phenylpropanoic acid/diabetes melitus tipe 2

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Discovery of phenylpropanoic acid derivatives containing polar functionalities as potent and orally bioavailable G protein-coupled receptor 40 agonists for the treatment of type 2 diabetes.

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As part of a program to identify potent GPR40 agonists with drug-like properties suitable for clinical development, the incorporation of polar substituents was explored with the intention of decreasing the lipophilicity of our recently disclosed phenylpropanoic acid derivative 1. This incorporation

Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes.

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We have discovered a novel series of isothiazole-based phenylpropanoic acids as GPR120 agonists. Extensive structure-activity relationship studies led to the discovery of a potent GPR120 agonist 4x, which displayed good EC50 values in both calcium and β-arrestin assays. It also presented good

Exploration of phenylpropanoic acids as agonists of the free fatty acid receptor 4 (FFA4): Identification of an orally efficacious FFA4 agonist.

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The long chain free fatty acid receptor 4 (FFA4/GPR120) has recently been recognized as lipid sensor playing important roles in nutrient sensing and inflammation and thus holds potential as a therapeutic target for type 2 diabetes and metabolic syndrome. To explore the effects of stimulating this

Optimization of GPR40 Agonists for Type 2 Diabetes.

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GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized

3-Phenylpropanoic acid-based phosphotyrosine (pTyr) mimetics: hit evolution to a novel orally active protein tyrosine phosphatase 1B (PTP1B) inhibitor.

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Protein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for type 2 diabetes. Herein, we report the evolution of a previously identified 3-phenylpropanoic acid-based PTP1B inhibitor to an orally active lead compound. A series of 3-phenylpropanoic acid-based PTP1B inhibitors were

Design, synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1.

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Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were

Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARalpha/gamma dual agonists, and X-ray crystallographic studies.

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A new series of alpha-aryl or alpha-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of

Improving metabolic stability with deuterium: The discovery of HWL-066, a potent and long-acting free fatty acid receptor 1 agonists.

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The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the

Synthesis and biological evaluation of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists.

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Free fatty acid receptor 1 (FFA1) is a new potential drug target for the treatment of type 2 diabetes because of its role in amplifying glucose-stimulated insulin secretion in pancreatic β-cell. In the present studies, we identified phenoxyacetic acid derivative (18b) as a potent FFA1 agonist

Discovery of TAK-875: A Potent, Selective, and Orally Bioavailable GPR40 Agonist.

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GPR40, one of the G protein-coupled receptors predominantly expressed in pancreatic β-cells, mediates enhancement of glucose-stimulated insulin secretion by free fatty acids. A potent and selective GPR40 agonist is theorized to be a safe and effective antidiabetic drug with little or no risk of

Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold.

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The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus

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