(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile

• ChemBase ID: 4428
• Molecular Formular: C18H25N3O2
• Molecular Mass: 315.41
• Monoisotopic Mass: 315.19467706
• SMILES: OC12CC3(CC(C1)CC(C3)C2)[C@H](N)C(=O)N1[C@@H]2[C@@H](C2)C[C@H]1C#N
• Canonical SMILES: N#C[C@@H]1C[C@H]2[C@@H](N1C(=O)[C@H](C13CC4CC(C1)CC(C3)(C4)O)N)C2
• InChI: InChI=1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
• InChIKey: QGJUIPDUBHWZPV-SGTAVMJGSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
• IUPAC Traditional name: saxagliptin
• Brand Name: Onglyza
• Synonyms: BMS-477118; saxagliptin; Onglyza; Saxagliptin

Database IDs

• CAS Number: 361442-04-8
• PubChem SID: 99443245; 160967860
• PubChem CID: 11243969

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.743205
• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): -2.388905
• LogD (pH = 7.4): -0.6962074
• Log P: -0.079534434
• Molar Refractivity: 83.9913 cm^3
• Polarizability: 33.454536 Å^3
• Polar Surface Area: 90.35 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.88
• LOG S: -2.14
• Solubility (Water): 2.26e+00 g/l

DETAILS

DrugBank - DB06335

• Drug Groups: approved; investigational
• Description: Saxagliptin (rINN), previously identified as BMS-477118, is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. It was developed by Bristol-Myers Squibb. A New Drug Application for saxagliptin in the treatment of type 2 diabetes was submitted to the FDA in June 2008. It was based on a drug development program with 8 randomized trials: 1 phase 2 dose-ranging (2.5–100 mg/d) study; 6 phase 3, 24-week controlled trials with additional controlled follow-up from 12 to 42 months, double-blinded throughout; and one 12-week mechanism-of-action trial with a 2-year follow-up period. In June 2008, it was announced that Onglyza would be the trade name under which saxagliptin will be marketed.
• Indication: Investigated for use/treatment in diabetes mellitus type 2.Z\
• Absorption: Following the 5 mg once daily dose, the median time to maximum concentration is 2 hours.
• Half Life: 2.5 hours
• Elimination: Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.
• Clearance: Renal clearance = 230 mL/min
• References: Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008 May;10(5):376-86. Epub 2008 Mar 18. [Pubmed] ; Metzler WJ, Yanchunas J, Weigelt C, Kish K, Klei HE, Xie D, Zhang Y, Corbett M, Tamura JK, He B, Hamann LG, Kirby MS, Marcinkeviciene J: Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci. 2008 Feb;17(2):240-50. [Pubmed] ; Crepaldi G, Carruba M, Comaschi M, Del Prato S, Frajese G, Paolisso G: Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management. J Endocrinol Invest. 2007 Jul-Aug;30(7):610-4. [Pubmed] ; Barnett A: DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov;60(11):1454-70. [Pubmed] ; Kulasa K, Edelman S: Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2010 Oct 21;5:23-37. [Pubmed]
• External Links: Wikipedia

REFERENCES

• Rosenstock J, Sankoh S, List JF: Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab. 2008 May;10(5):376-86. Epub 2008 Mar 18. Pubmed
• Metzler WJ, Yanchunas J, Weigelt C, Kish K, Klei HE, Xie D, Zhang Y, Corbett M, Tamura JK, He B, Hamann LG, Kirby MS, Marcinkeviciene J: Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci. 2008 Feb;17(2):240-50. Pubmed
• Crepaldi G, Carruba M, Comaschi M, Del Prato S, Frajese G, Paolisso G: Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management. J Endocrinol Invest. 2007 Jul-Aug;30(7):610-4. Pubmed
• Barnett A: DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov;60(11):1454-70. Pubmed
• Kulasa K, Edelman S: Saxagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2010 Oct 21;5:23-37. Pubmed