Synthesis and Biological Activity of 2-Aminothiazolines and 2-Mercaptothiazolines as Octopaminergic Agonists

抄録

2-Aminothiazoline derivatives were synthesized by both hydrochloric acid-catalyzed cyclization of thiourea and by cyclization of β-aminoalkyl hydrogen sulfate with isothiocyanate in the presence of sodium hydroxide. Substituted 2-mercaptothiazoline derivatives were prepared by alkylation or acylation of the sodium salt of 2-mercaptothiazoline, which was obtained from β-aminoalkyl hydrogen sulfate with carbon disulfide. 2-(4-Chloro-0-toluidino)-2-thiazoline (111-16) was 33% as effective as octopamine at 100μM in stimulating adenylate cyclase of Penplaneta amencana ventral-nerve-cord homogenates. Its activity was nonadditive to the activity of octopamine. Stimulation of nerve-cord adenylate-cyclase activity by III-16 was inhibited by several antagonists, including mianserin, cyproheptadine, ehlorpromazine and gramine. The rank-order ability of these antagonists to block the activation by III-16 was identical to the rank-order ability of the same antagonists to block enzyme activation by octopamine. The β-adrenergic antagonist propranolol was less potent. These data suggest that 111-16 is a potent and selective agonist of octopamine-activated adenylate cyclase. Aminothiazolines which activated adenylate cyclase by 10-87% relative to octopamine also had acaricidal activity at 300 ppm, indicating a correlation between the in vitro octopaminergic-agonist activity and in vivo acaricidal activity of aminothiazolines.