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

Research output: Contribution to journal › Article › 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 - 15 Jul 2018

Keywords

Benzothiazole
Cav2.2
Cav3.2
N-type calcium channel
Pain
T-type calcium channel

Access to Document

10.1016/j.bmc.2018.03.031Licence: In Copyright

Cite this

@article{9b956986fef749b99c48576ee6db27bc,

title = "Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels",

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.",

keywords = "Benzothiazole, Cav2.2, Cav3.2, N-type calcium channel, Pain, T-type calcium channel",

author = "Anjali Sairaman and Cardoso, {Fernanda Caldas} and Anjie Bispat and Lewis, {Richard J.} and Duggan, {Peter J.} and Tuck, {Kellie L.}",

year = "2018",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2018.03.031",

language = "English",

volume = "26",

pages = "3046--3059",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "11",

}

TY - JOUR

T1 - Synthesis and evaluation of aminobenzothiazoles as blockers of N- and T-type calcium channels

AU - Sairaman, Anjali

AU - Cardoso, Fernanda Caldas

AU - Bispat, Anjie

AU - Lewis, Richard J.

AU - Duggan, Peter J.

AU - Tuck, Kellie L.

PY - 2018/7/15

Y1 - 2018/7/15

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 - Cav2.2

KW - Cav3.2

KW - N-type calcium channel

KW - Pain

KW - T-type calcium channel

UR - http://www.scopus.com/inward/record.url?scp=85044772147&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/NHMRC/569927

UR - http://purl.org/au-research/grants/NHMRC/1019761

U2 - 10.1016/j.bmc.2018.03.031

DO - 10.1016/j.bmc.2018.03.031

M3 - Article

C2 - 29622412

AN - SCOPUS:85044772147

SN - 0968-0896

VL - 26

SP - 3046

EP - 3059

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 11

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this