ChemInform Abstract: Synthesis and Biological Evaluation of 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent and Selective M2 Muscarinic Receptor Antagonists

Autor:	Tadao Shibanuma, Toshihiro Watanabe, Kenji Takizawa, Seiko Hirano, Isao Kinoyama
Rok vydání:	2010
Předmět:	chemistry.chemical_classification Stereochemistry General Medicine Submandibular gland Affinities chemistry.chemical_compound medicine.anatomical_structure chemistry In vivo Muscarinic acetylcholine receptor medicine Piperidine Antagonism Linker Alkyl
Zdroj:	ChemInform. 30
ISSN:	1522-2667 0931-7597
DOI:	10.1002/chin.199945193
Popis:	A series of 1, 2, 3, 4-tetrahydroisoquinoline derivatives containing the 5, 11-dihydro-6H-pyrido[2, 3-b][1, 4]benzodiazepin-6-one skeleton were prepared and evaluated for their in vitro binding affinities to muscarinic receptors and for antagonism of bradycardia in vivo. Among them, compound 3f had the highest affinity for M2 muscarinic receptors in the heart (pKi=9.1) with low affinity for M3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the benzene ring fused piperidine and the alkyl linker chain lenght are crucially important for increased M2 affinity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::9f942bb487057ee73ffd3e4f43d1c750 https://doi.org/10.1002/chin.199945193 Zobrazit plný text záznamu Plný text