The selectivity of α-adrenoceptor agonists for the human α1A, α1B, and α1D-adrenoceptors was written by Proudman, Richard G. W.;Baker, Jillian G.. And the article was included in Pharmacology Research & Perspectives in 2021.Formula: C10H17Cl2N3S This article mentions the following:
Highly selective drugs offer a way to minimize side-effects. For agonist ligands, this could be through highly selective affinity or highly selective efficacy, but this requires careful measurements of intrinsic efficacy. The α1-adrenoceptors are important clin. targets, and α1-agonists are used to manage hypotension, sedation, attention deficit hypersensitivity disorder (ADHD), and nasal decongestion. With 100 years of drug development, there are many structurally different compounds with which to study agonist selectivity. This study examined 62 α-agonists at the three human α1-adrenoceptor (α1A, α1B, and α1D) stably expressed in CHO cells. Affinity was measured using whole-cell 3H-prazosin binding, while functional responses were measured for calcium mobilization, ERK1/2-phosphorylation, and cAMP accumulation. Efficacy ratios were used to rank compounds in order of intrinsic efficacy. Adrenaline, noradrenaline, and phenylephrine were highly efficacious α1-agonists at all three receptor subtypes. A61603 was the most selective agonist and its very high α1A-selectivity was due to selective α1A-affinity (>660-fold). There was no evidence of Gq-calcium vs. ERK-phosphorylation biased signaling at theα1A, α1B, or α1D-adrenoceptors. There was little evidence for α1A calcium vs. cAMP biased signaling, although there were suggestions of calcium vs. cAMP bias the α1B-adrenoceptor. Comparisons of the rank order of ligand intrinsic efficacy suggest little evidence for selective intrinsic efficacy between the compounds, with perhaps the exception of dobutamine which may have some α1D-selective efficacy. There seems plenty of scope to develop affinity selective and intrinsic efficacy selective drugs for the α1-adrenoceptors in future. In the experiment, the researchers used many compounds, for example, 6-Allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (cas: 36085-73-1Formula: C10H17Cl2N3S).
6-Allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (cas: 36085-73-1) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Formula: C10H17Cl2N3S
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica