Isosterism and Bioisosterism – Download as PDF File .pdf), Text File .txt) or read online. Pharmacology. Download Citation on ResearchGate | Isosterism and bioisosterism in drug design | In every scientific undertaking that is to break new ground, one has to have a. Aug 1, Isosterism and bioisosterism in drug design. By Alfred Burger. University of Virginia, Department of Chemistry,. Charlottesville, Virgina

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It involves the study of effects of biologically active compounds on the basis of molecular structures or its physico-chemical properties. Trivalent atom and groups. Bioisosterism is used to reduce toxicity, change bioavailabilityor modify the activity of the lead compound, and may alter the metabolism of the lead.

In drug design[1] the purpose of exchanging one bioisostere for another is to enhance the desired biological or physical properties of a compound without making significant changes in chemical structure.

Tetrazole anaion is 10 times more lipophilic than a carboxylic acid and drug absorption is enhanced as a result 23 Carboxylic acid 5-Substiuted tetrazole H- acidic proton Bioisostere to increase absorption: Isosteric replacement of N for X: For fine tune of biological activity in order to- -Minimize toxicity -Modify the activity -Alter metabolism -Maximize bioavailability 7.

Method of Lead discovery. Optimization of Lead -Identification of the active bioisosteriam. For example, the replacement of a hydrogen atom with a fluorine atom at a site of metabolic oxidation in a drug candidate may prevent such metabolism from taking place. By modifying certain substituents, the pharmacological activity of the chalcone and its toxicity are also modified.


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However, with a blocked pathway for metabolism, the drug candidate may have a longer half-life. Isosteris main use of this term and its techniques are related to pharmaceutical sciences.

Because the fluorine atom is similar in size to the hydrogen atom the overall topology of the molecule is not significantly affected, leaving the desired biological activity unaffected. Size, shape, electronic distribution, lipid solubility, water solubility, p K achemical reactivity, hydrogen bioisoserism Effects of bioisosteric replacement: Bioisosteres in Medicinal Chemistry. Drug discovery, Design and modification.

Go to Application Have a question? Isosteric replacement of S for X: In order to view it, please contact the author of the presentation. Pharmacokinetics lipophilicity, hydrophilicity, p K aH-bonding are important 17 Bioisosterism allows modification of physicochemical parameters: Isosreric replacement involving cylic vs noncylic analog: Whereas classical bioisosteres commonly conserve bioisosteeism of the same structural properties, nonclassical bioisosteres are much more dependent on the specific binding needs of the ligand in question and adn substitute a linear functional group for a cyclic moiety, an alkyl group for a complex heteroatom moiety, or other changes that go far beyond a simple atom-for-atom switch.

Retrieved from ” https: Non classical bioisosteres Do not have same number of atom and do not fit the steric and electronic rules of classical isosteres, but they produce similar biological activity Examples- a. The OH group is replaced by other bioisosterissm having ability to undergo H-bonding.

Why Lead Modification is Necessary?: The lead is prototype compound that has the desired biological or pharmacological activity but may have many undesirable isostdrism high toxicity, other biological activity, insolubility or metabolism problems. Univalent atoms and groups. Drug act as a Antihistamine.



Amrutkar Department of Pharmaceutical Chemistry M. It has been proposed that key force field features, that is the pharmacophorebe patented instead.

Bioisosteres of some patented compounds can be discovered automatically and used to circumvent Markush structure patent claims. All lily of the valley flower Upload from Desktop Single File Upload.

The presentation is successfully added In Your Favorites. This page was last edited on 31 Octoberat Another example are chalcones bioisosteres.

Silafluofen is an organosilicon analogue of pyrethroid insecticidewherein a carbon center has been replaced by isosteric silicon. From Wikipedia, the free encyclopedia. In medicinal chemistrybioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound.

WordPress Embed Customize Embed. Silicon Isosteres in Drug Discovery”. Bivalent atom or groups. Structural size, shape, H-bonding are important 2. Hence alkylsulphonamido derivative of phenylepherine was found to retain activity. Conclusion References 2 PowerPoint Presentation: Application of Bioisosterism in Drug design. By using this site, you agree to the Terms of Use and Privacy Policy.