| Identification | Back Directory | [Name]
N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide | [CAS]
1245603-92-2 | [Synonyms]
EOS-61370
PF-04937319
PF-04937319 >=98% (HPLC)
Inhibitor,PF-04937319,Hexokinase IV,PF 04937319,PF04937319,Hexokinase D,inhibit,Glucokinase
N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide
N,N-Dimethyl-5-[2-methyl-6-[N-(5-methylpyrazin-2-yl)carbamoyl]-1-benzofuran-4-yloxy]pyrimidine-2-carboxamide
N,N-Dimethyl-5-[[2-methyl-6-[[(5-methyl-2-pyrazinyl)amino]carbonyl]-4-benzofuranyl]oxy]-2-pyrimidinecarboxamide
2-Pyrimidinecarboxamide, N,N-dimethyl-5-[[2-methyl-6-[[(5-methyl-2-pyrazinyl)amino]carbonyl]-4-benzofuranyl]oxy]- | [Molecular Formula]
C22H20N6O4 | [MDL Number]
MFCD26960571 | [MOL File]
1245603-92-2.mol | [Molecular Weight]
432.43 |
| Chemical Properties | Back Directory | [density ]
1.366±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Solid | [pka]
10.41±0.70(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
Nerigliatin (PF-04937319) is a orally active glucokinase activator (GKA) with EC50 value of 154.4 μM. Nerigliatin maintains glucose-lowering efficacy. Nerigliatin causes peripheral nerve degeneration. Nerigliatin can be used in type 2 diabetes research. | [Biological Activity]
PF-04937319 is a glucokinase activator with an EC50 value of 174 nM. PF-04937319 was found to improve glycemic control in adults with type 2 diabetes when used in conjunction with metformin.''PF-04937319unlike other glucokinase activatorsis capable of maintaining lower-glucose levels without it resulting in hypoglycemia. In type II diabetic patients where metformin treatment is inadequatePF-04937319 is capable of maintaining glycemic control within the acceptable risk-benefit profile. | [in vivo]
Nerigliatin (males: 50-1000 mg/kg; females: 10-1000 mg/kg; p.o.; once daily; 1 month) causes axonal degeneration in the peripheral (sciatic) nerve of female rats[4].
Nerigliatin (5-500 mg/kg; p.o.; once daily; 1 month) leads to peripheral nerve degeneration and unscheduled deaths in dogs[4].
| Animal Model: | Sprague-Dawley rats (male and female, 10 weeks of age), beagle dogs (male and female, 8-12 months old)[4] | | Dosage: | Rats-males: 50, 250, 1000 mg/kg; females: 10, 50, 1000 mg/kg (suspended in 1.25% hydroxypropyl cellulose and 0.5% docusate sodium); Dogs-males and females: 5, 50, 500 mg/kg (suspended in 1.25% hydroxypropyl cellulose and 0.5% docusate sodium) | | Administration: | Rats-oral gavage, once daily, 1 month; Dogs-oral gavage, once daily, 1 month | | Result: | Caused axonal degeneration in the peripheral (sciatic) nerve of female rats at 50 and 1000 mg/kg in Sprague- Dawley rats.
Led to peripheral nerve degeneration in some animals at 50 and 500 mg/kg, and 2 unscheduled deaths occurred at 500 mg/kg/day in beagle dogs.
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| [References]
[1] Dzyurkevich MS, et al. Pyridoxine dipharmacophore derivatives as potent glucokinase activators for the treatment of type 2 diabetes mellitus. Sci Rep. 2017 Nov 22;7(1):16072. DOI:10.1038/s41598-017-16405-2
[2] Amin NB, et al. Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9. DOI:10.1111/dom.12474
[3] Sharma R, et al. Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator. Drug Metab Dispos. 2014 Nov;42(11):1926-39. DOI:10.1124/dmd.114.060087
[4] Pettersen JC, et al. The relationship of glucokinase activator-induced hypoglycemia with arteriopathy, neuronal necrosis, and peripheral neuropathy in nonclinical studies. Toxicol Pathol. 2014 Jun;42(4):696-708. DOI:10.1177/0192623314526006 |
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