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Sitagliptin phosphate

CAS No.
654671-78-0
Chemical Name:
Sitagliptin phosphate
Synonyms
Sitagliptin Phosphat;3-Amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]-pyrazin-7(8H)-yl)-4-(2,4,5-t;(3R)-3-aMino-1-[3-(trifluoroMethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;SIT-11;CS-1358;sitagpliptin;Sitagliptin, MK 0431;Sitagliptin phosphate;Sitagliptin Phosphatec;Sitagliptin phosphate salt
CBNumber:
CB71179744
Molecular Formula:
C16H15F6N5O.H3PO4
Molecular Weight:
505.31
MDL Number:
MFCD09952339
MOL File:
654671-78-0.mol
Last updated:2024-10-31 18:15:48

Sitagliptin phosphate Properties

Melting point 202-204°C
storage temp. -20°C Freezer
solubility Methanol (Slightly, Heated), Water (Sparingly, Sonicated)
form Solid
color White to Off-White
InChI InChI=1S/C16H15F6N5O.H3O4P/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22;1-5(2,3)4/h4,6,9H,1-3,5,7,23H2;(H3,1,2,3,4)
InChIKey IQFYVLUXQXSJJN-UHFFFAOYSA-N
SMILES C(C1=CC(F)=C(F)C=C1F)C(N)CC(=O)N1CCN2C(C(F)(F)F)=NN=C2C1.P(O)(O)(O)=O
FDA UNII 494P4635I6

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
GHS07
Signal word  Warning
Hazard statements  H302-H315-H319-H335
Precautionary statements  P261-P305+P351+P338
NFPA 704
0
2 0

Sitagliptin phosphate price More Price(18)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Cayman Chemical 13252 Sitagliptin (phosphate) ≥98% 654671-78-0 50mg $37 2024-03-01 Buy
Cayman Chemical 13252 Sitagliptin (phosphate) ≥98% 654671-78-0 1g $353 2024-03-01 Buy
Cayman Chemical 13252 Sitagliptin (phosphate) ≥98% 654671-78-0 100mg $62 2024-03-01 Buy
Cayman Chemical 13252 Sitagliptin (phosphate) ≥98% 654671-78-0 250mg $127 2024-03-01 Buy
Tocris 6816 Sitagliptin Phosphate ≥98%(HPLC) 654671-78-0 50 $390 2021-12-16 Buy
Product number Packaging Price Buy
13252 50mg $37 Buy
13252 1g $353 Buy
13252 100mg $62 Buy
13252 250mg $127 Buy
6816 50 $390 Buy

Sitagliptin phosphate Chemical Properties,Uses,Production

New antidiabetic drug

Sitagliptin phosphate is dipeptidyl peptidase Ⅳ(DDP-4) inhibitor class of drugs developed by the German Merck company and firstly obtained the US Food and Drug Administration approval for the treatment of type 2 diabetes, is a new antidiabetic drug, can improve the body's own ability to reduce high blood glucose levels, and the relatively increase naturally occurring incretin by inhibiting the activity of this enzyme, including the levels of glucagon-like peptide 1 and glucose-dependent insulinotropic peptide, thereby triggering the pancreas to improve insulin production and stop glucose production in liver, and ultimately reduce the clinical effect of blood glucose concentration. Features of this product is to stimulate insulin secretion, at the same time can alleviate hunger, but does not make weight gain, and also cannot happen hypoglycemia and edema, is not suitable for use in diabetic patients with poor glycemic control and often developed hypoglycemia. By verification of clinical 552 cases of mild to moderate type 2 diabetes, taken once a day Sitagliptin phosphate, once time 100 mg, after taking the drug for 12 weeks, can make glycated hemoglobin reduce 0.6%-1.1%. Incidence of adverse reactions is similar to placebo, the most frequently reported adverse reactions (incidence> 5% and greater than placebo) is a stuffy or runny nose, and sore throat, upper respiratory tract infection and headache.
Clinical studies showed that the Sitagliptin phosphate as monotherapy in patients with type 2 diabetes, can make glycated hemoglobin (HbA1c) levels significantly reduce. When in combination with the metformin or TZDs, has a significant role of adjuvant therapy, can focus on three kinds of major defect in type 2 diabetes: insulin resistance, β-cell dysfunction (reduction of insulin release), and α-cell dysfunction (unsuppressed hepatic glucose generation) plays a role. But the drug should not be used for treatment of patients with type 1 diabetes or diabetic ketoacidosis.
The above information is edited by the chemicalbook of Liu Yujie.

