Lead compounds molecular modeling

Among the bis-imidazole perylenes studied, XXa is the most sensitive compound. Molecular modeling studies indicate that XXa is the most planar molecule among XXa-d. Again, a closer intermolecular interaction is attained, which presumably leads to high photosensitivity [235]. 

Ethynylation of 3j -hydroxy-16a-methyl-5a-androstan-17-one in a mixture of diethylene glycol dimethyl ether and diethylene glycol monoethyl ether in the presence of potassium hydroxide produces two isomeric 17-ethynyl derivatives. This result is not unexpected since molecular models suggest that the steric influence of the 13/ -methyl group is nearly offset by the 16a-methyl group. The presence of a 16a-acetoxy group in the estrone series also leads to the formation of epimeric 17-ethynyl compounds (61) and (62) on reaction with acetylenedimagnesium bromide. 

This review has shown that the analogy between P=C and C=C bonds can indeed be extended to polymer chemistry. Two of the most common uses for C=C bonds in polymer science have successfully been applied to P=C bonds. In particular, the addition polymerization of phosphaalkenes affords functional poly(methylenephosphine)s the first examples of macromolecules with alternating phosphorus and carbon atoms. The chemical functionality of the phosphine center may lead to applications in areas such as polymer-supported catalysis. In addition, the first n-conjugated phosphorus analogs of poly(p-phenylenevinylene) have been prepared. Comparison of the electronic properties of the polymers with molecular model compounds is consistent with some degree of n-conjugation in the polymer backbone. 

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... 

An example of a leading chemical CRO is Albany Molecular (AMRI). It had chemistry revenues 184 million in 2005. AMRI does organic synthesis and chemistry development, supported by computational chemistry for molecular modeling, with computer-assisted drug design. Furthermore, it offers different types of libraries custom, semiexclusive, focused, and natural products. Finally, AMRI conducts its own proprietary R D aimed at licensing preclinical and clinical compounds. 

---