Lead compounds biological activity

Original chemical research is also at the origin of the discovery of the benzodiazepines by Stembach. By the way, this author specifies that the class of compounds he was seeking had to fulfill fhe following criteria (1) the chemical series had to be relatively unexplored, (2) it had to be easily accessible, (3) it had to allow a great number of variations and transformations, (4) it had to offer some challenging chemical problems and (5) it had to look as if it could lead to biologically active products. 

The C-nucleosides 179,180 and 181, analogues of some of the most active anti-HIV nucleosides, have been prepared (Fig. 31). The rationale for this work, the same than for all the C-nucleoside syntheses, is that the isosteric substitution of nitrogen by carbon may lead to biologically active compounds, in which the glycosidic bond is more stable than that of regular nucleosides. This aspect in the cases of the particularly unstable 2, 3 -dideoxy and 2, 3 -dideoxy-2, 3 -didehydronucleosides is an important characteristic. The chemistry and biochemistry of C-Nucleosides have been reviewed [23, 214-218]. This section deals only with the synthesis of 2, 3 -dideoxy-C-nucleosides which have been... 

The results presented here show that introduction of hetero atoms into the sidechain of the benzamide herbicides leads to biologically active compounds. The most active of these heteroalkyl analogs, 4b, possesses a similar weed spectrum and rate of use as for EL-107. In no case, however, did any of the analogs show activity superior to EL-107. 

COMPOUNDS OF GERMANIUM, TIN AND LEAD INCLUDING BIOLOGICAL ACTIVITY AND COMMERCIAL APPLICATION... 

The objective of this study is to show how data sets of compounds for which dif-ferent biological activities have been determined can be studied. It will be shown how the use of a counter-propagation neural networb can lead to new insights [46]. The cmpha.si.s in this example is placed on the comparison of different network architectures and not on quantitative results. 

Diverse libraries can be used for lead finding by screening against several different targets. The selected compounds should cover the biological activity space well. 

Fig. 7. The cycle of stmcmie-based dmg design. The conventional or basic cycle consists of a simple loop between chemical synthesis and biological activity. This cycle is typically initiated through a lead compound. Whereas this cycle remains the core of the dmg discovery process, the resources available...

It would not be too far fetched to state that life on this planet is totally dependent on two compounds based on the purine nucleus. Two of the bases crucial to the function of DNA and flNA—guanine and adenine—are in fact substituted purines. It is thus paradoxical that the lead for the development of medicinal agents based on this nucleus actually came from observations of the biologic activity of plant alkaloids containing that heterocyclic system, rather than from basic biochemistry. 

With very few exceptions, the biological activities of synthetic steroids tend to parallel those of the naturally occurring hormones on which they are patterned. Compounds with distant pharmacological activity are, as a rule, quite rare. It is thus intriguing that inclusion of a tertiary amine at the 11 position of a pregnane leads to a compound with activity far removed from its close analogues. The agent in question, minaxalone (47), exhibits anesthetic activity. 

A series of benzimidazole and benzimidazolone derivatives from the Janssen laboratories has provided an unusually large number of biologically active compounds, particularly in the area of the central nervous system. Reaction of imidazolone itself with isopropenyl acetate leads to the singly protected imidazolone derivative 51. Alkylation of this with 3-chloro-l-bromopropane affords the functionalized derivative Use of this... 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

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