May 7, Application of Isosteres in Drug Design Oxetanes in Drug Discovery 2) exchangeable group isosterism in which the properties of discrete. Nov 10, strategy for drug design. APPLICATION OF CLASSICAL BIOISOSTERISM IN DRUG DESIGN. Isosterism can also contribute to the productive application in the design and optimization of catalysts on organic chemistry. In every scientific undertaking that is to break new ground, one has to have a goal, a working hypothesis, or a leading idea or fact. This will encourage research.
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Hydroxy group- -OH d.
Drug act as bjoisosterism Antihistamine PowerPoint Presentation: However, with a blocked pathway for metabolism, the drug candidate may have a longer half-life. Bioisostere increase target interaction and selectivity: Another example is aromatic rings, a phenyl -C 6 H 5 ring can often be replaced by a different aromatic ring such as thiophene or naphthalene which may improve efficacy, change specificity of isosteriwm, or reduce metabolically labile sites on the molecule, resulting in better pharmacokinetic properties.
Bioisosteres of some patented compounds can be discovered automatically and used to circumvent Markush structure patent claims. Size, shape, electronic distribution, lipid solubility, water solubility, p K achemical reactivity, hydrogen bonding Effects of bioisosteric replacement: Promising Starting Points for Drug Design”. Replacement of Methyl by Chlorine: WordPress Embed Customize Bioisosterismm.
To overcome this problem, replacement of carboxylic bioisostfrism with bioisostere which has similar physicochemical properties. Isosreric replacement involving cylic vs noncylic analog: Isosteric replacement of S for X: Trivalent atom and groups. Structural size, shape, H-bonding are important 2.
Retrieved 15 Jan For fine tune of biological activity in order to- -Minimize toxicity -Modify the activity -Alter metabolism -Maximize bioavailability 7 PowerPoint Presentation: Hence alkylsulphonamido derivative of phenylepherine was found to retain activity.
Go to Application Have a question? Application of Bioisosterism in Drug design. Catechol- 16 PowerPoint Presentation: Drug discovery, Design and modification. All lily of the valley flower 13 Why Bioisosterism?
Classical bioisosterism was originally formulated by James Moir and refined by Irving Langmuir  as a response to the observation that different atoms with the same valence electron structure had similar biological properties.
Alferrd Burger Bioisosteric Replacement. Isosteric Replacement of Si for C: Automatically changes to Flash or non-Flash embed. Pharm Dtug — Sem. Drug act as a Antihistamine. Alpha tocopherol —reduce cardiac damage due to myocardial infraction.
In drug design 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. Upload from Desiggn Single File Upload. The lead is prototype compound that has the desired biological or pharmacological activity but may have many undesirable characterisics,like high toxicity, other biological activity, insolubility or metabolism problems.
It has been proposed that key force field features, that is the pharmacophorebe patented instead. Non-classical bioisosteres may differ in a multitude of ways from classical bioisosteres, but retain the focus on providing similar sterics and electronic profile to the original functional group.
Why Lead Modification is Necessary?: Views Read Edit View history. 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 group having ability to undergo H-bonding. In medicinal chemistrybioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound.
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. Optimization of Lead -Identification of the active part. Bioisosterism allows modification of physicochemical parameters: Amrutkar Department of Pharmaceutical Chemistry M.
In order to view it, please contact the author of the presentation. Bivalent atom or groups. Bioisosteres in Medicinal Chemistry. Whereas classical bioisosteres commonly conserve much of the same structural properties, nonclassical bioisosteres are much more dependent on the specific binding needs of the ligand in question and may 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.
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: The main use of this term and its techniques are related to pharmaceutical sciences.
Another example are chalcones bioisosteres. You do not have the permission to view this presentation. By modifying certain substituents, the pharmacological activity of the chalcone and its toxicity are also modified. It involves the study of effects of biologically active compounds on the basis of molecular structures or its physico-chemical properties.
Silicon Isosteres in Drug Discovery”.