Oh Ci Ocor etc

When the carboxyl moiety of the CDA is thus activated, often to the acid chloride, (partial) racemization of the reagent may be a possibility, depending on the nature of the acid used and reaction conditions of activation. In some of the reports using such activation, it was ascertained that no significant racemization occurred, but in many other studies no such check was made. Initial studies on the GLC separation of enantiomeric alcohols as esters of various chiral acids used packed columns...

Kidney

The major functions of the kidney include the regulation of water, electrolyte and nutrient balance of the body, and the excretion of metabolic waste products and foreign substances. These functions are carried out by a series of complex Interactions involving the filtration, reabsorption, and secretion of plasma water and its constituents. The major structural and functional unit of the kidney is the nephron (Fig, 10). Each kidney is composed of approximately 1 million nephrons (9). A complete...

Resolutions via Derivatization of Epoxides

Metabolic epoxidation of carbon-carbon double bonds in alkenes and arenes is a fundamentally important biotransformation of foreign compounds. The primary epoxide (oxirane) metabolites formed generally undergo further biotransformation to more polar and readily excreted metabolites via conjugation with glutathione or epoxide-hydrolase-mediated hydrolysis to diols. Thus, epoxidation can be considered the first step in a metabolic detoxification scheme. On the other hand, epoxidation is also a...

Printed In The United States Of America

To my wife, Pamela Zulli my best friend, companion, and constant source of inspiration. In the beginning, medicinal therapy consisted of concoctions coadministered with incantations. Little thought was given to dissecting out the contributions of the pharmacology of the concoction from the spiritual consequences of the incantations. Eventually, potions and extracts were recognized to have predictable activity that could be observed and described objectively. Then came the capacity to estimate...

ROCOC1 KRj ROCONR

Primary and secondary amino groups undergo facile reaction with isocyanates to give the corresponding ureas (Eq, 4), and this transformation has been exploited for the derivatization of amines R-N C 0 + HNR'R RNH-CO-NR'R (4) Two commercially available optically active isocyanates have been extensively used as CDAs in LC 1-phenylethyl isocyanate ( 19 , also known as a-methylbenzyl isocyanate) and l-(l-naphthyl)ethyl isocyanate, 20 . Both enantiomers of each of these CDAs are...

Equipotent Enantiomers

There are not many known racemic drugs with equipotent enantiomers (4). Examples include the antiasthmatic drug proxyphylline, the antineoplastic cyclophosphamide, the antimalarial agent primaquine, and the antiarrhythmic agents propafenone, flecairtide, and disopyramide. For these drugs there seems to be little rationale for separating the two enantiomers, as the known target receptors do not distinguish between the two chemical entities. However, although the enantiomers may be qualitatively...

Stereoselectivity and Toxicity The Rofe of Biotransformation

The prominent role of stereochemical factors in toxicity is clearly seen with chemotherapeutic drugs. The desired toxicity of these compounds (cytostatic effect), as well as undesired toxicity toward nontumor tissue (cytotoxic effect), depends directly on the configuration of the parent drug. For instance, platinum drugs require a cis and not trans configuration to coordinate bifunctionally to DNA, thus inhibiting DNA replication and transcription (Singh and Koropatnick, 1988). The folate...

Monoclonal Antibodies to Soman

With the advent of hybridoma technology, the question arises as to whether, given a racemic immunogen, one would be able to generate hybridomas producing monoclonal antibodies to both isomers with high enantioselectivity. This is supported by the observed enantioselectivity of polyclonal antisera to racemic immunogens discussed earlier and the results obtained with nicotine (67), The selectivity of such antibodies was less clear cut with a diastereoisomeric compound. Monoclonal antibodies were...

Perspectives On The Use Of Stereochemically Pure Drugs

FDA Perspective on the Development of New Stereoisomeric Drugs Chemistry Manufacturing, and Control Issues 365 Wilson H. De Camp 14. Stereochemical Pure Drugs An Overview 375 Fakhreddin Jamali 15. Stereoisomeric Drugs in Therapeutics Clinical Perspectives 385 Darrell R. Abernethy and Habil S. Andrawis 16. Development of Stereoisomeric Drugs An Industrial Perspective 399 Mitchell N. Cayen Darreil R. Ab erne thy, Ph.D., M.D. Professor of Medicine and Director, Program in Clinical...

Resolutions via Derivatization of Carboxyl Groups

Many chiral drug molecules contain the carboxyl group. This functional moiety can also be generated metabolically from other structures via such biotransformations as hydrolysis of esters, oxidation of alkyl groups, alcohols, aldehydes, amines, etc. Of particular interest in recent years has been the stereoselectivity in the action and disposition of a group of nonsteroidal antiinflammatory drugs NSAIDs , for example, ibuprofen, feno-profen, flurbiprofen, etc, 181 . These drugs have the...

Stereoselective Protection Against Toxicity

The antagonism or prevention of toxic effects may also benefit from stereochemical principles. Thus, optically active flavanones have been shown to inhibit the metabolic activation of the carcinogen benzo a pyrene to metabolites that bind covalently to DNA Chae et al., 1992 , Moreover, the enantiomers of 3-O-methylcatechin and catechin have been demonstrated to protect stereo selectively against lipid peroxidation due to paracetamol Devalia et al., 1982 . Alternatively, R-cysteine is utilized...

Types Of Stereoisomers

When molecules composed of the same constituents have the same structural formulas but differ only with respect to the spatial arrangement of certain atoms or groups of atoms, they are defined as stereoisomers. Stereoisomers can be optical isomers or geometrical isomers. Optical isomers are members of a set of stereoisomers, at least two of which are optically active or chiral geometrical isomers are members of a set of stereoisomers that contains no optically active members. If the...

Bsa

Analytical tools, but not applicable to the large-scale preparation of pure enantiomers. Type V CSPs are normally used with an aqueous mobile phase containing a phosphate buffer at pH 7.0. Under these conditions, hydrogen bonding and hydrophobic interactions take place between the protein part of the CSP and the solute. In addition, electrostatic interactions can occur. For example, the isoelectric points of AGP and BSA are 2,7 and 4.7, respectively, and both proteins have a net negative charge...

Warfarin

A method for the determination of both warfarin enantiomers based on enantioselective immunoassay has been reported 45 . Warfarin analogs Fig. 6 containing a 4'-carboxyethyl group as the methyl ester were converted to their diastereoisomeric camphor-sulfonates Fig. 6 12b . These were separated chromatographically. Base-catalyzed hydrolysis then removed the camphor-sulfonyl group to yield the pure enantiomeric warfarin analogs. These were individually conjugated to bovine serum albumin by a...