| Identification | Back Directory | [Name]
Anagliptin | [CAS]
739366-20-2 | [Synonyms]
Suiny
SK-0403
Anagliptin
SUINY;SK-0403
Anagliptin API
(R)-N-(2-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethylamino)-2-methylpropyl)-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
(S)-N-(2-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethylaMino)-2-Methylpropyl)-2-Methylpyrazolo[1,5-a]pyriMidine-6-carboxaMide
N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
N-[2-[[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]aMino]-2-Methylpropyl]-2-Methyl-6-pyrazolo[1,5-a]pyriMidinecarboxaMide
N-[2-[[2-[(2S)-2-Cyano-1-pyrrolidinyl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
Pyrazolo[1,5-a]pyrimidine-6-carboxamide, N-[2-[[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]amino]-2-methylpropyl]-2-methyl- | [Molecular Formula]
C19H25N7O2 | [MDL Number]
MFCD19443729 | [MOL File]
739366-20-2.mol | [Molecular Weight]
383.45 |
| Chemical Properties | Back Directory | [Melting point ]
115 - 119°C | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
Refrigerator | [solubility ]
Chloroform (Slightly), Dichloromethane (Slightly), DMSO (Slightly) | [form ]
Solid | [pka]
12.40±0.46(Predicted) | [color ]
White to Off-White | [InChI]
1S/C19H25N7O2/c1-13-7-16-21-9-14(11-26(16)24-13)18(28)22-12-19(2,3)23-10-17(27)25-6-4-5-15(25)8-20/h7,9,11,15,23H,4-6,10,12H2,1-3H3,(H,22,28)/t15-/m0/s1 | [InChIKey]
LDXYBEHACFJIEL-HNNXBMFYSA-N | [SMILES]
[n]21nc(cc2ncc(c1)C(=O)NCC(NCC(=O)N3[C@@H](CCC3)C#N)(C)C)C |
| Hazard Information | Back Directory | [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. | [Definition]
ChEBI: Anagliptin is an amino acid amide. | [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.
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