Synthesis and beta-adrenoceptor activity of the erythro and threo isomers of substituted alpha-hydroxytrimetoquinol.
The synthesis and pharmacological activity of erythro and threo isomers of 1-(3',4',5'-trimethoxy-alpha-hydroxy-benzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, 2 and 3, are reported. The structural assignments of 2 and 3 are based upon NMR spectra of the 6,7-dibenzyl precursors, 6 and 10, and of the synthetic derivatives of 13alpha- and 13beta-hydroxy-2,3-(dibenzyloxy)-9,10,11-trimethoxytetrahydroprotoberberine, 8 and 12, respectively. The erythro isomer 2 was a more potent beta-adrenoceptor stimulant than the threo isomer 3 in guinea pig atrial, guinea pig tracheal, and rat adipocyte preparations. The differential activity of these compounds on lipolysis was favorably correlated to changes in the stimulation of adenylate cyclase activity and cAMP accumulation in rat adipocytes.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000138:chemical synthesis*; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D013237:Stereoisomerism; D014213:Tretoquinol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D007546:Isoquinolines; D000242:Cyclic AMP; D014213:Tretoquinol