2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11beta-hydroxysteriod dehydrogenase type 1.

doi:10.1021/JM061214F

Paper

2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11beta-hydroxysteriod dehydrogenase type 1.

Published Jan 5, 2007 · D. Jean, C. Yuan, E. A. Bercot

Journal of medicinal chemistry

Q1 SJR score

45

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1

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Abstract

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11beta-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a Ki of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11beta-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.

Study Snapshot

Trifluoromethyl thiazolone 17 shows potential as a potent, orally efficacious inhibitor of 11beta-hydroxysteroid dehydrogenase type 1, potentially treating metabolic syndrome and type 2 diabetes.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11beta-hydroxysteriod dehydrogenase type 1.

References

Citations

Synthesis, anti-diabetic profiling and molecular docking studies of 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones.

Most of the synthesized compounds possess good anti-diabetic potential, with most showing better results via anti-glycation mode.

Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Pseudothiohydantoin derivatives with lipophilicity values below 5 are promising drug candidates due to favorable absorption, distribution, metabolism, and excretion parameters.

11β-Hydroxysteroid Dehydrogenase Type 1 as a Potential Treatment Target in Cardiovascular Diseases

Selective inhibition of 11-HSD1 may offer a potential treatment target for obesity, metabolic syndrome, and cardiovascular complications.

Novel 2-(Adamantan-1-ylamino)Thiazol-4(5H)-One Derivatives and Their Inhibitory Activity towards 11β-HSD1—Synthesis, Molecular Docking and In Vitro Studies

Novel 2-(adamantan-1-ylamino)thiazol-4(5H)-one derivatives show over 50% inhibition of 11-HSD1 activity, potentially benefiting metabolic diseases like obesity and Cushing's syndrome.

Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies

N-methyl derivatives of 2(methylamino)thiazol4(5H)one are weaker inhibitors of 11HSD1 compared to their allyl analogs, potentially impacting their potential use in treating Cushing's syndrome, metabolic syndrome, and type 2 diabetes.