Man; Nacro, Kassoum; Panduga, Shailaja; Pathak, Rashmi; Shimpukade, Bharat; Tan, Valentina; Xiang, Kai; Wierschke, Jonathan D; Isherwood, Matthew L.

I: Bioorganic & Medicinal Chemistry Letters, Bind 22, Nr. 4, 2012, s. 1494-8.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists

AU - Henderson, Alan J

AU - Guzzo, Peter R

AU - Ghosh, Animesh

AU - Kaur, Jagjit

AU - Koo, Jia-Man

AU - Nacro, Kassoum

AU - Panduga, Shailaja

AU - Pathak, Rashmi

AU - Shimpukade, Bharat

AU - Tan, Valentina

AU - Xiang, Kai

AU - Wierschke, Jonathan D

AU - Isherwood, Matthew L

N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.

PY - 2012

Y1 - 2012

N2 - A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography.

AB - A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography.

KW - Administration, Oral

KW - Animals

KW - Caco-2 Cells

KW - Humans

KW - Indoles

KW - Molecular Structure

KW - Protein Binding

KW - Purinergic P1 Receptor Antagonists

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Serotonin

KW - Serotonin Antagonists

KW - Structure-Activity Relationship

U2 - 10.1016/j.bmcl.2012.01.022

DO - 10.1016/j.bmcl.2012.01.022

M3 - Journal article

VL - 22

SP - 1494

EP - 1498

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 4

ER -