Phenethylamine inhibitors of partially purified rat and human pancreatic lipase.
Methodology for the preparation of rat and human pancreatic lipase (EC 3.1.1.3) is described, which resulted in good yield of partially purified, stable enzyme useful for kinetic studies. Apparent Km values for the rat (6.5 mM) and human (3.5 mM) enzyme were determined with triolein as the substrate. Several compounds of the phenethylamine class were found to be inhibitors of both rat and human pancreatic lipase. The structural feature in the phenethylamine series tested, which appeared to be necessary for lipase inhibition, was a halogenated substituent on the 3 or 4 position of the aromatic ring as in flutiorex, fenfluramine, N-benzyl-beta-methoxy-3-(trifluoromethyl)phenethylamine (I), chlorphentermine and p-chloroamphetamine. A chloro group at the 2 position was ineffective (chlortermine). Alterations in the ethylamine portion of the molecule did not cause significant changes in the inhibitory properties of the active phenethylamines.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D066298:In Vitro Techniques; D008049:Lipase / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000201:enzymology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D010627:Phenethylamines; D008049:Lipase