DPP-4 inhibitors

Sitagliptin phosphate (trade name Januvia) is the DPP-4 inhibitor first clinically approved for the treatment of type 2 diabetes, developed by Germany company Merck, and was listed in 2006 in Mexico and the United States in 2007, also obtained EU approval for the treatment of type 2 diabetes. China approval was soon, currently Sitagliptin phosphate tablets has become the second largest drug of oral diabetes drugs in US.
Sitagliptin phosphate can enhance a called incretin system of human physiological system, resulting in physiological hypoglycemic effect. This physiological system itself can affect β cells and α cells of the islet, help to regulate glucose, and insulin reduction only caused by β-cell dysfunction can cause the increase of blood glucose, or because cells α and β-cell dysfunction cause loss of control in hepatic glucose synthesis and thus lead to elevated blood glucose, DPP-4 will produce efficacy.
Sitagliptin phosphate exists dependent of glucose levels, it will not only know hypoglycemic blindly, not predatorily press islet, exhaust the pancreas function. In contrast, the test proved that it has the prospect of long-term protection of human β cells. In addition, it does not lead to side effects such as weight gain, decreased blood glucose, medication compliance of patient will be greatly enhanced. Therefore, in theory it's effective role in life will greatly exceed the current oral antidiabetic drug, insulin dependent of patients will be greatly delayed.

Description

Sitagliptin is the first novel dipeptidyl peptidase IV inhibitor from Merck for the treatment of type 2 diabetes without weight gain and the incidence of hypoglycemia was similar to placebo. Sitagliptin acts by enhancing the body’s incretin system, which helps to regulate glucose by affecting β and α cells in the pancreas.

Chemical Properties

White Solid

Uses

A trizolopyrazine dipeptidyl peptidase IV inhibitor. It has recently been approved for the therapy of type II diabetes.

Uses

Sitagliptin is a trizolopyrazine dipeptidyl peptidase IV inhibitor. Sitagliptin has recently been approved for the therapy of type II diabetes.

General Description

Sitagliptin phosphate is the 1:1 phosphoric acid salt ofsitagliptin free base (i.e., (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)-2-butanamine), and is marketed(Junuvia, 2006) in 25-, 50-, and 100-mg tablets. Acombination product with metformin (Janumet, 2007) intwo strengths (50 mg/500 mg and 50 mg/1,000 mgsitagliptin/metformin) is also available, and sitagliptin mayalso be prescribed with a thiazolidinedione, or possibly a sulfonylurea.The phosphate salt provides very high water solubility.The bioavailability of orally administered sitagliptinis~87%. The drug exhibits relatively low plasma protein binding (~38%), a relatively large volume of distribution(198 L), and a terminal elimination half-life of 12 hours.About 79% of a 100-mg oral dose is excreted unchanged inurine, the balance as trace-level metabolites (CYP3A4, lessercontribution by CYP2C8) in urine or feces: 87% of administeredradioactivity is excreted in urine, and 13% in feces.Active tubular excretion is reported to play a key role in renalclearance of unchanged drug, and may be mediated at least inpart via the organic anion transporter hOAT-3.

Synthesis

Synthesis of sitagliptin started with the slow addition of chloropyrazine (75) to 35% aqueous hydrazine at 60-65??C, controlling this exothermic reaction and making it process-friendly, and the resulting crude pyrazinyl hydrazine was acetylated with trifluoroacetic anhydride to afford bis-trifluoromethylhydrazide 76 in 49% yield from the chloropyrazine. Compound 76 was treated with superphosphoric acid, a diluted form of polyphosphoric acid, to give cyclized compound 77 which was hydrogenated with Pd/C and the resulting product was treated with HCl in IPA to afford compound 78 as its HCl salt in 51% yield from 76. Compound 78 was used later on in a coupling reaction to generate sitagliptin. Compound 79, a beta-ketoester, was subjected to asymmetric reduction with (S)-BinapRuCl2-triethylamine complex in methanol at 80??C, catalytic amount of hydrogen bromide, and 90 psi of hydrogen atmosphere to give the desired beta-hydroxy ester which was hydrolyzed to give carboxylic acid 80 in 94% e.e. and 83% yield. The carboxylic acid 80 was coupled with BnONH2-HCl in the presence of EDC and lithium hydroxide in THF/H2O to give coupled compound 81 which was cyclized to compound 82 with DIAD and triphenylphosphine in THF in 81% yield from compound 80. Compound 82 was then hydrolyzed to |?-amino acid 83 with lithium hydroxide, and the acid was coupled with compound 78 at 0??C with EDC-HCl and NMM as base to give compound 84 in excellent yield. Compound 84 was hydrogenated with 10% Pd/C in an ethanol/H2O mix solvent system. The water was crucial to complete the reaction and restore catalyst activity. Finally, the ethanol solution of the hydrogenated product was treated with phosphoric acid, and sitagliptin (XI) was crystallized as its anhydrous phosphoric acid salt from aqueous ethanol solution.

