Targetted drug molecule

When presented to the target, drug molecules can elicit reactions to switch on or switch off certain biochemical reactions. The main drug targets in the human body can be classified into three categories ... 

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. 

Therefore, a ereative medicinal chemist should ponder over the intricacies, complexities and legitimate presenee of eaeh funetional moiety to the overall physical chemical properties of the target-drug molecule with a view to arrive at or design safer, better and efficacious medicinal agents. Nevertheless, sueh eritieal studies have to be earried out in a rather methodical and systematic manner... 

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 ... 

Hence, during the course of designing/development of a new target-drug-molecule the medicinal chemist must take into cognizance of such metabolic phenomena and modify the structure of the drug substance in question so as to alter the course in which it should have been metabolized otherwise. 

The net result of the entire exereise was the epoch-making discovery of propranolol, that was observed to be a pure antagonist and whieh was approximately 20 times more potent in comparison to pronethalol i.e., the original targetted-drug molecule ). 

In the past one century and a half research chemists across the globe have evolved an innumerable, viable and potential synthetic routes for the preparation of any conceptualized target-drug-molecule . Interestingly, in the last four decades or so the very emergence of... 

There are a number of important considerations that have got to be followed sequentially, artistically, meticulously, and above all an individual s own skill and wisdom in accomplishing the target-drug-molecule as stated below ... 

In other words, the strategic attack on the target-drug-molecule may be conveniently and formally divided into two major components, namely ... 

It is an universal fact that a target-drug-molecule can be S3uithesized not by a particular mode of synthesis but also through several routes of S3uithetic methods. As the tai t molecules are not previously synthesized, therefore, one would not be able to predict which shall prove to be the best method of synthesis. Besides, a research chemist, with all the skills at his disposal, may also not be in a position to calculate in advance the overall nature of the various reactions involved vis-a-vis their yields of a variety of closely related as well as competitive routes of synthesis so as to profess or proclaim the best route . 

It has always been a practice to get the final or ultimate desired target-drug-molecule along with its various intermediates in its purest form achievable through chromatographic processes or recrystallization or distillation techniques. This aspect of highest purity of any compormd S3mthesized in the laboratory is of utmost importance by virtue of the fact that the subsequent physico-chemical analysis data solely depends on it. 

It is very much desired to select from the different boxes a wide range of such entities which are either very close in structure or readily convertible to, the probable functional moieties and structural types of target-drug-molecules . 

In this manner, the most suitable starting materials or intermediates to coin the desired target-drug-molecule may be deduced both logically and practically. 

Though, it is a known fact that the construction reactions are the pivotal crux in designing synthesis of a target-drug-molecule, yet there are several other crucial factors that must be borne in mind before taking on the pre-planned operation(s). A few such important factors are, namely ... 

In designing the synthesis of a target-drug-molecule it is quite natural and also common that invariably more than one functional moiety is caused to participate in arriving at the various intermediates during the course of a synthesis. It is usually a common practice adopted by the research chemists to allow one particular moiety to function as the reactive... 

A large number of target-drug-molecules invariably contain cyclic skeletons that could be either aromatic or heterocyclic in nature. Therefore, such specific reactions that help in the formation cyclic structures play a vital role in synthetic medicinal chemistry. These ringforming reactions are usually referred to as annelation reactions. 

Let us assume a target-drug-molecule A, for which there are a number of possible annelation reactions of the right-hand ring as illustrated below ... 

Ozonolysis of Cyclopentene (A) or Cyclohexene (B) to yield target-drug-molecules hav-... 

Generally, a target-drug-molecule with n chiral centres invariably has 2" possible stereoisomers. It is, however, pertinent to mention here that unless and until chiral reagents are used, optically inactive starting materials essentially give rise to optically inactive products, even though a chiral centre is formed. 

In stereochemistry, the three types of control measures viz., stereochemical, kinetic and equilibrium, the first one i.e., stereochemical control is of prime value and significance in designing a new target-drug-molecule. Therefore, the most prevalent and vital reactions that specifically afford stereochemical control are grouped together and summarized as... 

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