化学原料药开发-异构体的分类 ISOMERS.doc

ISOMERS Definition Isomers are compounds that have the same molecular (empirical) formula, but different structures, and demonstrate physico-chemical and pharmacological differences Classification Structural Isomers Definition Compounds with the same empirical formula, but whose atoms are connected in a different sequence Chain isomers have different branching patterns of carbon chains Position isomers the functional group is located on different carbons in the chain tend to have similar chemical properties Functional group isomers have different types of bonds and hence different functional groups tend to have very different chemical properties Tautomers compounds in which, under differing conditions eg pH, the substituent groupings may alter their position structural isomers that readily convert from one isomeric form to another and hence exist in equilibrium Stereoisomers Definition Compounds which have the same empirical formula and whose atoms are attached in the same sequence, but differ in the spatial arrangement of the atoms Significance may have marked pharmacokinetic and pharmacodynamic differences eg levo-bupivacaine is less cardiotoxic than dextro-bupivacaine, only levo isomer of morphine has opioid activity different 3 dimensional arrangement → different ability to interact with receptors, enzymes and non-specific binding sites isomer-specific ability of a drug to produce a pharmacological effect is evidence supporting the presence of receptors Enantiomers stereoisomers that are non-superimposable mirror images (like left and right hands) contain a chiral centre (an asymmetric carbon with four different groups attached to it) identical physical properties, except the direction in which they rotate polarised light Classification Systems a) Rotation of polarised light to the: left: levorotatory l- (-) right: dextrototatory d- (+) a racemic mixture contains equal amounts of levo and dextro isomers and therefore has no overall rotating ef