850649-61-5 Usage
Description
Alogliptin is a dipeptidyl-peptidase IV (DPP-4) inhibitor that was
approved in Japan in 2010 for treatment of type 2 diabetes, a disease in
which insulin resistance and β-cell dysfunction lead to hyperglycemia.
As islet function is lost, the severity of insulin resistance
increases. The introduction of DPP-4 inhibitors has brought a novel
class of insulinotropic agents for the treatment options available to type
2 diabetic patients. The therapeutic potential of glucagon-like peptide 1
(GLP-1), an incretin peptide, for the treatment of type 2 diabetes was
realized in the 1990s. The insulinotropic effects of GLP-1 depend closely
on glucose concentrations providing the possibility of glucose normalization
without the risk of hypoglycemia. GLP-1 has other non-insulinotropic
physiological actions that are advantageous. It suppresses glucagon
secretion from a cells and slows gastric emptying, which contributes to
satiety and to a slower passage and reabsorption of carbohydrates. GLP-1
also contributes to satiety via a central mechanism as a neurotransmitter
with effects on the hypothalamus.
Chemical Properties
White Solid
Originator
Syrrx Inc. (now Takeda San Diego) (Japan)
Uses
Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4).
Antidiabetic agent.
Definition
ChEBI: A piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of t
pe 2 diabetes.
Brand name
Nesina
Clinical Use
Dipeptidyl peptidase 4 inhibitor:
Treatment of type 2 diabetes in combination with
other therapies
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Alogliptin does not undergo extensive metabolism. Two
minor metabolites were detected following administration
of an oral dose of [14C]-alogliptin, N-demethylated
alogliptin, M-I (<1% of the parent compound), and
N-acetylated alogliptin, M-II (<6% of the parent
compound). M-I is an active metabolite and is a highly
selective inhibitor of DPP-4 similar to alogliptin; M-II
does not display any inhibitory activity towards DPP-4
or other DPP-related enzymes. In vitro data indicate
that CYP2D6 and CYP3A4 contribute to the limited
metabolism of alogliptin.
Check Digit Verification of cas no
The CAS Registry Mumber 850649-61-5 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 1 respectively.
Calculate Digit Verification of CAS Registry Number 850649-61:
(8*8)+(7*5)+(6*0)+(5*6)+(4*4)+(3*9)+(2*6)+(1*1)=185
185 % 10 = 5
So 850649-61-5 is a valid CAS Registry Number.
InChI:InChI:1S/C18H21N5O2/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/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3
850649-61-5Relevant articles and documents
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.
Synthesis process of alogliptin benzoate
-
, (2021/02/10)
The invention discloses a synthesis process of alogliptin benzoate. The synthesis process comprises the following steps: 1, preparing an initial raw material 6-chlorouracil; 2, preparing 2-((6-chlorine-2, 4-dioxo-3, 4-dihydro-2H-pyrimidine-1-radical)methyl)cyanophenyl; 3, preparing 2-[(6-chlorine-3, 4-dihydro-3-methyl-2, 4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile; 4, preparing alogliptin; 5, preparing alogliptin benzoate. According to the invention, the alogliptin benzoate is synthesized by taking cheap and easily available 6-chlorouracil, alpha bromo-o-methylbenzonitrile and (R)-3-aminopiperidine as raw materials through reactions such as alkylation, methylation, affinity substitution, salification and the like; according to the synthetic route, raw materials are cheap and easy to obtain, the synthetic cost is reduced, all steps are classic reactions, and synthesis improvement is easy; the improved process is low in raw material cost, simple to operate, mild in reaction condition,simple in post-treatment and suitable for industrial production.
Simple preparation method of alogliptin benzoate
-
Paragraph 0068-0070, (2019/10/01)
The invention relates to an alogliptin benzoate preparation method, which comprises that 3,3-dihalogenated-N-methyl acrylamide sequentially reacts with (R)-3-Boc-aminopiperidine and 2-cyano benzylamine to prepare (R)-3-(3-Bocamino)piperidine-1-yl-3-(2-cyano)benzylamino-N-methacrylamide, the obtained material reacts with a carbonylation reagent to prepare alogliptin, and the alogliptin and benzoicacid are subjected to salt forming to prepare alogliptin benzoate. According to the present invention, the method has advantages of inexpensive and easily available raw materials, simple operation andless wastewater, and is suitable for the industrial production of alogliptin benzoate.