739366-20-2 Usage
Description
Anagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved
in Japan in November 2012 for the treatment of patients with Type 2 diabetes
mellitus (T2DM).
Anagliptin (also known asSK-0403) is a treatment for diabetes based on inhibition of DPP-4, an enzyme that is responsible for degradation of glucagon-like peptide 1 (GLP-1), a 30-amino acid peptide that is secreted in response to food intake. GLP-1 stimulates
insulin secretion and inhibits glucagon secretion, which leads to lower
levels of plasma glucose. Following the introduction of the first DPP-4 inhibitor, sitagliptin, in 2006, several members of the gliptin class have been approved worldwide. Anagliptin was discovered from an effort to replace
a metabolically labile isoindoline group from an earlier DPP-4 inhibitor series with a stable bioisostere. Anagliptin is a potent DPP-4 inhibitor, with an IC50=3.8 nM and >10,000-fold selectivity over inhibition of DPP-8 and DPP-9.
Originator
Sanwa Kagaku Kenkyusho (Japan)
Uses
Anagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that suppresses proliferation of vascular smooth muscles and monocyte inflammatory reaction. It also attenuates atherosclerosis in male apolipoprotein E-deficient mice.
Brand name
Suiny
Clinical Use
Anagliptin, which is marketed as Beskoa or Suiny, is a dipeptidyl peptidase–IV (DPP-4) inhibitor
which was approved in September 2012 and launched in November 2012 in Japan for the treatment of
Type II diabetes. The drug was co-developed by three Japanese companies; Kowa, Sanwa Kagaku and
JW pharmaceutical. Anagliptin, which is more selective against several recombinant human proteases by comparison to sitagliptin and vildagliptin, has more than 10,000-fold selectivity over the
structurally homologous DPP-8 and DPP-9 enzymes.
Synthesis
The most likely process-scale synthesis has been published and is depicted in Scheme 3.24
Commercially available (S)-1-(2-chloroacetyl)-pyrrolidine-2-carbonitrile (12) was alkylated with t-butyl
(2-amino-2-methyl-1-propyl)carbamate (13), giving rise to (S)-t-butyl (2-((2-(2-cyanopyrrolidin-1-yl)-2-
oxoethyl)amino)-2-methylpropyl)carbamate (14). This Boc-protected system was subsequently treated
with strong acid to give the ethylene diamine derivative 15 in 96% yield. Activation of 15 with CDI
followed by coupling with commercially available 2-methylpyrazolo[1,5-a] pyrimidine-6-carboxylic
acid (16) gave anagliptin (III) in 90% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 739366-20-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,3,9,3,6 and 6 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 739366-20:
(8*7)+(7*3)+(6*9)+(5*3)+(4*6)+(3*6)+(2*2)+(1*0)=192
192 % 10 = 2
So 739366-20-2 is a valid CAS Registry Number.
739366-20-2Relevant articles and documents
2 - Methyl-pyrazolo [1, 5 - a] pyrimidine - 6 - carboxylic acid derivative and its application
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, (2018/03/24)
The invention discloses a 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative and application thereof. The 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative (I) can be used for synthesizing anagliptin. The compound (I) has high stability, and avoids using expensive reagents and harsh reaction conditions in the anagliptin synthesis process. The compound (I) has the advantages of mild reaction conditions, high reaction yield and stable and controllable quality, is simple to operate, avoids column chromatography, low-temperature reaction and other complex after-treatment processes, greatly lowers the anagliptin preparation cost, and is suitable for industrialized mass preparation. The 2-methylpyrazolo[1,5-a]pyrimidyl-6-carboxylic acid derivative is the compound disclosed as Formula (I).
A method for synthesizing allah Geleg sandbank (by machine translation)
-
, (2016/10/10)
The invention relates to a method for preparing anti-II type diabetes drug allah Geleg sandbank method for the synthesis of bulk drug (Anagliptin). The lack of commercial synthetic allah Geleg sandbank solve the technical problems of the method. Synthetic method comprises the following steps : (1) with vinyl ether and trichloro acetyl chloride as the raw material, passes through the three-step reaction to obtain the aldehyde protected intermediates 4 ; The 3-amino-5-methyl pyrazole condensation for dehydrating and gets pyrazolo pyrimidine mother nucleus; Carboxy b ester hydrolysis to obtain 2-methyl-pyrazolo [1,5-a] pyrimidin 6-carboxylic acid 6 ; (2) to L-proline as a raw material, passes through the methyl esterification, ammoniation, acetylation, Carbonitride reaction to obtain the chiral cyano pyrrolizinone intermediate 11 ; Chiral cyano pyrrolizinone intermediate 11 And diamine fragment 12 In alkaline conditions to obtain intermediate affinity substituted 13 ; Finally, intermediate 13 Under the conditions of the hydrochloric acid removal protection Boc base namely obtain cyanopentanoyl Azolylamine intermediate 14 ; (3) 2-methyl-pyrazolo [1,5-a] pyrimidine-6-carboxylic acid 6 The cyano Azolylamine intermediate 14 The condensation conditions to obtain the bulk drug allah Geleg sandbank coupled. (by machine translation)
AN ADVANTAGEOUS PROCESS FOR PREPARING ANAGLIPTIN AND ITS NOVEL CRYSTALLINE FORM-H
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Page/Page column 16, (2016/12/22)
The present invention discloses the process for preparation of Anagliptin and its novel crystalline form-H.
