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Here we got the desired lead compound.Lead optimization. The goal of lead optimization is to deliver a compound suitable for testing in humans by subjecting a given lead to a development process to optimize its properties. If the compound does not undergo lead optimization it may lead to problems in the efficacy pharmacokinetics and safety profiles. Leads are first evaluated visually with Swiss-ADME server to evaluate the ADME properties such as solubility profile, GIT absorption and bioavailability profile. Evaluate the toxicity profile and determine the mutagenicity, carcinogenicity, LD50 value, immunotoxicity in both quantitatively and qualitatively by using Toxicity Estimation Software Tool. Leads are also evaluated for their likelihood to be orally bioavailable using the Lipinski's rules. Lipinski’s rules outline the characteristics of molecules that are likely to be absorbed during oral administration. Lipinski’s rules make no statements about potency, just absorption. Lipinski’s rules do, however, impact lead optimization and efforts to increase potency. The two key criteria are molecular weight and lipophilicity. If molecular weight gets too high, then Lipinski’s rules tells us that absorption may suffer. As we increase molecular weight in a race to boost potency, we do need to be careful to monitor PK properties like membrane permeability to ensure the molecule’s absorption is not impaired. While high lipophilicity often means poor solubility, which can impact absorption. Optimization of drug can involve one or more of the following strategies. Identification of the active part or pharmacophore, functional group optimization, structure activity relationship studies, bioisosteric replacement, design of rigid analogs, Homologation of alkyl chains or alteration of chain branching design of aromatic ring position isomers, alteration of ring size and substitution of an aromatic ring for a saturated one or the converse, alteration of stereochemistry or the design of geometric isomers or stereoisomers, design of fragments of the lead molecule that contained a pharmacophoric group or a bone disconnection. Functional group optimization activity or function may be related to its parts or groups. Tweak the right part or their functional groups and you may avoid a particular distribution pattern and its accompanied side-effects. Bioisosteric is a substituents or groups that have chemical door physical similarities and which produce broadly similar biological properties. These are capable of maintaining similar biological activity by mimicking the spatial arrangement, electronic properties or some other physical chemical property of the molecule or functional group that is critical for the retention of biological activity. Major differences in the pharmacological properties are usually due to the difference in electronic effects of the replacement. Increasing the molecular rigidity of a flexible organic molecule may result in potent biologically active agents that are more specific in terms of its pharmacological effect. This can be done by incorporating the elements of a flexible molecule into a rigid ring system or by introducing a carbon-carbon double or triple bond. Isomers formed from altering the rigidity of a molecule may have differences in their therapeutic and toxicological effects. Lead molecules may be much more structurally complex than what is necessary for its pharmacologic effect. Through bone disconnection strategy, you may obtain fragments of the lead molecule and us arrive with a more simple and accessible compound. Alteration of inter atomic distances the relative positions of atoms in a three-dimensional space is also important for a pharmacophore to bind and interact with its target. Atoms must be present in a certain position and distances from each other to observe pharmacological effects. Altering these distances can produce qualitative and quantitative changes in the compounds actions.