Therapeutic value

An impressive example of the application of structure-based methods was the design of a inhibitor of the HIV protease by a group of scientists at DuPont Merck [Lam et al. 1994 This enzyme is crucial to the replication of the HIV virus, and inhibitors have bee shown to have therapeutic value as components of anti-AIDS treatment regimes. The star1 ing point for their work was a series of X-ray crystal structures of the enzyme with number of inhibitors boimd. Their objective was to discover potent, novel leads whid were orally available. Many of the previously reported inhibitors of this enzyme possessei substantial peptide character, and so were biologically unstable, poorly absorbed am rapidly metabolised. 

Although it might seem that adrninistration of enantiomericaHy pure substances would always be preferred, the diuretic indacrinone (3), is an example of a dmg for which one enantiomer mediates the harmful effects of the other enantiomer (4). (+)-Indacrinone, the diureticaHy active enantiomer or eutomer causes uric acid retention. Fortunately, the other enantiomer distomer) causes uric acid elimination. Thus, adrninistration of a mixture of the two enantiomers, although not necessarily racemic, may have therapeutic value. 

Unlike aniracetam, pramiracetam does not appear to interact with dopaminergic, serotonergic, or adrenergic neurotransmission (72). The agent inhibits prolylendopeptidase in certain brain areas, but its inhibition constant, iC, is only 11 ]lM (69). The absence or weak activity of this compound with various neuronal systems appears to make it less likely to be of significant therapeutic value than other members of this class of agents. 

Nicotinic Receptor Agonists. There has been significant activity in the development of muscarinic cholinergic receptor agonists for dementia. In addition, agents that interact with nicotinic cholinergic receptors may also have therapeutic value. Nicotinic receptors have been reported to be... 

USP XXII specifies that sodium iodide contains 99—101.5% Nal, calculated on an anhydrous basis (4). It is used iaterchangeably with potassium iodide as a therapeutic agent, except where sodium ion is contraindicated (see Potassium compounds). Intravenous sodium iodide formulations have been used for a variety of diseases, from thyroid deficiency to neuralgia (see Thyroid and antithyroid preparations). However, these solutions are no longer listed ia the XFXUII (4), iadicatiag that their therapeutic value has not been satisfactorily demonstrated. 

It is over three centuries since cinchona bark came into use in European medicine, and no other natural drug has had so much written about it. There are the stories, sometimes legendary, of its discovery by Europeans, vigorous early discussions of its therapeutic value, the destruction of the S. American cinchona trees to meet the demand for bark, the labours of botanical explorers in collecting seed for the formation of plantations, the establishment and development of these plantations in Ceylon, India and Java, the competition between them, the gradual emergence of Java as the world s most important source of supply of cinchona bark, and the development of the manufacture of quinine sulphate in Europe, the United States and the Tropics. ... 

This chapter includes the recent various aspects of four and five membered heterocyclo-quinolines containing one nitrogen atom at the ring junction. They were subdivided according to the number of heteroatoms in the heterocyclic rings. The literature indicates that many of these heterocycles are of potential therapeutic value which leads to intensive research in the topic. On the other hand, there are various classes of heterocycles that fit under this heading but unreported yet. Consequently, efforts towards the synthesis of such unreported classes can be fruitful area of research. 

Heilung,/. healing, curing, cure. Heilungsvorgang, m. healing process. Heil-verfohren, n. healing process, -wasser, n. curative water, mineral water, -wert, m. therapeutic value. -wesen, n. medical affairs, -wirkung,/. curative effect, -wissen-schaft,/. medical science. 

The separation of enantiomers is a very important topic to the pharmaceutical industry. It is well recognized that the biological activities and bioavailabilities of enantiomers often differ [1]. To further complicate matters, the pharmacokinetic profile of the racemate is often not just the sum of the profiles of the individual enantiomers. In many cases, one enantiomer has the desired pharmacological activity, whereas the other enantiomer may be responsible for undesirable side-effects. What often gets lost however is the fact that, in some cases, one enantiomer may be inert and, in many cases, both enantiomers may have therapeutic value, though not for the same disease state. It is also possible for one enantiomer to mediate the harmful effects of the other enantiomer. For instance, in the case of indacrinone, one enantiomer is a diuretic but causes uric acid retention, whereas the other enantiomer causes uric acid elimination. Thus, administration of a mixture of enantiomers, although not necessarily racemic, may have therapeutic value. 

Again, the answer should be fairly obvious. The potential therapeutic value of the steroid hormones makes these of tremendous commercial value. The commercial market for these is of the order of hundreds of millions of dollars per year. There is no comparable market for sterols and bile salts. We are faced with the interesting situation, therefore, that sterols are relatively abundant in natural sources but of relatively low commercial value, whilst steroids occur naturally at very low concentrations but are of great commercial value. Although there are tremendous variations amongst different products, steroids with desirable properties command market prices that are (ten to one thousand fold) greater than their sterol counterparts. 

Because of the complexities resulting from the use of these relatively broadly acting COX inhibitors, the use of selective PG synthase inhibitors or receptor agonists and antagonists could provide therapeutic alternatives devoid of these side effects and therefore with therapeutic value. At this point, there are no potent and selective PG synthase inhibitors or receptor... 

Adalimumab (Humira ) is a folly human anti-TNF monoclonal antibody that is mainly used in combination with methotrexate to treat rheumatoid arthritis in adults [3]. Meanwhile, it is also used against arthritis of psoriasis and ankylosing spondylitis. Its therapeutic value in Crohn s disease is under clinical trial. 

Until quite recently, chemical interest in the metalloids consisted mainly of isolated curiosities, such as the poisonous nature of arsenic and the mildly therapeutic value of borax. The development of metalloid semiconductors, which we describe in Chapter 10, focused intense study on these elements. 

The red microalga genus Porphyridium is a source of biochemicals possessing nutritional and therapeutic values. The biochemicals include polysaccharides that have anti-inflammatory and antiviral properties, long-chain polyunsaturated fatty acids, carotenoids such as zeaxanthin, and fluorescent phycobiliproteins. 

It is misleading to consider that ROS are always deleterious, and that to prevent release or action of ail ROS will be of therapeutic value. One could reason that some ROS are released without control or purpose, as by-products of the normal metabolism of eicosanoids, or during oxidative phosphorylation in the mitochondria. However, during normal function, inflammatory ceUs appropriately release ROS both intracellularly into vacuoles and extracellularly in order to kill foreign organisms in host defence. Also, nitric oxide is a radical species whose principal role in the lung appears to be the control of pulmonary vascular tone and platelet function. Nevertheless, there are clear examples where fhistrated phagocytosis could explain an excessive release of ROS in... 

Elderberry has been referred to as "English grapes," since it is so popular as a wine ingredient. In Kent, England, elder orchards have been cultivated for the purpose of wine making. Elder flowers have been placed in wine vessels to improve the flavor of the finished product. Elder blossoms have also been infused into ales. Elderberries are often added to clarets and Bordeaux wines. Historically, it was considered improper for ladies to drink alcohol. However, elder and a dandelion wine were deemed permissible as they have therapeutic value. 

Some tumors are estrogen-dependent and the use of an antiestrogen has therapeutic value. One such antineoplastic agent appears to be patterned after clomiphene. Complex aryl ketone 204 is treated with phenyl magnesium chloride and the resulting tertiary... 

---