Lead compounds indispensability

Natural products are an indispensable source for novel structures and chemical diversity for drag discovery. Aquatic sources and plant sources are an underutilized source of active principles or lead compounds. 

In a chiral aldehyde or a chiral ketone, the carbonyl faces are diastereotopic. Thus, the addition of an enolate leads to the formation of at least one stereogenic center. An effective transfer of chirality from the stereogenic center to the diastereoface is highly desirable. In most cases of diastereoface selection of this type, the chiral aldehyde or ketone was used in the racemic form, especially in early investigations. However, from the point of view of an HPC synthesis, it is indispensable to use enantiomerically pure carbonyl compounds. Therefore, this section emphasizes those aldol reactions which are performed with enantiomerically pure aldehydes. 

The design aspect of host-guest chemistry mandates the knowledge-based construction of novel compounds possessing desired properties. The concept of structure seems indispensable in this enterprise, although the term is ill-defined and the International Union of Pure and Applied Chemistry (IUPAC),for instance, consciously avoids the close specification. As a corollary, many fields in science have developed their own interpretation of structure, which sometimes clash with each other and lead to misunderstandings when issues at the common interface of subdisciplines are in need of rationalization. 

RP-TLC and HPLC provide a variety of descriptors that can be used as lipophilicity indices. Among them, extrapolated capacity factors often lead to 1 1 correlation with octanol-water log P. On the other hand, isocratic capacity factors need fewer experiments to be determined however, they depend strongly on chromatographic conditions. The CHI combines easy and rapid measurements with a uniform lipophilicity scale. However, both h-pophilicity and reversed-phase chromatographic retention are composite phenomena and, consequently, their resemblance cannot always be anticipated. Because standard reference sets cannot be available for all strucmrally diverse compounds, a comparison between chromatographic indices and octanol-water log P within the series of the investigated compounds is still indispensable. 

For lead finding, the use of chemical compound collections and combinatorial libraries is indispensable to every pharmaceutical company for a timely and efficient discovery of novel bioactive entities [5]. Until recently, most attention was paid only to internal historic compound collections, maintained over several years of medicinal research [6]. Flowev-er, those libraries typically contain a limited number of structural classes as the result of past research projects which focused on biological activity islands .Today there is a growing interest in techniques that expand structural and - even more important - biological diversity, this perhaps being accomplished by the direct acquisition of an external compound collection, or by the use of internal or external synthesis capacities [7]. 

The hnge amounts of data and information alone will not be sufficient to lead to new molecnlar entities and novel therapies, since synthesizing millions of compounds will neither fill the universe of potential molecnlar structures nor allow the identification of those three-dimensional structures specifically interacting with targets. The knowledge of the biological processes and strnctnres as the templates and targets for the identification of active molecules is indispensable. 

In conclusion, animal model systems, especially heart muscle preparations, are in the end indispensable for the quantitative evaluation of the positive inotropic effect of digitalis-congeneric compounds. They appear, however, to be less suitable for the primary screening of the numerous inhibitors of NaVK -ATPase, the microscopic mechanism of which is still unknown. The observations obtained under this condition can, of course, lead to a null hypothesis concerning structure-activity relationships. 

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