(S)-2-Benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyric Acid Calcium Salt Hydrate
KAD-1229 Calcium Hydrate
CAS: 207844-01-7
Molecular Formula: C38H52CaN2O8
(S)-2-Benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyric Acid Calcium Salt Hydrate - Names and Identifiers
(S)-2-Benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyric Acid Calcium Salt Hydrate - Physico-chemical Properties
| Molecular Formula | C38H52CaN2O8 |
| Molar Mass | 704.91 |
| Melting Point | 179-185°C |
| Solubility | Methanol (Slightly) |
| Appearance | Solid |
| Color | White |
| Storage Condition | Inert atmosphere,Room Temperature |
(S)-2-Benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyric Acid Calcium Salt Hydrate - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 1.415 ml | 7.073 ml | 14.146 ml |
| 5 mM | 0.283 ml | 1.415 ml | 2.829 ml |
| 10 mM | 0.141 ml | 0.707 ml | 1.415 ml |
| 5 mM | 0.028 ml | 0.141 ml | 0.283 ml |
Last Update：2024-01-02 23:10:35
(S)-2-Benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyric Acid Calcium Salt Hydrate - Reference Information
| Introduction | mitiglinide calcium, chemical name (2S)-2-benzyl -3-(cis-hexahydro-2-isoindolylcarbonyl) calcium propionate dihydrate, clinically used for the treatment of type II diabetes. It was developed by Kissei Pharmaceutical Company of Japan and was first listed in Japan in May 2004. |
| mechanism of action | mitiglinide calcium is the third meglitamide after repaglinide and nateglinide, it is an ATP-dependent potassium channel blocker, which is a derivative of phenylalanine. Its mechanism of action is similar to sulfonylurea, but it has faster onset and short half-life, which is beneficial to reducing postprandial blood glucose in diabetic patients, it can also avoid hypoglycemia caused by continuous hypoglycemic, with the name of "In vitro pancreas. |
| indication | improvement of postprandial hyperglycemia in patients with type 2 diabetes mellitus, exercise therapy can not effectively control blood sugar patients or diet, exercise therapy based on the addition of alpha-glucosidase inhibitors still can not effectively control blood sugar patients). |
| preparation | Step 1: preparation of 2-benzylidene succinic acid sodium methoxide (9kg) and methanol (48L) it was put into a 100L reaction kettle, stirred and dissolved, and then put into a 50L High Level Tank . Put dimethyl succinate (20kg) into 200L reaction kettle, heat reflux, rapid drop add sodium methoxide solution of methyl alcohol in high level tank, drip Reflux reaction for 30min, under reflux condition, benzaldehyde (10.9) was added dropwise, and the mixture was stirred under reflux for 3-5H. The reaction of benzaldehyde was completed by HPLC, and 4N NaOH aqueous solution (38L) was added dropwise, reflux reaction 4~6h, cooled to room temperature, with 6N HCl adjusted to PH ≤ 2, solid precipitation, centrifugation, vacuum drying to light yellow solid 19kg, namely Intermediate 1, the yield was 90%. Step 2: preparation of (S)-2-benzylsuccinic acid test 200L autoclave gas tightness, Intermediate 1(19kg), methanol (95L) and containing 5% Ru(OAc)2 [(S)-BINAP] molecular sieve (SBA-15) supported catalyst (0.95, self-made) was put into the reaction kettle, after replacing the air in the reactor with N2, heated to 50 ℃, atmospheric pressure hydrogen 10h, cooling, filtration, filtrate reduced pressure concentration to dryness, the resulting solid was recrystallized from ethyl acetate, vacuum drying to give off-white solid 15.5, namely Intermediate 2, yield 81%, chiral purity 99.5% e.e.. Step 3:2-(S)-benzyl-4-oxo-(cis-perhydrogenated isoindol-2-yl) butanoic acid in a 500L reactor, ethyl acetate (225L), triethylamine (1.8), imidazole (9.8) and intermediate 2(15kg) were added and cooled to -10 °c with stirring, thionyl chloride (17.2) was added dropwise, and stirring was continued at -10 ℃ ~-5 ℃ for 6H. CIS-perhydroisoindole (9kg) was added dropwise, after dropping, the reaction was stirred at room temperature for 18h, 1N hydrochloric acid (150L) was added to the reaction solution and stirred for 1H, then the liquid was separated and the organic layer was washed with water, extract with 1N sodium hydroxide solution (100L × 3), combine the water layer, wash with ethyl