More notable examples

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

Many researchers have applied similar approaches to develop or apply linear free energy relationships, when the substituent is directly attached to the double bond, with some success. Two of the more notable examples can be found in the Patterns of Reactivity Scheme (Section 7.3.4) and the works of Giese and coworkers.16 19... 

Although banned by the IOC in 1974, AASs have been continued to be used. Among the more notable examples is the disqualification of Ben Johnson at the 1988 Seoul Olympic Games. Johnson, whose urine contained metabolites of the anabolic steroid stanazalol, had won the 100-meter dash gold medal in world record time. He was disqualified and his medal returned. Johnson was subsequently banned for life following another positive test, of another nature (discussed later), in 1993. 

The extreme susceptibility of open dilactone 545 to transannular cyclization under both alkaline and acidic conditions has also been established.429,431 Several more notable examples are illustrated in Scheme 81. Such reactivity has been attri-... 

In the last 30 years there have been continued instances of drug recalls or precautionary statements due to pharmacovigilance reports and some more notable examples include benoxaprofen and hepatic disorders/ deaths in the elderly and temafloxacin associated hemolytic anemia. Other recent examples are cardiac valve disorders from fenfluramine and phentermine (Fen-Fen), anaphylaxis from zomepirac, rhabdomyoly-sis associated with ceiivastatin and cardiac arrests from drug interactions with terfenadine and drugs which inhibit P450 3A4 like ketoconazole and erythromycin... 

One of the more notable examples of this new approach came in 2001 in the Caiskill Mountaitts of New York, where the Eastern New York Chapter... 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

The base-catalysed isomerisation of thiazoles to imidazoles initially reported by Cook et al " has been further investigated more recently. One notable example reports the reaction of 2-amino-2-cyanoacetamide 37 with benzylisothiocyanate to give 5-... 

Many of the alloys of copper are more resistant to corrosion than is copper itself, owing to the incorporation either of relatively corrosion-resistant metals such as nickel or tin, or of metals such as aluminium or beryllium that would be expected to assist in the formation of protective oxide films. Several of the copper alloys are liable to undergo a selective type of corrosion in certain circumstances, the most notable example being the dezincification of brasses. Some alloys again are liable to suffer stress corrosion by the combined effects of internal or applied stresses and the corrosive effects of certain specific environments. The most widely known example of this is the season cracking of brasses. In general brasses are the least corrosion-resistant of the commonly used copper-base alloys. 

The scientific and technical corrosion literature has descriptions and lists of numerous chemical compounds that exhibit inhibiting properties. Of these only a very few are ever actually used in practical systems. This is partly due to the fact that in practice the desirable properties of an inhibitor usually extend beyond those simply relating to metal protection. Thus cost, toxicity, availability, etc. are of considerable importance as well as other more technical aspects (see Principles). Also, as in many other fields of scientific development, there is often a considerable time lag between laboratory development and practical application. In the field of inhibition the most notable example of this gap between discovery and application is the case of sodium nitrite. Originally reported in 1899 to have inhibitive properties, it remained effectively unnoticed until the 1940s it is now one of the most widely employed inhibitors. 

The influence of antimony at a level of 300 ppm in copper electrolysis is also significant. The morphologies of deposits made from a pure acid-copper sulfate electrolyte and from an identical solution to which the antimony was added are shown in Figures 5 and 6. There are many other combinations of impurities and electrolytes which exhibit this changing surface appearance and deposit orientation besides those selected as examples. Anion effects are also not uncommon, with the halogens often causing the more notable changes. 

Some ridge sections are underlain by mantle melt anomalies, or hot spots, such as at the Azores and Galapagos Islands. These are marked by the stars in Figure 19.1 and data points 12 and 13 in Figure 19.5. Mantle upwelhng beneath both these ridge sections has abnormally thickened the oceanic crust to at least about 10 km. Most of the 47 known hot spots lie more than 500 km from a ridge axis. The Hawaiian islands are a notable example. 

Although boranes and hydrocarbons are more notable for their differences than for any similarities, there are several important hydrocarbon systems that adopt structures that conform to the borane pattern (202). They include tnetal-hydrocarbon v complexes, various aromatic systems, and certain other neutral or charged hydrocarbons. Representative examples are listed in Table VII. 

The known variability associated to the behavior of Caco-2 cell lines, together with the need to find a more robust and easy to grow type of culture led the pharmaceutical industry to substitute this system by, for example, MDCK cell cultures. So in silico modelers have also turned towards this new kind of in vitro cell data, although to a lesser extent than with Caco-2 systems. Perhaps the only notable example of the use of MDCK data is Refsgaard s categorical model, where a dataset of Caco-2 permeability values was enriched with MDCK permeability data [99]. 

A number of examples involving nitrile oxide cycloadditions to cyclic cis-disubstituted olefinic dipolarophiles was presented in the first edition of this treatise, notably to cyclobutene, cyclopentene, and to 2,5-dihydrofuran derivatives (15). The more recent examples discussed here also show, that the selectivity of the cycloaddition to 1,2-cis-disubstituted cyclobutenes depends on the type of substituent group present (Table 6.8 Scheme 6.41). The differences found can be explained in terms of the nonplanarity (i. e., pyramidalization) of the double bond in the transition state (15) and steric effects. In the cycloaddition to cis-3,4-diacetyl-(197) and cis-3,4-dichlorocyclobutene (198), the syn-pyramidalization of the carbon atoms of the double bond and the more facile anti deformability of the olefinic hydrogens have been invoked to rationalize the anti selectivity observed. 

Sadly, there are a few exceptions to the tidy picture presented by the Aufbau filling diagram. Copper, chromium, and palladium are notable examples (see Chapter 22 for details). Without going into teeth-grinding detail, these exceptional electron configurations arise from situations where electrons get transferred from their proper, Aufbau-filled orbitals to create half-filled or entirely filled sets of d orbitals these half- and entirely filled states cire more stable than the states produced by pure Aufbau-based filling. 

The most notable example of live attenuated vaccines is the smallpox vaccine, first developed by Edward Jenner, although the origin of the vaccine (vaccinia virus) remains obscure. More recent examples of live attenuated vaccines include most of the viral vaccines currently in use, such as measles/mumps/rubella (MMR) and varicella zoster (VZV) vaccines, and some... 

The stability of excipients is almost always taken for granted. Obviously, there is the potential for a phase change with certain lower melting excipients, e.g., semisolid materials, however, this is not a chemical phenomenon although it may enhance the potential for interaction by increasing the effective interface available at which the interaction can take place. However, some materials are not stable under conditions encountered in excipient compatibility screening or accelerated stability testing. A notable example is dibasic calcium phosphate dihydrate. At temperatures as low as 37°C, under certain conditions, the dihydrate can dehydrate to form the anhydrous material with the concomitant loss of water of crystallization (25), and at 25°C, it is a stable solid with a shelf life, when stored correctly, of more than two years. 

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