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Reviews

Acid Isosteres – Acidic Bioisosteres

Di: Everly

Based on the importance of acid isosteres to the field of medicinal chemistry and the critical role that these fragments can play in tuning the properties of acidic, biologically active compounds,

Tetrazoles as carboxylic acid isosteres: chemistry and biology ...

Several carboxylic acid isosteres have been reported, however, the outcome of any isosteric replacement cannot be readily predicted as this strategy is generally found to be

1.6: Drug Modifications to Improve Stability

The extremely detailed “Structure Property Relationships of Carboxylic Acid Isosteres” by Ballatore et. al. provides general trends for the effect a bioisostere will have on membrane

The design of bioisosteres represents a creative and productive approach to improve a molecule, including by enhancing potency, addressing pharmacokinetic challenges, reducing off-target liabilities, and productively

Review Definitions and parameters for determination of (bio)isosterism. We will distinguish between geometric isosteres and bioisosteres. Scaffolds suggested for the

The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational

  • Drug Design: Influence of Heterocyclic Structure as Bioisosteres
  • Tetrazoles as carboxylic acid isosteres: chemistry and biology
  • 药物设计中的羧酸（生物）电子等排体,ChemMedChem

羧酸官能团可以是药效基团的重要组成部分，然而，该部分的存在也可能导致显着的缺点，包括代谢不稳定、毒性以及跨生物膜的被动扩散有限。为了避免其中一些缺点，同时保留羧酸部分的

5-Substituted-1H-tetrazoles (RCN4H) are often used as metabolism-resistant isosteric replacements for carboxylic acids (RCO2H) in SAR-driven medicinal chemistry analogue

The medicinal chemist toolbox is plenty of (bio)isosteres when looking for a carboxylic acid replacement. However, systematic assessment of acid surrogates is often time

The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio)isosteres and to present representative examples demonstrating

Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole,

X = OH, Folic acid N H O N OH N H NH N NH 2 more stable more stable N N H X CO2Et Me MeO2C Dihydropyrimidine calcium channel blockers S 1.85 17 NH 1.50 160 O 1.40 140 IC 50

Carboxylic acids are key pharmacophoric elements in many molecules. They can be seen as a problem by some, due to perceived permeability challenges, potential for high

Commonly employed phosphate bioisosteres can be classified as phosphorus-, carboxylate-, or sulfur-based and squaric acid and squaramide-based isosteres. Table 1

  • Amide Bond Bioisosteres: Strategies, Synthesis, and Successes
  • 1.6: Drug Modifications to Improve Stability
  • Structure Property Relationships of Carboxylic Acid Isosteres
  • Bioisosteres that influence metabolism
  • Carboxylic acid isosteres in drug design

Improving ADME properties is a fundamental aspect of medicinal chemistry to limit the effects of first-pass metabolism while maximizing the efficacy of a drug candidate for its target. The

Herein we report the structure–property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres.

Langmuir introduced the concept of „isosteres“ (or „comolecules“) In the example below, the carboxylic group of glutamic acid was replaced by a 3-hydroxy-5-methyl-4-isoxazole

Herein we report the structure−property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres.

Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres.

the 5-phenyltetrazolic acids and para-electron donating substituent have the reverse effect and is in agreement with substituent effects in benzoic acids. However, the well known acid

The presence of an acidic functionality that can be fully ionized at physiological pH is a key interaction and studies have shown that this engages two arginine residues. A recent

Compared to carboxylic acid, the CX Log P values (www.chemaxon.com) obtained from ChEMBL estimate a variation of + 0.68 and a decrease -0.27 for the τ- and π

acid isosteres for which there is evidence of successful applications in drug design.4 These examples were chosen to represent as wide a range of carboxylic acid surrogates as possible

Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres.

As shown in Fig. 2 and in Supporting Information, when plotting the Δ values of model compounds 3–10 vs previously described phenylpropionic acid derivatives bearing

The goal of this Minireview is to provide an overview of the most commonly employed carboxylic acid (bio)isosteres and to present representative examples demonstrating

Herein we report the structure–property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres.

Isosteres of carboxylic acid have been studied extensively. These studies have typically focused on • enhancing potency • reducing polarity • increasing lipophilicity (improve membrane

In Part 1 of our bioisosteres series, we delve into the critical role of carboxylic acid and amide bioisosteres—two extensively studied functional groups in drug design.