acetate (50L), take the water layer with 1N hydrochloric acid to PH = 3, the aqueous layer was extracted with ethyl acetate (100mL × 3), and the combined layers were washed with saturated brine (50L × 3). The organic layer was dried over anhydrous Na2SO4 and filtered, the filtrate was concentrated under reduced pressure to give 19.8 of an oil, I .e., yield of intermediate 3: 87%. Step 4: preparation of mitiglinide calcium intermediate 3(19.8) and anhydrous ethanol (99L) were put into 200L reactor, stirred and dissolved, 2N hydrogen sodium oxide solution (35L) was added, mixed well and fed into the high-level tank in portions. Add 5% calcium chloride aqueous solution (155L) to the 500L reaction kettle, stir, Dropwise add high tank solution, Dropwise vigorously stir and react for 3-5H, centrifuge, the filter cake was pulped with 95% ethanol (99L) weight crystals, centrifuged, and dried under vacuum (50 ° C./0.09MPa) to obtain the target compound I mitiglinide calcium 16.1, yield 73%. |
| glinide hypoglycemic agents | glinide hypoglycemic agents have the characteristics of rapid, potent and short-acting, it avoids the occurrence of adverse reactions such as hypoglycemia, and has no gastrointestinal adverse reactions of α-glucosidase inhibitors, and is a more competitive postprandial blood glucose regulator. Mitiglinide calcium only in the meal will be rapid and short-term stimulation of pancreatic insulin secretion, rapid onset, short duration of action; Traditional oral diabetes drugs continue to stimulate insulin secretion, and excessive stimulation, especially between meals, often make the patient feel hungry, with sulfonyl pulse drugs even to encourage patients to take snacks between meals, metabolize too much insulin. This extra eating increases the weight of patients who are often obese in the beginning. mitiglinide calcium is the third glinide hypoglycemic drug after repaglinide and nateglinide. It was successfully developed by Kissei and approved by the Ministry of Health and Welfare on November 29, 2004, it was first launched in Japan in May 2004 for the treatment of type 2 diabetes. It is the first-line treatment drug for patients with early and severe type II diabetes, with the name of "In vitro islet. Clinical trials have shown that this class of drugs is so far superior to other hypoglycemic drugs in terms of efficacy and safety. It is a new type of rapid-acting insulin secretion promoting islet cells ", it is suitable for patients with type 2 diabetes who cannot effectively control hyperglycemia by diet and exercise therapy, and is mainly used to control postprandial hyperglycemia. This product can close the K -ATP channel on the islet β cells, increase the intracellular Ca2 concentration and degranulation of the extracellular vesicles containing insulin, thereby stimulating the secretion of insulin. In vitro experiments show that mitiglinide calcium can stimulate insulin secretion of isolated hamster islet cells. Electrophysiological studies show that this product can inhibit the opening of ATP sensitive K channel, at the concentration of 10 mol/L, the channel can be completely blocked, can stimulate Ca2 into cells. In the presence of glucose, mitiglinide calcium can dose-dependently stimulate insulin secretion from isolated and perfused rat pancreas. both mitiglinide and nateglinide are rapid-acting insulin-secreting drugs, but mitiglinide showed more significant improvement in postprandial hyperglycemia. This difference in efficacy is manifested in the effect of mitiglinide on promoting insulin secretion in HIT-T15 cells is about 100 times that of nateglinide, and the effect of promoting insulin secretion in type II diabetic animals is more significant than that of nateglinide. |
| Use | glinides |
Last Update：2024-04-10 22:29:15
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Product Name: Mitiglinide Calcium Salt Dihydrate Request for quotation
CAS: 207844-01-7
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
CAS: 207844-01-7
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: KAD-1229 Calcium Hydrate Visit Supplier Webpage Request for quotationCAS: 207844-01-7
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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