1-(5-Carboxyindol-1-yl)propan-2-ones as inhibitors of human cytosolic phospholipase A2α: Synthesis and properties of bioisosteric benzimidazole, benzotriazole and indazole analogues

Bovens, Stefanie; Kaptur, Martina; Elfringhoff, Alwine Schulze; Lehr, Matthias

doi:10.1016/j.bmcl.2009.03.019

Cited by 23 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…323 The indole ring of the above inhibitors was replaced by benzimidazole, benzotriazole and indazole rings and the inhibitory activity, the metabolic stability and the water solubility were evaluated. 324 Compound 83 bearing an indazole ring (IC 50 value of 5 nM in the vesicle assay) proved to be the most stable metabolically. Most of the above compounds were also tested for their activity against fatty acid amide hydrolase (FAAH), in order to evaluate their dual inhibitory potency.…”

Section: Cytosolic Phospholipase A2 [Group IV Cpla2]mentioning

confidence: 99%

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

et al. 2011

View full text Add to dashboard Cite

Section: Cytosolic Phospholipase A2 [Group IV Cpla2]mentioning

confidence: 99%

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

et al. 2011

View full text Add to dashboard Cite

“…Replacing a lipophilic scaffold with a more polar scaffold can increase the solubility of the molecule. Replacing an indole scaffold with a more polar benzimidazole scaffold has been shown to increase the solubility of a compound 45. Often toxicity is associated with a property of the central scaffold.…”

Section: Scaffold Hoppingmentioning

confidence: 99%

Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization

Langdon

Ertl

Brown

2010

Molecular Informatics

204

126

View full text Add to dashboard Cite

Bioisosteric replacement and scaffold hopping are twin methods used in drug design to improve the synthetic accessibility, potency and drug like properties of a compound and to move into novel chemical space. Bioisosteric replacement involves swapping functional groups of a molecule with other functional groups that have similar biological properties. Scaffold hopping is the replacement of the core framework of a molecule with another scaffold that will improve the properties of the molecule or to find similar potent compounds that exist in novel chemical space. This review outlines the key concepts, importance and challenges of both methods using examples and comparisons of techniques available for finding bioisosteric replacements and scaffold hops. There are many methods available for bioisosteric replacement and scaffold hopping, all with their own advantages and disadvantages. Drug design projects would benefit from a combination of these methods to retrieve diverse and complimentary results. Continuing progress in these fields will allow further validation of both methods as well as the accumulation of knowledge on bioisosteres and possible scaffold replacements.

show abstract

“…Benzotriazole-6-carboxylic acid 61 displayed good inhibition of cPLA 2 α (IC 50 =0.016µmol/L). The replacement of carboxyl benzotriazole into carboxyl indole ring or carboxyl benzimidazole resulted in decreased inhibitory activities (IC 50 =0.035 and 0.085µmol/L, respectively) [148]. These results suggested that the benzotriazole ring played an important role in enhancing its antiinflammatory ability.…”

Section: Benzotriazole As Other Medicinal Agentsmentioning

confidence: 89%

Recent Development of Benzotriazole-based Medicinal Drugs

Ren¹

2014

Med chem

View full text Add to dashboard Cite

The inhibition of kinases is one of the most important pathways to treat cancers attributing to the significant roles of kinases in cell multiplication [24]. The special structure of benzotriazole derivatives could readily bind with different kinases via multiple non-covalent forces such as hydrogen bonds, coordination, ion-dipole, cation-π, π-π stacking, hydrophobic effect and van der Waals force, thus effectively inhibiting the activity of various kinases including protein kinases CK2 and CHK1, histone deacetylases and focal adhesion kinase and so on.

show abstract

1-(5-Carboxyindol-1-yl)propan-2-ones as inhibitors of human cytosolic phospholipase A2α: Synthesis and properties of bioisosteric benzimidazole, benzotriazole and indazole analogues

Cited by 23 publications

References 19 publications

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization

Recent Development of Benzotriazole-based Medicinal Drugs

Contact Info

Product

Resources

About

1-(5-Carboxyindol-1-yl)propan-2-ones as inhibitors of human cytosolic phospholipase A2α: Synthesis and properties of bioisosteric benzimidazole, benzotriazole and indazole analogues

Cited by 23 publications

References 19 publications

Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Phospholipase A2 Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Bioisosteric Replacement and Scaffold Hopping in Lead Generation and Optimization

Recent Development of Benzotriazole-based Medicinal Drugs

Contact Info

Product

Resources

About

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention

Phospholipase A₂ Enzymes: Physical Structure, Biological Function, Disease Implication, Chemical Inhibition, and Therapeutic Intervention