Synthesis_654671-78-0

in vitro

sitagliptin was a potent inhibitor for dpp-4 with an ic50 of 18 nm [1]. sitagliptin inhibited dpp-8 with an ic50 of 48 μm. sitagliptin showed no effect on several related peptidases, including dpp-9, dpp-ii, and amino peptidase p [1].

storage

Desiccate at RT

References

[1] biftu t, feng d, qian x, et al. (3r)-4-[(3r)-3-amino-4-(2, 4, 5-trifluorophenyl) butanoyl]-3-(2, 2, 2-trifluoroethyl)-1, 4-diazepan-2-one, a selective dipeptidyl peptidase iv inhibitor for the treatment of type 2 diabetes[j]. bioorganic & medicinal chemistry letters, 2007, 17(1): 49-52.
[2] fleischer b. cd26: a surface protease involved in t-cell activation[j]. immunology today, 1994, 15(4): 180-184.
[3] aschner p, kipnes m s, lunceford j k, et al. effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes[j]. diabetes care, 2006, 29(12): 2632-2637.
[4] green j b, bethel m a, armstrong p w, et al. effect of sitagliptin on cardiovascular outcomes in type 2 diabetes[j]. new england journal of medicine, 2015, 373(3): 232-242.

Sitagliptin phosphate Preparation Products And Raw materials

Raw materials

Preparation Products

Global( 361)Suppliers
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Shanghai Jinhuan Chemical CO.,LTD.
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View Lastest Price from Sitagliptin phosphate manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Sitagliptin phosphate pictures 2024-10-31 Sitagliptin phosphate
654671-78-0
US $33.00-57.00 / mg 99.72% 10g TargetMol Chemicals Inc.
Sitagliptin Phosphate pictures 2024-10-31 Sitagliptin Phosphate
654671-78-0
US $0.00 / Kg/Bag 2Kg/Bag 99% up, High Density 20 tons Sinoway Industrial co., ltd.
Sitagliptin Phosphate pictures 2024-10-16 Sitagliptin Phosphate
654671-78-0
US $0.00 / g 1g More Than 99% 50kg/Month BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.

Sitagliptin phosphate Spectrum

7-[(3R)-3-Amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-α]pyrazine-phosphate Sitagliptin phosphate 4-Oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine phosphate sitagpliptin Sitagliptin phosphate 4-Oxo-4-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine phosphate Sitagliptin phosphate/Sitagliptin phosphate Monohydrate/Sitagliptin Sitagliptin phosphate (Cas:654671-78-0... (3R)-3-Amino-1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)-1-butanone phosphate 1-Butanone, 3-amino-1-[5,6-dihydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)-, (3R)-, phosphate (1:1) Sitagliptin, MK 0431 CS-1358 Sitagliptin phosphate salt 99% Sitagliptin Phosphate? Sitagliptin phosphate USP/EP/BP Sitagliptin phosphate (API) Sitagliptin PhosphateQ: What is Sitagliptin Phosphate Q: What is the CAS Number of Sitagliptin Phosphate Q: What is the storage condition of Sitagliptin Phosphate Sitagliptin Phosphatec 3-Amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]-pyrazin-7(8H)-yl)-4-(2,4,5-t (3R)-3-aMino-1-[3-(trifluoroMethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one Sitagliptin Phosphat SIT-11 Sitagliptin Phosphate (Monohydrate and Anhydrous) Sitagliptin Impurity 14 Phosphate Siagliptin phosphate monohydrate Sitagliptin Impurity 19 Phosphate 654671-78-0 C16H15F6N5OH3O4P C16H15F6N5OH3PO4 API Intermediates & Fine Chemicals Pharmaceuticals Pharmaceutical intermdiate All Inhibitors Inhibitors 654671-78-0