Lipases inhibitors

Roche carries out asymmetric hydrogenation of a p-keto-ester for a pancreatic lipase inhibitor using their Ru (II) BIHEHP catalyst. For scaling up, Roche decided to use a heterogeneous catalyst, modified Ni /L-tartaric acid with NaBr, since this was economically more attractive. 

Orlistat Lipase inhibitor 360 mg Greater than 3 months ... 

Two possible pathways for the biosynthesis of 2-AG have been proposed (1) a phospholipase C (PLC) hydrolysis of membrane phospholipids followed by a second hydrolysis of the resulting 1,2-diacylglycerol by diacylglycerol lipase or (2) a phospholipase Ai (PLA,) activity that generates a lysophospholipid, which in turn is hydrolyzed to 2-AG by lysophospholipase C (Fig. 5) (Piomelli, 1998). Alternative pathways may also exist from either triacylglycerols by a neutral lipase activity or lysophosphatidic acid by a dephosphorylase. The fact that PLC and diacylglycerol lipase inhibitors inhibit 2-AG formation in cortical neurons supports the contention that 2-AG is, at least predominantly, biosynthesized by the PLC pathway (Stella, 1997). However, a mixed pathway may also be plausible. 

Lipase Inhibitors (drugs that prevent fat from being... 

The last class of weight-loss drugs approved by the FDA is lipase inhibitors. Drugs in this category prevent the body from absorbing fat into the bloodstream, which creates conditions that make it easier for weight loss to occur. Clinical studies have shown that lipase inhibitors produce a... 

The side effects of orlistat are extremely unpleasant. Patients may experience abdominal pain, gas, and discomfort when taking this drug the abdominal problems that occur are even more intense after the patient eats a high-fat meal. Since orlistat is a lipase inhibitor, it prevents fat from being absorbed by the body. Thus, the fat in food comes out of the body in the stool, causing these side effects ... 

Often, these effects make people stop taking lipase inhibitors almost as soon as they start it. Most patients are... 

There is not a significant abuse potential with lipase inhibitors. If abuse occurs, the patient experiences even more severe forms of the drug s already unpleasant side effects, and... 

Enantioselective hydrogenation of />-kelo esters catalyzed by the modified Raney Ni is useful for the synthesis of biologically active compounds, as shown in Figure 32.15 [56-58]. A large-scale synthesis of (-)-tetrahydroHpstatin (orlistat), a pancreatic lipase inhibitor (F. Hoffmann-La Roche AG), is carried out using this method [58]. 

Exhibit 2.11 shows two selected drugs, celecoxib (a COX-2 inhibitor) and orlistat (a lipase inhibitor), and their actions on disease targets. 

Lipase Inhibitor Orlistat (Xenical, Roche) is prescribed for the treatment of obesity. It inhibits the gastrointestinal lipase enzymes by binding to the lipase through the serine site and inactivates the enzyme. Fat in the form of triglycerides cannot be hydrolyzed by the lipase and converted to free fatty acids and monoglycerides. Thus, there is no uptake of fat molecules into the cell tissue. 

The active ingredient of Xenical, orlistat, is a pancreatic lipase inhibitor. Side-effects include faecal urgency, liquid oily stools and flatulence. Xenical capsules are administered before, during or up to 1 hour after the two main meals, twice daily. 

Orlistat is a pancreatic lipase inhibitor used in conjunction with a hypocaloric diet to reduce the absorption of dietary fat in obese patients. Orlistat is administered twice daily immediately before, during or up to 1 hour after each meal. If the meal contains no fat there is no need to take Orlistat. 

Birari RB, Bhutan KK. (2007) Pancreatic lipase inhibitors from natural sources Unexplored potential. Drug Dicov Today 12 879-889. 

Pharmacology Orlistat is a reversible lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats. It exerts its therapeutic activity in the lumen of the stomach and small intestine. 

Mecfianism of Action A gastric and pancreatic lipase inhibitor that inhibits absorption of dietary fats by inactivating gastric and pancreatic enzymes. Therapeutic Effect Resulting caloric deficit may positively affect weight control. 

Target molecule GI lipase inhibitor SERT and NET inhibitor CBi receptor antagonist... 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

Several synthetic applications are given in Scheme 16 (40). The hydrogenation of a /3-keto ester on a 6-100-kg scale is used for the synthesis of tetrahydrolipostatin, a pancreatic lipase inhibitor developed at Hoffmann-LaRoche Company (1c). Tartaric acid is the best chiral modifier a-amino acids or a-hydroxy acids are not satisfactory. The source... 

Finally, Raney nickel modified by (R,R)-tartaric acid/NaBr has been shown to be an efficient catalyst for the asymmetric hydrogenation of an intermediate in the synthesis (4) of tetrahvdrolipostatin. a pancreatic lipase inhibitor developed by Hoffmann-LaRoche (100% chemical yield, ee 90-92%, 6-100 kg scale) [76]. 

Tetrahydrolipstatin is a lipase inhibitor developed and marketed by Roche (Basel, Switzerland) as an anti-obesity drug. With the incidence of obesity rising rapidly in the industrialized nations, having reached 33% of all adults in the United States and more than a quarter of all French schoolchildren, this problem will rapidly cease to remain one of lifestyle and enter the arena of medical costs associated with the diseases stemming from obesity. 

Another type of diet pill received FDA approval in 1999. Orlistat, sold under the name of Xenical, was a lipase inhibitor. It affects the body s lipase enzyme and blocks about 30% of fat absorbed by the body. 

Orlistat is a gastrointestinal lipase inhibitor that blocks fat absorbtion in the intestine. 

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