850649-62-6 Usage
Indications and Usage
Alogliptin (benzoic acid) is a type-2 diabetes medication, and it is a type of serine protease dipeptidyl peptidase IV (DPP-4) inhibitor developed by the Japanese company Takeda. Alogliptin, used alone or in combination with other blood sugar-lowering medication, is usually well-tolerated in type-2 diabetes patients. This medication has a low risk of hypoglycemia, with Alogliptin treatment groups ≤8.3% and placebo groups ≤10.5%, and shows no difference between young and elderly patients. In addition to effectively lowering blood sugar, this medicine also lowers the risks of hypoglycemia and weight increase, overcoming great obstacles in patient treatment and providing new hope for diabetes treatment.
Mechanisms of Action
Alogliptin selectively inhibits DPP-4 to reduce the inactivation of glucagon-like peptide 1 (GLP-1) and increase the GLP-1 levels in the body, thus lowering blood sugar. Once blood sugar reaches normal levels, it will cease its sugar-lowering effects, thus effectively reducing the risks of hypoglycemia. Additionally, DPP-4 inhibitor also slows gastric emptying, increases the feeling of fullness, and controls appetite, thus helping patients control their weight.
Adverse reactions
Common side effects of Alogliptin include nasopharyngitis, headaches, and upper respiratory tract infection. Most side effects are light to moderate and are unrelated to dosage.
Uses
Alogliptin Benzoate is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Alogliptin Benzoate is used in the treatment of type 2 diabetes.
Definition
ChEBI: A benzoate salt obtained by combining equimolar amounts of alogliptin and benzoic acid. Used for treatment of type 2 diabetes.
Biological Activity
alogliptin is a novel, highly selective and potent inhibitor of serine protease dipeptidylpeptidase-4 (dpp-4) with ic50 value of less than 10 nm [1].alogliptin has been reported to significantly reduce plasma dpp-4 activity and increase active glp-1 levels in a dose-dependent manner in ob/ob mice. besides, alogliptin after 4 weeks administration remarkably reduced non-fasting glycosylated hemoglobin, non-fasting plasma glucose and triglyceride levels, as well as siginificantly increased non-fasting plasma insulin and fasting pancreatic insulin content in ob/ob mice. moreover, alogliptin treated ob/ob mice have shown the increase of early-phase insulin secretion and the decrease of plasma glucose auc [2]
Clinical Use
Alogliptin benzoate is a dipeptidyl peptidase IV (DPPIV) inhibitor discovered by Takeda
Pharmaceuticals and approved in Japan in 2010 for the treatment of type II diabetes mellitus.
Alogliptin is an oral drug for once a day dosing to complement diet and exercise. Alogliptin is the most
selective marketed DPPIV inhibition and has similar PK and PD properties compared to previous entries. The discovery, structure-activity relationship of related analogs, and synthesis of this
compound have been recently published.
Synthesis
The most convenient synthesis for scale-up will be
highlighted from several published routes. Commercially available 2-cycanobenzyl
amine 1 was reacted with methylisocyanate in DCM at ambient temperature to provide N-methyl urea 2
in 85% yield. Reaction of the urea 2 with dimethyl malonate in refluxing ethanol with sodium ethoxide
as base gave the cyclized trione 3 in 78-85% yield. The trione 3 was then refluxed in neat POCl3 to
provide the penultimate chloride crude 4 in 95% yield which was reacted with Boc-protected diamine 5
in the presense of potassium carbonate in DMF to furnish alogliptin I in 93-96% yield. Treatment of
alogliptin with benzoic acid in ethanol at 60-70 °C followed by crystallization delivered the desired
alogliptin benzoate (I).
references
[1] feng j, zhang z, wallace mb, stafford ja, kaldor sw, kassel db, navre m, shi l, skene rj, asakawa t, takeuchi k, xu r, webb dr, gwaltney sl 2nd. discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase iv. j med chem. 2007 may 17;50(10):2297-300.[2] moritoh y1, takeuchi k, asakawa t, kataoka o, odaka h. chronic administration of alogliptin, a novel, potent, and highly selective dipeptidyl peptidase-4 inhibitor, improves glycemic control and beta-cell function in obese diabetic ob/ob mice. eur j pharmacol. 2008 jul 7;588(2-3):325-32.
Check Digit Verification of cas no
The CAS Registry Mumber 850649-62-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,5,0,6,4 and 9 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 850649-62:
(8*8)+(7*5)+(6*0)+(5*6)+(4*4)+(3*9)+(2*6)+(1*2)=186
186 % 10 = 6
So 850649-62-6 is a valid CAS Registry Number.
InChI:InChI=1/C18H21N5O2.C7H6O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19;8-7(9)6-4-2-1-3-5-6/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3;1-5H,(H,8,9)/t15-;/m1./s1
850649-62-6Relevant articles and documents
Preparation method of alogliptin benzoate
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, (2021/01/29)
The invention discloses a preparation method of alogliptin benzoate. Main starting materials of the preparation method are 6-chloro-3-methyluracil, o-cyanobenzyl bromide, (R)-3-Boc-aminopiperidine andbenzoic acid. According to the method, all indexes meet the specification, meanwhile, dangerous reagents such as sodium hydride and highly toxic methyl iodide are prevented from being used in the reaction process, the requirement for the operation process is not strict, and water-free and oxygen-free conditions are not needed; a high-boiling-point mixed solvent is not used in the reaction, and the solvent is easy to recycle; the selected starting materials are available in the market and easy to obtain, and large-scale production is facilitated; in addition, starting materials or intermediates in the synthetic route are good in stability and convenient to store and control, and genotoxic impurities are avoided in the reaction process; and the synthesis process is environment-friendly.
Development and Scale-Up of an Asymmetric Synthesis Process for Alogliptin
Yamada, Masatoshi,Hirano, Sayuri,Tsuruoka, Ryoji,Takasuga, Masahiro,Uno, Kenichi,Yamaguchi, Kotaro,Yamano, Mitsuhisa
, p. 327 - 336 (2021/03/01)
Alogliptin (1) benzoate is a potent, highly selective inhibitor of serine protease dipeptidyl-peptidase IV, approved by US FDA for the treatment of type 2 diabetes. Herein, we report a more cost-effective process that includes ruthenium-catalyzed asymmetric hydrogenation followed by Hofmann rearrangement of 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrile (10) to introduce a chiral amino moiety at a late stage. Use of an inexpensive and readily available nicotinamide (6) for a chiral aminopiperidine core and iodobenzene diacetate (PIDA) under mild and specific conditions allowed us to access 1 with excellent total yield and comparable quality to that manufactured by the original process.
Novel preparation process of alogliptin benzoate
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Paragraph 0035; 0038; 0045-0046, (2021/05/08)
The invention discloses a novel preparation process of alogliptin benzoate. The method comprises the steps: reacting 3-methyl-6-chlorouracil serving as an initial raw material with 2-cyanobenzyl bromide under an alkaline condition by taking toluene as a solvent to obtain 2-[(6-chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile, then reacting the solvent system with (R)-3-Boc-aminopiperidine under an alkaline condition, dissociating a protecting group by using acid to obtain alogliptin, and carrying out salifying reaction on the alogliptin and benzoic acid to finally prepare the alogliptin benzoate which is an anti-type 2 diabetes medicine. The preparation method adopts a one-pot method, has the advantages of low raw material cost, high yield, reduction of post-treatment operation of each chemical reaction in multi-step reaction, great shortening of the production period, few impurities generated in the reaction, high product quality, relative reduction of the use amount of chemical reagents, relatively environmental protection and the like, and is beneficial to industrial production.