MY336-a

(1R*,3S*)-1,2,3,4-Tetrahydro-8-acetoxy-1,3-bis(acetoxymethyl)-2-acetyl-7 - methoxy-6-methyl-isoquinoline, C21H27NO8, Mr = 421.45, monoclinic, P2(1), a = 11.892 (2), b = 11.067 (2), c = 8.4866 (8) A, beta = 92.12 (1) degree, V = 1116.1 (5) A3, Z = 2, Dx = 1.255 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 7.702 cm-1, F(000) = 448, T = 293 K, R = 0.048, wR = 0.072 for 2178 observed reflections. The tetrahydropyridine ring adopts a half-boat conformation. The bond lengths and angles are within the normal ranges. There are no intermolecular contacts less than the sum of the van der Waals radii.

Streptomyces gabonae KY2234 was found to produce a new compound, MY336-a, which bound to beta-adrenergic receptor. The compound was isolated from the fermentation broth of KY2234. MY336-a showed a high affinity for the beta-receptor, labeled with [3H]dihydroalprenolol in the membrane fractions of rat heart (beta 1-adrenergic receptor) or lung (beta 2-adrenergic receptor), whereas the compound bound very weakly to alpha-adrenergic receptor, labeled with [3H]dihydroergokryptine in rat brain. the inhibition constants (Ki) of the compound were 0.73 and 0.14 microM for the beta-receptors of heart and lung, respectively. 5'-Guanylylimidodiphosphate (Gpp(NH)p) did not alter the affinity of the beta-receptors for MY336-a. In isolated guinea-pig atria, MY336-a produced an inhibition of the positive chronotropic and inotropic effects of isoproterenol. MY336-a also antagonized the relaxation of tone induced by isoproterenol in isolated guinea-pig trachea. No partial agonistic activity was detected in MY336-a in the isolated atria and trachea. In anaesthetized dogs, MY336-a (1 mg/kg, iv) exerted negative inotropic action (left ventricular dp/dt max, -32.6%).