1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.

doi:10.1021/JM030091L

Paper

1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.

Published May 24, 2003 · E. B. Villhauer, J. Brinkman, Goli B Naderi

Journal of medicinal chemistry

Q1 SJR score

587

Citations

15

Influential Citations

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Abstract

Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2-[5-cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine (NVP-DPP728, 8c) to its follow-up, 1-[[(3-hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP-LAF237, 12j). The pharmacological profile of 12j in obese Zucker fa/fa rats along with pharmacokinetic profile comparison of 8c and 12j in normal cynomolgus monkeys is discussed. The results suggest that 12j is a potent, stable, selective DPP-IV inhibitor possessing excellent oral bioavailability and potent antihyperglycemic activity with potential for once-a-day administration.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

12j is a potent, selective, and orally bioavailable DPP-IV inhibitor with potential for once-a-day administration for type 2 diabetes treatment.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.

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References

Citations

Greenness assessment for the control of trace-level genotoxic process impurities in Vildagliptin by liquid chromatography with mass spectrometry

The developed method effectively controls trace-level genotoxic impurities in Vildagliptin, with a greenness assessment of 70 and 0.62, respectively.

Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits

Stimulating Gs signaling in enteroendocrine K cells significantly improves glucose homeostasis in obese mice and type 2 diabetes mice, suggesting potential therapeutic applications for diabetes and related metabolic diseases.

Progress in the Stereoselective Synthesis Methods of Pyrrolidine-Containing Drugs and Their Precursors

Stereoselective synthesis methods show promising potential for synthesis of biologically active compounds containing a pyrrolidine ring, with potential applications in drug discovery.

An efficient green synthesis and in vitro evaluation of novel adamantane-containing 4-thiazolidinone derivatives as anticancer agents

Novel 4-thiazolidinone derivatives incorporating an adamantane moiety show promising potential for developing anticancer therapeutics.

Fragment-based QSAR study to explore the structural requirements of DPP-4 inhibitors: a stepping stone towards better type 2 diabetes mellitus management.

Fragment-based QSAR studies can help understand the structural requirements of DPP-4 inhibitors, potentially improving type 2 diabetes management.

Covalent drug – An emerging framework for targeted drug development

Covalent drugs show promise for drug discovery, targeting various proteins and offering heightened selectivity, lower doses, and the degradation of previously undruggable proteins, potentially improving treatment options.

Comparative Binding Study of Gliptins to Bacterial DPP4-like Enzymes for the Treatment of Type 2 Diabetes Mellitus (T2DM)

Gliptins show binding similarities to bacterial DPP4 homologs, suggesting potential interactions with gut microbiota in type 2 diabetes treatment.

Synthesis and clinical application of representative small-molecule dipeptidyl Peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus (T2DM).

Small-molecule DPP-4 inhibitors show promise in treating type 2 diabetes by increasing active glucagon-like peptide-1 (GLP-1), leading to improved insulin secretion and reduced glucagon release.