Structural analog approach

In the recently published structural analog approach [44], logP of unknown chemicals is calculated from the known experimental log P of their closest struc-... 

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. JL Fauchere, ed. QSAR Quantitative Structure-Activity Relationships m Drug Design. New York Alan R Liss, 1989, pp 177-181. 

This laboratory has utilized two approaches to define further the anticonvulsant properties of PCP. One approach involved a relatively simple convulsant model, pentylenetetrazol-induced convulsions. In this model, the administration of ketamine alone, or in combination with several known anticonvulsants, was tested. Ketamine, as a structural analog of PCP, shares many of the pharmacological properties associated with PCP. The second approach involved a more complex model, hippocampal-kindled seizures. 

The variation in the antiscorbutic activity displayed by the various analogs of L-ascorbic acid makes it abundantly clear that the activity is dependent upon the stereochemical configuration of the molecule as a whole, and it would appear that the more closely the structure of a particular analog approaches that of the natural Vitamin C the greater will be the antiscorbutic power. Support for this view is illustrated by 6-desoxy-L-ascorbic acid which is obtained from L-sorbose.2 -80 Condensation of L-sorbose with acetone gives a mixture of 2,3-isopropylidene-L-sorbose (LII) and the diisopropylidene derivative. Treatment of LII with p-toluenesulfonyl chloride yields l,6-ditosyl-2,3-isopropylidene-L-sorbose (LIII). The greater reactivity of the tosyl group at C6 enables... 

There are many structural possibilities for attaching dihydrogen to the methonium ion, but, by analogy to the CH5 structures, the approach... 

If we consider how one might potentially go about developing a rational strategy for designing a less toxic structural analog of a known toxic chemical, three general approaches can be applied, based on ... 

Recent years have seen limited advances in formulating quantitative prediction correlations for hydrolysis rate constants. Fortunately numerous experimental studies provide pH-dependent hydrolysis rate constants for one or more compounds in most classes of organics that might be of environmental concern. Estimation of reactivity by comparison with structural analogs within a given class is often the fastest and most reliable approach. 

With an increasing number of novel lead candidates that enter into preclinical development, considerable resources are needed to identify impurities. LC/MS-based approaches provide integrated sample cleanup and structure analysis procedures for the rapid analysis of impurities. This advantage was demonstrated during the preclinical development of TAXOL . LC/MS played an important role for the identification of impurities contained in extracts and process intermediates from Taxus brevifolia and T. baccata biomass. Because drugs derived from natural sources often have a very diverse set of structural analogs, it is important to determine which... 

The numerical coefficient of 2 appears because one electron is present in each of the interacting nonbonding orbitals. An analogous approach (structures 14-16) shows that the resonance energies of 9,10 and 11 are... 

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