Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties
Lead optimization represents the tedious process of fine-tuning lead compounds from biologically active hits to suitable drug candidates for clinical trials. By chemically modifying a hit structure, an improved compound can be obtained in terms of activity, selectivity, and pharmacokinetic ADME (abs...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2022/2164558 |
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| _version_ | 1832553647955771392 |
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| author | Kato Bredael Silke Geurs Dorien Clarisse Karolien De Bosscher Matthias D’hooghe |
| author_facet | Kato Bredael Silke Geurs Dorien Clarisse Karolien De Bosscher Matthias D’hooghe |
| author_sort | Kato Bredael |
| collection | DOAJ |
| description | Lead optimization represents the tedious process of fine-tuning lead compounds from biologically active hits to suitable drug candidates for clinical trials. By chemically modifying a hit structure, an improved compound can be obtained in terms of activity, selectivity, and pharmacokinetic ADME (absorption, distribution, metabolism, and excretion) properties. The carboxylic acid moiety is known to be a crucial functionality in many pharmaceutically active compounds. Despite its common use as a key functionality in drugs, its presence in a lead molecule is often associated with poor pharmacokinetic properties and toxicity. In this literature overview, we discuss how the shortcomings of a carboxylic acid can be circumvented by replacing this functionality with bioisosteres. In this way, the positive aspects of this moiety, such as its activity, for example, by virtue of its capacity to form hydrogen bonds, can be maintained or even improved. To that end, we provide an overview of the most promising carboxylic acid bioisosteres and discuss a selection of synthetic routes towards the main functionalities. |
| format | Article |
| id | doaj-art-eb869c0ebaac4e67ad6db4ac4c90d702 |
| institution | Kabale University |
| issn | 2090-9071 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-eb869c0ebaac4e67ad6db4ac4c90d7022025-02-03T05:53:34ZengWileyJournal of Chemistry2090-90712022-01-01202210.1155/2022/2164558Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and PropertiesKato Bredael0Silke Geurs1Dorien Clarisse2Karolien De Bosscher3Matthias D’hooghe4SynBioC Research GroupSynBioC Research GroupTranslational Nuclear Receptor ResearchTranslational Nuclear Receptor ResearchSynBioC Research GroupLead optimization represents the tedious process of fine-tuning lead compounds from biologically active hits to suitable drug candidates for clinical trials. By chemically modifying a hit structure, an improved compound can be obtained in terms of activity, selectivity, and pharmacokinetic ADME (absorption, distribution, metabolism, and excretion) properties. The carboxylic acid moiety is known to be a crucial functionality in many pharmaceutically active compounds. Despite its common use as a key functionality in drugs, its presence in a lead molecule is often associated with poor pharmacokinetic properties and toxicity. In this literature overview, we discuss how the shortcomings of a carboxylic acid can be circumvented by replacing this functionality with bioisosteres. In this way, the positive aspects of this moiety, such as its activity, for example, by virtue of its capacity to form hydrogen bonds, can be maintained or even improved. To that end, we provide an overview of the most promising carboxylic acid bioisosteres and discuss a selection of synthetic routes towards the main functionalities.http://dx.doi.org/10.1155/2022/2164558 |
| spellingShingle | Kato Bredael Silke Geurs Dorien Clarisse Karolien De Bosscher Matthias D’hooghe Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties Journal of Chemistry |
| title | Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties |
| title_full | Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties |
| title_fullStr | Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties |
| title_full_unstemmed | Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties |
| title_short | Carboxylic Acid Bioisosteres in Medicinal Chemistry: Synthesis and Properties |
| title_sort | carboxylic acid bioisosteres in medicinal chemistry synthesis and properties |
| url | http://dx.doi.org/10.1155/2022/2164558 |
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