Pharmacological value, compounds

The strains described in Table 9.4 are all of commerdal value since they produce compounds which are either pharmacologically active or can be converted to pharmacologically important compounds. For example, the production of 1,4-androstadiene-3,17-dione from (5-sitosterol provides material which can be readily converted to estrone, while 4-androstene-3,l 7-dione can be converted to testosterone. 

ApA2 values represent the negative log to the base 10 of the average concentration (M) of an antagonist which will reduce the response of the uterine horn 2X units of pharmacologically active compound (agonist) to X units of the agonist. 

Transition metal-catalyzed hydrovinylation is one of a few practically useful carbon-carbon bond-forming reactions utilizing feedstock carbon sources for the synthesis of high-value fine chemicals. Asymmetric hydrovinylation has many potential applications in the synthesis of pharmacologically important compounds, such as ibuprofen and naproxen, and has attracted much attention [110]. Recently, chiral monodentate phosphines have proven to be highly efficient ligands for the asymmetric hydrovinylation of a-alkyl vinylarenes [111]. 

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an essential enzyme required for normal folate metabolism in prokaryotes and eukaryotes. Its role is to maintain necessary levels of tetrahydrofolate to support the biosynthesis of purines, pyrimidines and amino acids. Many compounds of pharmacological value, notably methotrexate and trimethoprim, vork by inhibition of DHFR. Their clinical importance justified the study of DHFR in the rapidly evolving field of enzymology. Today, there is a vast amount of published literature (ca. 1000 original research articles) on the broad subject of dihydrofolate reductase contributed by scientists from diverse disciplines. We have selected kinetic, structural, and computational studies that have advanced our understanding of the DHFR catalytic mechanism with special emphasis on the role of the enzyme-substrate complexes and protein motion in the catalytic efficiency achieved by this enzyme. 

Other ergoline derivatives of potential pharmacological value that have been reported include the nitroso-compounds (49) and (50), which show some activity against L 1210 leukaemia in mice, and the elymoclavine-derived urethane (51),... 

Noting the similarity of tetrazole pK values to those of carboxylic acids, tetra-zoles have often been used as bioisosteric replacements for CO2H in pharmacologically active compounds. Tetrazoles alkylate and acylate on N-1 or N-2 depending on substituents at C-5, however selective 1-alkylations by quatemisation of 2-tri-w-butylstannyl derivatives have been reported. ... 

Quinazohnone derivatives attract widespread attention due to the diverse biological activities associated with them. Rutaecarpine (Fig. 13.7) and luotonine A [80] (Fig. 13.8) are the two natural quinazoline-fused compounds exhibiting very potent pharmacological values. 

Hence, two drugs of similar ogP may differ greatly in logZ) at physiological pH, with profound consequences for their pharmacological activity. As a consequence, log/ values of ionizable compounds are often quoted at pH 7.4, and equations similar to those above are used in pH-metric techniques [117-124] to determine either log/ or logZ). A compilation of the principal relationships linking partition and distribution coefficients is available in Refs. 125 and 126. 

Ideally, future antineoplastic drug discovery should be based on a more rational, botanical, chemical, and pharmacological approach. A possible way to test the antineoplastic effects of compounds would be to use some semi in vitro-in vivo models. A more rational approach in antineoplastic research, combined with the enormous chemodiversity of flowering plants, will lead to the discovery of several molecules of clinical value. 

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