Download e-book for kindle: Drug Stereochemistry: Analytical Methods and Pharmacology, by Krzysztof Jozwiak, W. J. Lough, Irving W. Wainer

By Krzysztof Jozwiak, W. J. Lough, Irving W. Wainer

ISBN-10: 1420092383

ISBN-13: 9781420092387

ISBN-10: 1420092391

ISBN-13: 9781420092394

Drug Stereochemistry: Analytical tools and Pharmacology, 3rd Edition covers all facets of chiral medicinal drugs from educational, governmental, commercial, and scientific views, reflecting the various advances in options and technique.

Topics include:

  • The use of enzymes within the synthesis and backbone of enantiometrically natural compounds in drug discovery
  • How stereochemistry affects judgements made within the absorption, distribution, metabolism, excretion, and toxicity (ADMET) phases of drug discovery
  • Pharmacokinetics and pharmacodynamics and the problems confronted throughout the ultimate levels of the drug improvement process
  • The impression of the foreign convention on Harmonisation (ICH) at the use of unmarried isomer drugs
  • Chiral switches
  • The proposal of molecular chiral acceptance and the way it impacts the separation and behaviour of stereochemically natural drugs
  • Patent concerns surrounding chiral switches and the promoting of unmarried enantiomer switches

The publication offers a superior history on stereochemistry, from its early background, together with an outline of phrases and ideas, to the present drug improvement procedure, criminal and regulatory matters, and the recent stereoisomeric medicinal drugs. it's a one-stop reference for pharmaceutical scientists and chemists operating with chiral drug molecules.

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Additional info for Drug Stereochemistry: Analytical Methods and Pharmacology, Third Edition

Example text

Chirality 1997; 9:99–102. 3d] [12/3/012/22:6:30] [30–47] 3 Molecular basis of chiral recognition Krzysztof Jo´z´wiak INTRODUCTION Two enantiomers of a chiral substance have all their main physicochemical properties the same. Three-dimensional (3D) structures of enantiomers are nearly identical; the only difference lies in the fact that two molecules are related to each other as mirror images. Molecules are dissymmetric and any differences in the properties of enantiomers may be expressed in unequal interactions with a dissymmetric environment.

A, b, and c fragments occupy the same protein locations, the consequence of which is that the d fragment (a hydroxyl group) points into the opposite directions and interacts with different protein locations (Mg2þ or Arg119 residue for D- and L-enantiomer, respectively). The authors concluded that a similar “four-location model” is capable of explaining other stereoselective enzyme systems including mandelate racemase (10). The four-point model was found important in further studies of stereoselective binding.

For example, cytochrome P450 transformation of ifosfamide (Fig. 4) in vivo produces two dechloroethylated metabolites. P. convention, and as a result, the (R)-ifosfamide molecule (the (þ) isomer in Fig. 4) is transformed into the (S)-3-dechloroethylifosfamide metabolite (10). MIXTURES OF STEREOISOMERS Racemic mixture or a racemate is an equimolar mixture of a pair of enantiomers. The chemical name of a racemic mixture is distinguished from single enantiomer by a prefix rac-, (Æ)-, (D,L)-, or (R,S)-.

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Drug Stereochemistry: Analytical Methods and Pharmacology, Third Edition by Krzysztof Jozwiak, W. J. Lough, Irving W. Wainer

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