Metabolic transformations

A closet member of this little group, revelation of whose i(>al nature requires metabolic transformation of an acetylenic linkage to an acetic acid moiety, is fl uretofen (14). The .ynthesis begins by Friedel-Crafts acylation of 2-fluorobi-phenyl (11) with acetic acid to give ketone 1. Heating with... 

Part of the reason for ortho substitution in such compounds is to decrease metabolic transformation by enzymic... 

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxyl amine leads to the hydroxamic acid 135. Reaction of... 

Csanady GA, Laib JG. Metabolic transformation of halogenated and other alkenes- a theoretical approach. Estimation of metabolic reactivities for in vivo conditions. Toxicology 1995 75 217-23. 

Darvas F, Dorman G, Papp A. Diversity measures for enhancing ADME admissibility of combinatorial libraries. J Chem Inf Comput Sci 2000 40 314-22. Klopman G, Dimayuga M, Talafous J. META. 1. A program for the evaluation of metabolic transformations of chemicals. J Chem Inf Comput Sci 1994 34 1320-5. 

Talafous J, Sayre LM, Mieyal JJ, Klopman G. META. 2. A dictionary model of mammalian xenobiotic metabolism. J Chem Inf Comput Sci 1994 34 1326-33. Klopman G, Tu M, Talafous J. META. 3. A genetic algorithm for metabolic transform priorities optimization. J Chem Inf Comput Sci 1997 37 329-34. Langowski J, Long A. Computer systems for the prediction of xenobiotic metabolism. Adv Drug Del Rev 2002 54 407-15. 

Butler TC. 1949. Metabolic transformation of trichloroethylene. J Pharmacol Exp Ther 97 84-92. 

Scheme 3, Hypothetical metabolic transformations of 2-hydroxypropylmethyl nitrosamine with the name of the originator of each hypothesis. Nameless hypotheses are by the authors.

The effects of metabolic transformations on lipophilicity can also be addressed using the difference in logP between metabolites and their parent compounds, i.e., using the... 

A second area of drug discovery and development in which enzyme reactions play a critical role is in the study of drug metabolism and pharmacokinetics. The elimination of xenobiotics, including drug molecules, from systemic circulation is driven by metabolic transformations that are entirely catalyzed by enzymes. Table 1.2 lists some of the enzyme-catalyzed transformations of xenobiotics that commonly contribute to drug molecule elimination. These biotransformation reactions... 

However, one might take the time to think back and to ask if the extensive use of such techniques might not have failed to characterize important lead compounds from plants, and especially medicinal plants. As a matter of fact, a molecule inactive in vitro might, after metabolic transformation in vivo, be effective in abrogating metastasis. The opposite is true, and promising in vitro results have often led to disappointing clinical trials. 

RPE plays numerous functions essential for proper structure and function of retinal photoreceptors. They include the maintenance of the blood-retina barrier, selective uptake and transport of nutrients from the blood to the retina and removal of waste products to the blood, enzymatic cleavage of P-carotene into vitamin A, storage of vitamin A and its metabolic transformations, phagocytosis and molecular renewal of POS, expression and secretion of growth factors and immunomodulatory cytokines (Aizman et al., 2007 Aleman et al., 2001 Crane et al., 2000a,b Elner et al., 2006 Holtkamp et al., 2001 Leuenberger et al., 2001 Lindqvist and Andersson, 2002 Maminishkis et al., 2006 Momma et al., 2003 Strauss, 2005). 

FIGURE 15.3 Hypothetical pathways responsible for carotenoid uptake, metabolic transformations, tran-scytosis to the neural retin, or secretion to the blood. 

Termination Enzymatic degradation by Reuptake into nerve terminals diffusion Metabolic transformation by... 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

The initial step after cellular uptake of T4 is metabolic transformation to 3,5,3, -tri-iodothyronine (T3) (Fig. 52-8), which interacts with cytosolic and nuclear receptors, as well as with synaptosomal membrane binding sites of unknown function [25], Cytosolic receptors are proteins of 70 kDa that do not appear to undergo translocation to cell nuclei, nor do they appear to be nuclear proteins that have leaked out of cell nuclei during cell rupture nuclear receptors are proteins of 50 70 kDa that have both DNA-and hormone-binding domains [25,26,28],... 

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