title: Discovery of N-(1-adamantyl)-2-(4-alkylpiperazin-1-yl)acetamide derivatives as T-type calcium channel (Cav3.2) inhibitors.
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.
authors.affiliation: Medicinal Chemistry, AstraZeneca R&D CVGI iMed, Pepparedsleden 1, SE-431 83 Mölndal, Sweden. fabrizio.giordanetto@astrazeneca.com
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giordanetto
authors.forename: Laurent
authors.initials: L
authors.lastname: Knerr
authors.forename: Nidhal
authors.initials: N
authors.lastname: Selmi
authors.forename: Antonio
authors.initials: A
authors.lastname: Llinàs
authors.forename: Anders
authors.initials: A
authors.lastname: Lindqvist
authors.forename: Qing-Dong
authors.initials: QD
authors.lastname: Wang
authors.forename: Pernilla
authors.initials: P
authors.lastname: Ståhlberg
authors.forename: Fredrik
authors.initials: F
authors.lastname: Thorstensson
authors.forename: Victoria
authors.initials: V
authors.lastname: Ullah
authors.forename: Kristina
authors.initials: K
authors.lastname: Nilsson
authors.forename: Gavin
authors.initials: G
authors.lastname: O'Mahony
authors.forename: Got
authors.initials: G
authors.lastname: Högberg
authors.forename: Emma
authors.initials: E
authors.lastname: Lindhardt
authors.forename: Annika
authors.initials: A
authors.lastname: Strand
authors.forename: Göran
authors.initials: G
authors.lastname: Duker
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000959:Antihypertensive Agents; C509958:Cacna1h protein, rat; D020747:Calcium Channels, T-Type; D051638:Ether-A-Go-Go Potassium Channels