Biological Spectrum

The efficacy of the phenothiazines for the treatment of various psychoses led to extensive synthetic programs aimed at modulation of the biologic spectrum of these molecules. As seen elsewhere, much of this work has centered on changes of the nature of the atoms that constitute the center ring. Thus, for example, it has proven possible to replace the nitrogen atom of the phenothiazine by carbon while maintaining neuroleptic activity. 

The Protos warfare on their Lept neighbors depended heavily on chemicals, but ants are by no means unique in making extensive use of chemicals for communication and warfare. From one-celled organisms to complex plants and animals, many living creatures do the same. As species develop over evolutionary time, it is relatively easy for them to adapt their cellular machinery to producing chemicals for communication, warfare, and other purposes. These chemicals facilitate the way of life of organisms spread all across the biological spectrum. 

These examples (Figure 13) clearly show that, although there are very close chemical relationships within a class of compounds, there may be remarkable differences in the biological and biophysical properties. This enables the use of various compounds for specific purposes although their biological spectrums may overlap (4, ,7 8, ). 

As In the use of dichlobutrazole and paclobutrazole, the biological spectrum of the two experimental compounds S 3307 and S 3308, whether fungicide or growth regulator, Is dictated only by the substitution pattern In one part of the molecule. Triapenthenol, which Is of particular Interest as a growth regulator in rice and rape, also possesses a marked fungicidal activity. 

B. Biological Spectrum and Potency Significantly Enhanced—In Vivo Studies... 

The wide biological spectrum characterizing both natural and synthetic steroids has made this group of compounds one of the most important classes of biologically active materials. As a result of an almost unprecedented number of structural modifications, it has become possible to introduce highly active specific dependable and last, but not least, economically producible derivatives into therapy. 

The introduction of a 16a-hydroxy group into 6a,9-difluoro-prednisolone led to a compound (fluocinolone) with the anticipated favorable biological spectrum, namely high anti-inflammatory activity (35-fold that of hydrocortisone, seven-fold that of triamcinolone) and - in contrast to the C-16 unsubstituted compound - no retention of sodium. The corresponding 16,17-acetonide (fluocinolone acetonide) exhibited 100-fold the anti-inflammatory activity of hydrocortisone, with no sodium retention. In clinical trials, 6a,9-difluoro-16a-hydroxyprednisolone was found to be a potent suppressor of inflammatory conditions such as rheumatoid arthritis, as well as allergic conditions such as asthma, whilst its acetonide proved to be highly effective as topical corticoid. 

The introduction of a 16a-hydroxyl group into 6a,9-difluoro-prednisolone led to 6a,9-difluoro-16a-hydroxy-prednisolone with an anticipated favorable biological spectrum. 

In short, the biological spectrum of progesterone is the sum total of the events initiated by progesterone itself as well as by its metabolic products and is influenced by its physical form, route of administration, site of metabolism, blood and tissue levels, type of binding, etc. Among the biologic events attributed to progesterone and its metabolites are ... 

Melittin. Melittin, the main toxin of bee venom, has a diverse biological spectrum and can lyse cells. Although it is tempting to associate its activities with channel formation, melittin activates G proteins (145) and also binds to calmodulin. The melittin sequence reveals a hydrophobic N-terminus... 

In addition to the originally observed antifungal activity, phytoalexins exhibit toxicity across much of the biological spectrum, and their activity is not confined to microorganisms (29). 

The special biological spectrum - especially against difficult to control monoco-tyledonous weeds - and the selectivity in cereals led to development of two compounds, later known as fiucarbazone-sodium (1) and propoxycarbazone-sodium (2). 

This can be attributed to the discovery of the latest generation compounds with a substantially broader biological spectrum. More than 15 companies, including most major players and also many smaller competitors, have been involved in these efforts. 

The first representative of the new chemical class spiroketalamine within the amine fungicide group is spiroxamine, which was introduced to the public in 1996 (Table 17.22) [102]. Its chemistry and stereochemistry have been described by Kramer et al. [103, 104] and the biological spectrum has been characterized by Dutzmann [105]. 

In summary, diafenthiuron remains a singular active ingredient in crop protection chemistry because of its unique chemical class and biochemical mode of action. Owing to its unparalleled biological spectrum, translaminar and gas-phase activity, selectivity towards beneficial arthropods and the lack of cross resistance... 

Table 2 Biological spectrum of Cyclohexyl-benzothiophen-2-carboxamid-S,S-dioxid (Preventol TP OC 3082) in ppm.

The stereospecific synthesis of the cis-norisopyrethrinic acid 231 deserves particular interest. This is an acid component for highly active pyrethroid esters with a very interesting biological spectrum (Reaction scheme 156). Usually the Horner olefmation gives Z/E-mixtures [455], but by applying cyclic phosphonic esters 232, one obtains only the Z-isomers [456, 922]. 

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