Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

Anjali Sairaman; Fernanda Caldas Cardoso; Anjie Bispat; Richard J. Lewis; Peter J. Duggan; Kellie L. Tuck

doi:10.1016/j.bmc.2018.03.031

Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

Anjali Sairaman, Fernanda Caldas Cardoso, Anjie Bispat, Richard J. Lewis, Peter J. Duggan, Kellie L. Tuck

School of Chemistry

Research output: Contribution to journal › Article › Research › peer-review

11 Citations (Scopus)

Abstract

Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both Ca_V2.2 and Ca_V3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of Ca_V2.2 and Ca_V3.2 channels.

Original language	English
Pages (from-to)	3046-3059
Number of pages	14
Journal	Bioorganic & Medicinal Chemistry
Volume	26
Issue number	11
DOIs	https://doi.org/10.1016/j.bmc.2018.03.031
Publication status	Published - 2018

Keywords

Benzothiazole
Ca2.2
Ca3.2
N-type calcium channel
Pain
T-type calcium channel

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10.1016/j.bmc.2018.03.031

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abstract = "Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both CaV2.2 and CaV3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of CaV2.2 and CaV3.2 channels.",

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AU - Sairaman, Anjali

AU - Cardoso, Fernanda Caldas

AU - Bispat, Anjie

AU - Lewis, Richard J.

AU - Duggan, Peter J.

AU - Tuck, Kellie L.

PY - 2018

Y1 - 2018

N2 - Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both CaV2.2 and CaV3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of CaV2.2 and CaV3.2 channels.

AB - Both N- and T-type calcium ion channels have been implicated in pain transmission and the N-type channel is a well-validated target for the treatment of neuropathic pain. An SAR investigation of a series of substituted aminobenzothiazoles identified a subset of five compounds with comparable activity to the positive control Z160 in a FLIPR-based intracellular calcium response assay measuring potency at both CaV2.2 and CaV3.2 channels. These compounds may form the basis for the development of drug leads and tool compounds for assessing in vivo effects of variable modulation of CaV2.2 and CaV3.2 channels.

KW - Benzothiazole

KW - Ca2.2

KW - Ca3.2

KW - N-type calcium channel

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KW - T-type calcium channel

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JO - Bioorganic & Medicinal Chemistry

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ER -

Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

Abstract

Keywords

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