Lead compounds finding

The first step in designing a new compound is to find compounds that have even a slight amount of usefulness for the intended purpose. These are called lead compounds. Once such compounds are identified, the problem becomes one of refinement. Computational techniques are a fairly minor part of finding lead compounds. The use of computer-based techniques for lead compound identification is usually limited to searching databases for compounds similar to known lead compounds or known to treat diseases with similar causes or symptoms. 

Certain base adducts of borane, such as triethylamine borane [1722-26-5] (C2H )2N BH, dimethyl sulfide borane [13292-87-OJ, (CH2)2S BH, and tetrahydrofuran borane [14044-65-6] C HgO BH, are more easily and safely handled than B2H and are commercially available. These compounds find wide use as reducing agents and in hydroboration reactions (57). A wide variety of borane reducing agents and hydroborating agents is available from Aldrich Chemical Co., Milwaukee, Wisconsin. Base displacement reactions can be used to convert one adduct to another. The relative stabiUties of BH adducts as a function of Group 15 and 16 donor atoms are P > N and S > O. This order has sparked controversy because the trend opposes the normal order estabUshed by BF. In the case of anionic nucleophiles, base displacement leads to ionic hydroborate adducts (eqs. 20,21). 

Catalysts were expensive, however, so the petroleum industry did not solve the problem of cheap, lead-free, knock-free gasoline until the 1970s, after General Motors adopted the catalytic converter. Lead compounds inactivate the catalysts, and sophisticated catalytic cracking techniques had to be developed to replace the fuel additive. Ironically, an even more difficult job was finding a substitute for the protective coating that tetraethyl lead formed on exhaust valve seats not even newly developed, extremely hard materials prevent wear and tear on them as well as tetraethyl lead did. 

The development of new chemotherapeutic agents for a particular disease state continues to depend to a significant degree on the discovery of a lead compound , which can be further developed into a viable drug candidate. A very important aspect of this process is to find novel substances that will provide a new mode of action for the treatment of a specific disease. From a historical standpoint, the isolation of novel substances from natural sources has often provided this lead compound. The number of new drugs and their origin for the period 1981-2002 has recently been summarized [1], and, of 79... 

Objectives Optimize biological activity of drugs Find new active lead compounds Characteristics Response in isolated systems Effects are specific and well defined Specific mechanism of action Receptor is known in most cases Techniques Hansch Approach Multivariate Analysis Computerized molecular modeling Estimate rates of fate processes Analyze Processes Whole organism response Net effects (mortality growth, etc.) Specific nonspecific mechanisms Receptor unknown in most cases Hansch Approach Multivariate Analysis Molecular modeling not applied... 

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