Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors

Fabrizio Giordanetto; Laurent Knerr; Nidhal Selmi; Antonio Llinàs; Anders Lindqvist; Qing-Dong Wang; Pernilla Ståhlberg; Fredrik Thorstensson; Victoria Ullah; Kristina Nilsson; Gavin O'Mahony; Got Högberg; Emma Lindhardt; Annika Strand; Göran Duker

doi:10.1016/j.bmcl.2011.06.092

Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5557-61. doi: 10.1016/j.bmcl.2011.06.092. Epub 2011 Jun 30.

Authors

Fabrizio Giordanetto¹, Laurent Knerr, Nidhal Selmi, Antonio Llinàs, Anders Lindqvist, Qing-Dong Wang, Pernilla Ståhlberg, Fredrik Thorstensson, Victoria Ullah, Kristina Nilsson, Gavin O'Mahony, Got Högberg, Emma Lindhardt, Annika Strand, Göran Duker

Affiliation

¹ Medicinal Chemistry, AstraZeneca R&D CVGI iMed, Pepparedsleden 1, SE-431 83 Mölndal, Sweden. [email protected]

PMID: 21782423
DOI: 10.1016/j.bmcl.2011.06.092

Abstract

Chemical evolution of a HTS-based fragment hit resulted in the identification of N-(1-adamantyl)-2-[4-(2-tetrahydropyran-4-ylethyl)piperazin-1-yl]acetamide, a novel, selective T-type calcium channel (Ca(v)3.2) inhibitor with in vivo antihypertensive effect in rats.

MeSH terms

Acetamides / chemical synthesis
Acetamides / chemistry
Acetamides / pharmacology*
Animals
Antihypertensive Agents / chemical synthesis
Antihypertensive Agents / chemistry
Antihypertensive Agents / pharmacology*
Calcium Channels, T-Type / metabolism*
Dose-Response Relationship, Drug
Drug Discovery*
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
Ether-A-Go-Go Potassium Channels / metabolism
High-Throughput Screening Assays
Humans
Molecular Structure
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

Acetamides
Antihypertensive Agents
Cacna1h protein, rat
Calcium Channels, T-Type
Ether-A-Go-Go Potassium Channels