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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All lily of the valley flower In order to view it, please contact the author of the presentation. It involves the study of effects of biologically active compounds on the basis of molecular structures or its physico-chemical properties.
Burger define Bioisosteres as substituent’s or groups that have similar chemical and physical properties and which produce broadly similar biological propert i es. The OH group is replaced by other group having ability desgn undergo H-bonding.
Bioisostere – Wikipedia
Univalent atoms and groups. Views Read Edit View history. Go to Application Have a question? Structural size, shape, H-bonding are important 2. Drug Discovery, Design and Development: 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. Isosreric replacement involving cylic vs noncylic analog: 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.
Lead discovery- Random Screening. 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. Pharmacokinetics lipophilicity, hydrophilicity, p K aH-bonding are important 17 Bioisosterism allows modification of physicochemical parameters: Wiley-VCH,p.
Bioisostere to increase absorption: To overcome this problem, replacement of carboxylic acid with bioisostere which has similar physicochemical properties. Introduction to Lead compound. Method of Lead discovery. 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.
By modifying certain substituents, the pharmacological activity of the chalcone and its toxicity are also modified. 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.
For fine tune of biological activity in order to- -Minimize toxicity -Modify the activity -Alter metabolism -Maximize bioavailability 7.
Size, shape, electronic distribution, lipid solubility, water solubility, p K achemical reactivity, hydrogen bonding Effects of bioisosteric replacement: Isosteric replacement of N for X: Bioisosterism allows modification of physicochemical parameters: Trivalent atom and groups.
Drug act as a Antihistamine. WordPress Embed Customize Embed.
Bioisosteres for polar group: Bioisosteres of some patented compounds can be discovered automatically and used to circumvent Markush structure patent claims.
Bivalent atom or groups. Drug discovery, Design and modification. It has been proposed that key force field features, that is the pharmacophorebe patented instead. Bioisosterismm medicinal chemistrybioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties to another chemical compound.
From Wikipedia, the free encyclopedia. Bioisosterism is used to reduce toxicity, change bioavailabilityor modify the activity of the lead compound, and may alter the metabolism of the lead. 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.
Retrieved 15 Jan Another example are chalcones bioisosteres.