Antiobesity agents

B. Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide homoallylic alcohol in high yields (>94%) and excellent diastereoselectivity (dr >98 2). The presence of a phase-transfer catalyst (e.g., B114NI) significantly accelerates the rate of reaction, whereas adding fluoride ion retards the reaction (Eq. 8.70).165 The method was applied to the asymmetric total synthesis of the antiobesity agent tetrahydrolipstatin (orlistat).166... 

J )-Mandelic acid 3 is a useful chiral synthon for the production of pharmaceuticals such as semi-synthetic penecillins, cephalosporins and antiobesity agents and many methods have been reported for the preparation of the optically pure material. A method to deracemize the racemate which is readily available on a large scale was developed by Ohta et al. using a combination of two biotransformations. The method consists of enantioselective oxidation of (S)-... 

Antmomyces Antinutrient Antiobesity agents Antiobesity drugs Antioxidant Antioxidant 330... 

Leptin is a peptide hormone secreted by adipocytes. Recombinant human leptin has been investigated for its potential as an antiobesity agent [105,106]. Women with hypothalamic amenorrhea display reduced levels of leptin. Leptin administration to these women improves reproductive and neuroendocrine function [107], Nasal administration of leptin to rats in the presence of either TDM (1) or LPC [108] caused a significant increase in serum leptin levels. Increased serum leptin levels were associated with reduced food consumption [108], The development of an effective nasal formulation of leptin containing an absorption enhancer may allow more frequent dosing with leptin and thereby overcome the limited efficacy observed following subcutaneous injections of large doses of this hormone. 

Moreover, genetic or pharmacological interruption of CBi receptor activity results in enhanced anxiety- and depressive-like states in rats and mice (Haller et al., 2002, 2004a,b Marsicano et al., 2002 Martin et al., 2002 Navarro et al., 1997 Uriguen et al., 2004). Severe adverse psychiatric events, mainly depression and anxiety, were observed in obese patients treated with SR141716 (rimona-bant), a C1B r receptor antagonist previously in the market as an antiobesity agent (Christensen et al., 2007). 

Heymsfield, S.B., Allison, D.B., Vasselli, J.R., Pietobe 11 i, D.G. and Nunthe, C. (1998) Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent. A randomized control trial. Journal of the American Medical Association 280, 1 596-1 600. 

Sibutramine inhibits neuronal reuptake of NE and serotonin (similarly to antidepressants, p. 226). It diminishes appetite and is classified as an antiobesity agent (p.328). 

Title Substituted Azole Acid Derivatives Useful as Antidiabetic and Antiobesity Agents and Method... 

Ro 16-8714 (84) is a tertiary amine also developed as an antiobesity agent. It normalizes blood glucose in ob/ob mice [376] and in streptozotocin-diabetic rats [377] by increasing glucose oxidation. A euglycaemic clamp in fa/fa rats determined that the compound increases both basal and insulin-stimulated glucose utilization in brown adipose fat, the tissue in... 

Lipstatin is a natural product that exhibits potent inhibitor activity of the pancreatic lipase, and therefore it is a potential lead for the development of antiobesity agents. P.J. Kocienski developed a synthesis for this compound that incorporates an aldehyde-ketene cycloaddition as the key step. The reaction between the aldehyde and silylketene derivative was carried out in the presence of EtAICIs that served as the Lewis acid activator. This transformation led to the formation of four diastereomers in 91% yield, but after desilylation, the desired stereoisomer could be isolated in 64% yield from the mixture. 

Bays, H. E. (2004). Current and investigational antiobesity agents and obesity therapeutic treatment targets. Obes Res 12(8) 1197-211. 

Organosulfur compounds have been incorporated into various different classes of molecules, which have pharmaceutical utility as anti-inflammatory agents, analgesics, antiarrhythmic agents, antibiotics, antiobesity agents, and so... 

As stated earlier, RXR is a promiscuous dimerization partner for several nuclear receptors, including those related to lipid physiology, such as PPARs, LXRs and FXRs [112]. Since RXR-selective ligands can elicit similar activities to ligands of the heterodimer partner receptors, it is believed that these agents may be useful as antidiabetic and antiobesity agents [113]. 

This section covers compounds that were reported relatively recently. The mechanism of action of these compounds is reasonably understood. The compounds in this section have been sorted by their biological activity and their potential utility in the clinic. The class of compounds include immunosuppressants (rapamycin and FK506), antitumor agents (geldanamycin to echinomycin), antiinflammatory agents (efomycin), antiobesity agents (lipstatin), and antibiotics (streptogramins to platensimycin). 

Since one of the metabolic changes associated with some types of obesity in human beings and rodents is increased fatty acid synthesis, inhibitors of lipogenesis are sought as antiobesity agents. This area has been reviewed recently. ... 

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