Newer drug molecules

Necki (1886) first conceived the interesting salol principle , whereby he exploited the beneficial properties of phenols and carboxylic acids possessing potent antibacterial characteristic features into the design of newer drug molecules with better and improved pharmacological activities by means of simple esterification. 

Following are a few vital and important Docking Programmes commonly used in the design of newer drug molecules ... 

In a rather broader perspective towards the ever increasing and eternal (never-ending) search for newer drug molecules i.e., chemical entities that essentially requires specific and noteworthy biological characterstic feature do require two kinds of approaches, for instance ... 

The aliphatic moiety, R, essentially confers lipophilic characteristic properties to the newer drug molecule. 

These two aforesaid situations shall now be discussed with typical examples so that one may have a better understanding of these aspeets vis-a-vis drug design of newer targetted drug molecules. 

Besides, the actual distance existing between two vital functional moieties may be almost fixed arbitrarily in rigid molecular structural variants. These restructured and strategically positioned newer targetted-drug molecules may be subjected to vigorous and critical examinations by the aid of several sophisticated latest physicochemical analytical devices, such as X-Ray diffraction analysis Optical Rotary Dispersion (ORD) NMR-spectroscopy Mass Spectroscopy FTIR-Spectrophotometry and the like. 

Interestingly, most quantitative structural activity relationship (QSAR) studies usually commence by considering o (Hammett substitution constant) and, in case there exists more than one substituent, the a values are represented in a summed up manner as Za. Keeping in view the enormous quantum of synthetic newer target drug molecules, it has now become almost necessary and possible either to modify/refine or fine tune-up the QSAR equation. In fact, a substituent s resonance effect (R) and inductive effect (F) may be quantified as far as possible with the help of available tables of constants . In certain instances one may evidently observe that ... 

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

Newer mesalamine products utilize non-sulfapyridine methods for drug delivery. Olsalazine uses two mesalamine molecules linked together, while balsalazide uses the inert carrier molecule 4-aminobenzoyl-P-alanine. Both drugs use a diazo bond similar to sulfasalazine. Other mesalamine formulations are pH-dependent formulations that release mesalamine at various points throughout the GI tract. 

With the possible exception of maprotiline, which is chemically a modified TCA with all the side effects attributable to such a molecule, all of the newer non-tricyclic drugs have fewer anticholinergic effects and are less cardiotoxic than the older tricyclics. Lofepramine is an example of a modified tricyclic that, due to the absence of a free NH2 group in the side chain, is relatively devoid of anticholinergic side effects. Thus by slightly modifying the structure of the side chain it is possible to retain the efficacy while reducing the cardiotoxicity. 

A major advantage of the natural products approach to drug discovery is that it is capable of providing complex molecules that would not be accessible by other routes. Compounds such as paclitaxel (Taxol, 8) or rapamycin (10) would never be prepared by standard "medicinal chemistry" approaches to drug discovery, even including the newer methods of combinatorial chemistry. Likewise, the new approach of combinatorial biosynthesis, although an important one, is unlikely in the near future to yield new compounds of the complexity of paclitaxel and camptothecin. 

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