Dapagliflozin
[CAS# 461432-26-8]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: Dapagliflozin
• Synonyms: (1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-D-glucitol
• Molecular Formula: C₂₁H₂₅ClO₆
• Molecular Weight: 408.87
• CAS Registry Number: 461432-26-8
• EC Number: 639-683-0
• SMILES: CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)O)O)Cl

Properties

• Solubility: 30 mg/mL (DMSO)
• Density: 1.349

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H315-H318-H319-H372-H373-H411-H413
• Safety Statements: P260-P264-P264+P265-P270-P273-P280-P301+P317-P302+P352-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Dapagliflozin is a medication used for managing type 2 diabetes mellitus, notable for its novel approach to glucose control. Discovered in the early 2000s and approved by regulatory agencies in the 2010s, dapagliflozin has become a significant tool in diabetes management due to its unique mechanism of action and additional health benefits.

Dapagliflozin belongs to the class of drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 is a protein in the kidneys responsible for reabsorbing glucose from urine back into the bloodstream. Dapagliflozin inhibits this transporter, which reduces the reabsorption of glucose and increases its excretion through urine. This mechanism helps to lower blood glucose levels effectively, offering an alternative to traditional diabetes treatments that primarily focus on insulin or its secretion.

The discovery and development of dapagliflozin were driven by the need for more effective and versatile diabetes treatments. Unlike many other diabetes medications, dapagliflozin works independently of insulin and does not typically cause hypoglycemia (low blood sugar) when used alone. Its glucose-dependent mechanism ensures that glucose is only excreted when blood levels are elevated, making it a safer option for managing blood sugar without risking dangerously low glucose levels.

In addition to its primary role in lowering blood glucose levels, dapagliflozin has shown significant cardiovascular benefits. Clinical studies have demonstrated that dapagliflozin can reduce the risk of hospitalization for heart failure in patients with type 2 diabetes, particularly those with pre-existing heart conditions. This dual action of improving glycemic control while supporting cardiovascular health enhances its value in comprehensive diabetes management.

Dapagliflozin is administered orally, typically in the form of tablets taken once daily. It can be used alone or in combination with other diabetes medications, such as metformin, to achieve better glycemic control. The dosage of dapagliflozin is tailored to individual patient needs and responses to treatment.

Common side effects include urinary tract infections, increased urination, and genital fungal infections, which occur due to elevated glucose levels in the urine. Some patients may also experience dehydration or dizziness. These side effects are generally manageable and occur in a relatively small percentage of patients.

Overall, dapagliflozin represents a significant advancement in the treatment of type 2 diabetes. Its development reflects a growing focus on medications that not only control blood glucose levels but also offer additional benefits such as cardiovascular protection and improved overall health outcomes.

References

2019. Synthesis of Dapagliflozin. Synfacts, 15(8).
DOI: 10.1055/s-0039-1690629

2017. Dapagliflozin synthesis. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results

2018. Efficacy and safety study of Dapagliflozin. Diabetes Care.
DOI: 10.2337/dc18-1087