Pharmaceuticals antipsychotic agents

Derivatives of 11 //-dibenz[6,e]azepine (morphanthridines) and 5/2-dibenz[Z>,/]azepine are valuable, commercial pharmaceutical products. The most important derivatives are the antidepressant, Depramine (16),30 the antiepileptic, Carbamazepin (17),62 the hypnotic agents Perlapine (18),63-64 and its 2-fluoro derivative (Fluperlapine),65 and Opipramol (19), an antidepressant and antipsychotic agent.66... 

A number of the major pharmaceutical companies have used biocatalytic approaches based on esterases and lipases to prepare target drugs or intermediates.107 183 187 Most of these approaches involve resolutions that use a racemic ester or amide as substrate, whereby yields of 50% can only be realized. Examples of resolutions applied to pharmaceutical intermediates such as the paclitaxel (Taxol ) sidechain and J -(+)-BMY-14802, an antipsychotic agent, have been described by the Bristol-Myers Squibb group.107... 

It is worth noting that the Shibasaki group also developed a highly useful protocol for asymmetric Mannich-tyip reactions (556), which was used successfully in the synthesis of biologically active molecules like nemonapride, an antipsychotic agent developed by Yamanouchi Pharmaceutical. Since such a useful application of this methodology is not a bom fide natural product synthesis, a detailed discussion is beyond the scope of this contribution and the interested reader is referred to Shibasaki s original report (556). 

Pnor to 1975, discussions of fluonnatcd pharmaceuticals focused mainly on anti-mflammatory steroids, antipsychotic phenothiazines, and 5-fluorouraciI and Its derivatives as anticancer agents [/ 2] Dunng the past 25 years, and especially in the last decade, tluonnated dmgs have been marketed for the treatment of a wide variety of diseases This section will focus on those presently marketed drugs where the presence of fluonne has produced significant therapeuhc advantages... 

Many variants of the dopamine receptors have been tested for association with psychiatric and drag response phenotypes (42). These studies have been based on the candidate gene hypothesis, which argues as follows Because antipsychotic pharmaceutical agents target dopamine receptors, especially the D -hke receptors, disruptions in the receptors, and accessory proteins, may be the cause of disease (3). 

Pyrazoles, pyrazolines, and pyrazolones have all found wide use in many fields. Their greatest utility resides in pharmaceuticals, agrochemicals, dyes (textile and photography), and to a lesser extent in plastics. The main uses of the pharmaceuticals that incorporate the pyrazole nucleus are as antipyretic, antiinflammatory, and analgesic agents. To a lesser extent, they have shown efficacy as antibacterial/antimicrobial, antipsychotic, antiemetic, and diuretic agents. 

Chemical/Pharmaceutical/Other Class Neuroleptic agent, antipsychotic, major tranquilizer... 

Microencapsulated solid preparations are widely used in pharmaceutical, chemical, and other industries to protect various substances from environmental impact, as well as for extending their action [137], In the pharmaceutical field, in particular, these preparations are mainly used to get controlled release drug kinetics, to minimize side effects, to reduce gastric irritations, and to mask the unpleasant taste of the contained drug [137-142]. Indeed, many different active components are microencapsulated analgesics, antibiotics, antihistamine, cardiovascular agents, iron salts, antipsychot-ics [143], vitamins, peptides [144], proteins [145], antiasthma [140,146], broncodilators, diuretics, anticancerogens, tranquilizers, and antihypertensives [137],... 

A large number of unnatural molecules derived from these heterocycles are of great pharmaceutical importance, many of them being drug molecules currently in the market. Representative examples are shown in Figure 3.2, and include the antipsychotic haloperidol, the antidepressant paroxetine, the anti-HIV palinavir, the antihypertensive amlodipine, the cholesterol-lowering agent torcetrapib, and the mitosis inhibitor monastrol. 

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