Hypocholesterolemic agent

Saponins. Although the hypocholesterolemic activity of saponins has been known since the 1950s, thek low potency and difficult purification sparked Htde interest in natural saponins as hypolipidemic agents. Synthetic steroids (292, 293) that are structurally related to saponins have been shown to lower plasma cholesterol in a variety of different species (252). Steroid (292) is designated CP-88,818 [99759-19-0]. The hypocholesterolemic agent CP-148,623 [150332-35-7] (293) is not absorbed into the systemic ckculation and does not inhibit enzymes involved in cholesterol synthesis, release, or uptake. Rather, (293) specifically inhibits cholesterol absorption into the intestinal mucosa (253). As of late 1996, CP-148,623 is in clinical trials as an agent that lowers blood concentrations of cholesterol (254). 

Therapeutic Function Hypocholesterolemic agent Chemical Name 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid Common Name —... 

QURESHi N, QURESHi A A (1992) Tocotrieuols novel hypocholesterolemic agents with antioxidant properties. In Vitamin E in Health and Disease. Eds Packer, L, Fuch, J, New York, Marcel Dekker 245-67. 

The clinical success of clofibrate has naturally led to the synthesis of numerous analogues intended for use as hypocholesterolemic agents. One of these, clofenpyride (84), is synthesized readily from p-< hlorophenoxy-2,2-dimethylacetic acid (83) by conversion to the acid chloride and reaction with 3-hydroxy-40... 

The synthesis of the decalin unit of compactin (59), a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which acts as an effective hypocholesterolemic agent, was planned to incorporate an intramolecular Diels-Alder reaction (Scheme 9.15) [57]. 

Pectin with 62% D.E. largely counteracted the increase in liver cholesterol levels brought about by dietary cholesterol. Low ester pectin (30% D.E.), polygalacturonic acid (PGA), and 50% esterified PGA were all without effect. Conflicting reports on the efficacy of pectin as a hypocholesterolemic agent may be due to variations in these parameters. For example, citrus pectin was found to be more effective than tomato pectin in lowering serum and hepatic cholesterol levels of rats (79). 

A Endo. Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiot 32 852-854, 1979. 

Title Substituted 2-Azetidinones Useful as Hypocholesterolemic Agents... 

The preparation of the Step 1 reagent and other hydroxy-substituted azetidinone derivatives useful as hypocholesterolemic agents is described by Rosenblum (1). 

Additional 2-azetidinone derivatives, (II), effective as hypocholesterolemic agents... 

A syndiesis of the hypocholesterolemic agent (+)-compactin centers around the Diels-Alder reaction of the chiral diene (282) with die chiral dienophile (281), which provided in a single operation die carbon framework of the target molecule (Scheme 67). However, facial and regiochemical selectivities of the additions were only moderate, giving rise to the formation of two legioisomers (283) and (284) the major product (283) was transformed into (+)-compactin. 

Probstfield JL, Lin TL, Peters J, Hunninghake DB. Carotenoids and vitamin A the effect of hypocholesterolemic agents on serum levels. Metabolism 1985 34(1) 88-91. 

Among more recent successes of this approach one can mention the discovery of lovastatin, also called mevino-lin (Figure 6.7), which was the basis of a new generation of hypocholesterolemic agents, acting by inhibition of HMG-CoA reductase. 

Endo, A., Monacolin, K. A new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme a reductase. J. Antibiot. 1980, 33, 334—336. 

Biosynthesis of the hypocholesterolemic agent, mevinolin by Aspergillus ter-reus, R.N. Moore, G. Bigam, J.K. Chan, A.M. Hogg, T.T. Nakashima and... 

Nutrition Dietary fiber Hypocholesterolemic agent Livestock and fish feed additive... 

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