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Systematic (IUPAC) name
8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3- methyl-1-[(4-methylquinazolin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
Clinical data
Trade names Tradjenta, Trajenta
AHFS/ Consumer Drug Information
MedlinePlus a611036
Licence data EMA:Link, US FDA:link
  • US: B (No risk in non-human studies)
Legal status
Routes of
Pharmacokinetic data
Bioavailability 30% oral
Protein binding 75% to 99% in plasma
CAS Registry Number 668270-12-0 YesY
ATC code A10BH05
PubChem CID: 10096344
ChemSpider 8271879 N
KEGG D09566 YesY
Chemical data
Formula C25H28N8O2
Molecular mass 472.54 g/mol
 N (what is this?)  (verify)

Linagliptin (BI-1356, trade names Tradjenta (US), Trajenta (worldwide)) is a DPP-4 inhibitor developed by Boehringer Ingelheim for treatment of type II diabetes.

Linagliptin (once-daily) was approved by the U.S. Food and Drug Administration (FDA) on 2 May 2011 for treatment of type II diabetes.[1] It is being marketed by Boehringer Ingelheim and Lilly.

Mechanism of action[edit]

Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output. Thus, linagliptin stimulates the release of insulin in a glucose-dependent manner and decreases the levels of glucagon in the circulation.

Clinical trials[edit]

Results in 2010 from a Phase III clinical trial of linagliptin showed that the drug can effectively reduce blood sugar.[2]

Chemical Synthesis[edit]

Starting from commercially available 8-bromo-3-methylxanthine 1 linagliptin was prepared in four steps.[3] As part of a sequential alkylation sequence, xanthine derivative 1 was first N-alkylated with butyn-2-yl bromide in the presence of N,N-diisopropylethylamine followed by a second N-alkylation with (chloromethyl)-4-methylquinazoline 3 in the presence of potassium carbonate to furnish xanthine derivative 4. Subsequent nucleophilic aromatic substitution of the bromide in 4 with (R)-3-Boc-aminopiperidine followed by the Boc deprotection of the primary amine in 6 yielded linagliptin.

synthesis of linagliptin

See also[edit]


  • H. Spreitzer (September 1, 2008). "Neue Wirkstoffe - BI-1356". Österreichische Apothekerzeitung (in German) (18/2008): 918. 
  • Wang, Y, Serradell, N, Rosa, E, Castaner, R (2008). "BI-1356". Drugs of the Future 33 (6): 473–477. doi:10.1358/dof.2008.033.06.1215244. 
  1. ^ "FDA Approves Type 2 Diabetes Drug from Boehringer Ingelheim and Lilly". 3 May 2011. 
  2. ^ "Four Phase III Trials Confirm Benefits of BI’s Oral, Once-Daily Type 2 Diabetes Therapy". Genetic Engineering & Biotechnology News. 28 June 2010. 
  3. ^ "8-(3-(R)-Aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a Highly Potent, Selective, Long-Acting, and Orally Bioavailable DPP-4 Inhibitor for the Treatment of Type 2 Diabetes'". Eckhardt M, Langkopf E, Mark M, Tadayyon M, Thomas L, Nar H, Pfrengle W, Guth B, Lotz R, Sieger P, Fuchs H, Himmelsbach F Journal of Medicinal Chemistry; 2007; 50 pp 6450 - 6453; doi:10.1021/jm701280z

External links[edit]