Biotransformations : a survey of the biotransformations of by D R Hawkins PDF

By D R Hawkins

ISBN-10: 1847550274

ISBN-13: 9781847550279

Now in its 7th amazing quantity, Biotransformations has develop into validated as a distinct and demanding resource for these inquisitive about the invention and improvement of recent compounds. It widely covers the clinical literature for the interval 1987 to 1994. The sequence presents an entire survey of the biotransformations, in vertebrates, of the subsequent: prescribed drugs; agrochemicals; nutrition ingredients; environmental chemical substances; commercial chemical substances. Biotransformations offers a prepared approach of getting access to info at the identified pathways for the biotransformation of structurally-related compounds. Key useful teams supply an index-related process for retrieving details on compounds of curiosity. a different index permits the retrieval of examples of particular biochemical reactions that may have wider program. every one quantity corresponds approximately with the medical literature released in the course of a calendar yr. each one quantity encompasses a assessment bankruptcy which discusses examples of novel biotransformations, species variations, stereochemical facets and mechanisms of toxicity linked to particular biotransformations. learn more... summary: Now in its 7th impressive quantity, Biotransformations has develop into validated as a distinct and demanding resource for these occupied with the invention and improvement of recent compounds. It greatly covers the medical literature for the interval 1987 to 1994. The sequence presents an entire survey of the biotransformations, in vertebrates, of the subsequent: prescribed drugs; agrochemicals; nutrition ingredients; environmental chemical substances; commercial chemical compounds. Biotransformations presents a prepared approach of gaining access to info at the recognized pathways for the biotransformation of structurally-related compounds. Key practical teams supply an index-related approach for retrieving details on compounds of curiosity. a different index permits the retrieval of examples of particular biochemical reactions which could have wider program. each one quantity corresponds approximately with the medical literature released in the course of a calendar 12 months. each one quantity encompasses a overview bankruptcy which discusses examples of novel biotransformations, species modifications, stereochemical facets and mechanisms of toxicity linked to particular biotransformations

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Sample text

263). Similarly haloperidol (136) contains a substituted piperidine group and could form pyridinium compounds in vivo. Metabolites of haloperidol and its dehydration product (137) have been studied in mice (p. 265). Two pyridinium metabolites (138) and (139) were identified as urinary metabolites but these were only detected in brain tissue of animals treated with the dehydration product (see also Vol. 5, pp. 266-267). It is postulated that the nitrosourea (140) degrades to an intermediate 19 isocyanate (141) in vivo which subsequently reacts with nucleophilic entities such as glutathione.

The formation of N-glucuronides of various model compounds containing five-membered ring nitrogen heterocycles has been investigated in vitru using liver microsomes from various species (p. 252). Generally, there was low reactivity for nitrogens adjacent to a substituted carbon such as the substituted imidazole (59). The highest reaction rate was observed with the tetrazole (60) followed by the 1,2,3-triazole (61). For the latter compound there was a species difference with monkey and rat showing a preference for formation of the N'- and N2-glucuronides respectively.

With rabbit liver preparations (1) was also hydrolysed to the aniline (4) and hydroxylated to the N-hydroxyaminofluorene (6) as well as to the glucoloylamide ( 5 ) and also hydroxylated in the ring systems to the 5-, 7- and 9-01s (8), (9) and (2). In addition to the formation of the ketone (3), this intermediate was further hydroxylated by one of the rabbit liver preparations to the 5- and 7-hydroxy-9-ones (10) and (11). The ketone (3) was shown to be reduced by the rat liver preparation to the optically active 9-hydroxyacetylaminofluorene ( 2 ) and was also hydroxylated to (11).

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Biotransformations : a survey of the biotransformations of drugs and chemicals in animals. Vol. 7 by D R Hawkins


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