Mitiglinide calcium

Base Information

• Chemical Name: Mitiglinide calcium
• CAS No.: 145525-41-3
• Molecular Formula: (C19H24NO3)2^.Ca
• Molecular Weight: 668.88
• Hs Code.: 2942000000
• European Community (EC) Number: 691-325-2,692-046-9
• UNII: P5WOR98G68
• DSSTox Substance ID: DTXSID90872410
• Nikkaji Number: J589.787D
• NCI Thesaurus Code: C132050
• Mol file: 145525-41-3.mol

Synonyms:2-benzyl-3-(hexahydro-2-isoindolinylcarbonyl)propionate;calcium 2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate;KAD 1229;KAD-1229;miti-glinide;mitiglinide;S21403

Chemical Property of Mitiglinide calcium

Chemical Property:

• Appearance/Colour: white to off-white crystalline powder
• Vapor Pressure: 1.27E-11mmHg at 25°C
• Melting Point: 146-148 °C
• Boiling Point: 519.6 °C at 760 mmHg
• Flash Point: 268 °C
• PSA: 102.45000
• Density: 1.175 g/cm³
• LogP: 5.59450
• Storage Temp.: room temp
• Solubility.: DMSO: ≥10mg/mL at warmed to 60°C
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 8
• Exact Mass: 668.3138281
• Heavy Atom Count: 47
• Complexity: 411

Purity/Quality:

99% ^*data from raw suppliers

Mitiglinide Calcium ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CCC2CN(CC2C1)C(=O)CC(CC3=CC=CC=C3)C(=O)[O-].C1CCC2CN(CC2C1)C(=O)CC(CC3=CC=CC=C3)C(=O)[O-].[Ca+2]
• Isomeric SMILES: C1CC[C@H]2CN(C[C@H]2C1)C(=O)C[C@H](CC3=CC=CC=C3)C(=O)[O-].C1CC[C@H]2CN(C[C@H]2C1)C(=O)C[C@H](CC3=CC=CC=C3)C(=O)[O-].[Ca+2]
• Recent ClinicalTrials: Post-marketing Clinical Trial of KAD-1229 in Patients With Type 2 Diabetes Mellitus
• Recent NIPH Clinical Trials: Effect of oral hypoglycemic agent for postprandial hyperglycemia administered two times daily on glycemic control in patients with type 2 diabetes with Mitiglinide / Voglibose combination tablets
• Description: Mitiglinide is the calcium salt form of Mitiglinide, which is a drug for the treatment of type II diabetes. It belongs to the meglitinide class blood glucose-lowering drug. Its mechanism of action is through stimulating the insulin secretion through closing the ATP-sensitive potassium channels in the pancreatic beta-cells. This process leads to depolarization, further stimulating the influx of calcium through the voltage-gated calcium channels. The high intracellular calcium level results in the exocytosis of insulin granules, alleviating the symptoms of type II diabetes. Mitiglinide is a non-sulfonylurea hypoglycemic agent that has been developed and launched in Japan for the treatment of type-2 diabetes. Similar to the sulfonylurea insulinotropic drugs, mitiglinide adopts a U-shaped configuration in which the base of the U contains an amide linkage, and each branch of the U incorporates a hydrophobic side chain. This similarity in conformation suggests that mitiglinide also binds to the sulfonylurea receptor to cause the direct closing of ATP-sensitive potassium channels in pancreatic β-cells; the result is stimulation of insulin secretion. In contrast to typical sulfonylurea agents that frequently cause hypoglycemia due to slowly reversed insulinotropic activity, mitiglinide’s short duration of action should be advantageous in preventing this adverse effect. It also enjoys a rapid onset of insulin release. Mitiglinide can be prepared by several closely related methods, which involve either classical resolution of racemic intermediates, or enantioselective methods, such as, chiral enolate alkylation, and asymmetric hydrogenation with a rhodium or ruthenium-based chiral diphosphine complex. A highly efficient preparative method for mitiglinide involves the diasteroselective alkylation of a chiral acylsultam intermediate that is obtained by the reaction of 3-phenylpropionyl chloride with (-)-camphorsultam. The chiral enolate of the acylsultam is derived by using sodium hexamethyldisilazane as the base, and is subsequently alkylated with tert-butyl bromoacetate to achieve ＞93% diastereomeric purity of the product. Following cleavage of the tert-butyl ester with trifluoroacetic acid, the resultant acid is coupled with (3aR,7aS)octahydro-1H-isoindole, and the camphorsultam chiral auxiliary is removed by saponification to produce the parent acid of mitiglinide in high yield. In vitro, mitiglinide has about a 1000-fold greater affinity for the Kir6.2/SUR1 form of potassium-ATP channels expressed in β-cells (IC50=4nM) than for the Kir6.2/SUR2A or Kir6.2/SUR2B channel types found in cardiac and smooth muscle. In fact, it is significantly less potent in blocking potassium-ATP channels than the prototype sulfonylurea glyburide (IC50=42μM vs. 0.13 μM, respectively); thus, it possesses a more favorable cardiac safety profile. Phase III clinical data demonstrated that mitiglinide significantly improved indices of blood glucose control (postprandial glucose and fasting plasma glucose levels) in a double blind, comparative study. It was also confirmed that the incidence of hypoglycemia, a frequent adverse effect, remained as low as placebo. In another placebo-controlled study involving twenty-two patients with type-2 diabetes, mitiglinide 5mg t.i.d. treatment significantly suppressed postprandial plasma glucose elevations (181 vs. 261mg/dL with placebo), and the daily change in blood glucose level was reduced with no subjective symptoms. No episodes of hypoglycemia or abnormal clinical laboratory parameters were noted. Regarding the pharmacokinetics, a single oral dose (unspecified) of mitiglinide reached its peak plasma concentration of about 0.5 μg/mL at 30 minutes post dose and then steadily declined to about 0.04 μg/mL at 4 h.
• Uses: Mitiglinide Calcium is a blood glucose-lowering drugs, stimulating insulin secretion by closing the ATP-sensitive K+ channels in pancreatic beta-cells