Alogliptin benzoate
[CAS 850649-62-6]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: Alogliptin benzoate
• Synonyms: 2-[[6-[(3R)-3-Amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]benzonitrile benzoate
• Molecular Formula: C₁₈H₂₁N₅O₂.C₇H₆O₂
• Molecular Weight: 461.52
• CAS Registry Number: 850649-62-6
• EC Number: 691-730-4
• SMILES: CN1C(=O)C=C(N(C1=O)CC2=CC=CC=C2C#N)N3CCC[C@H](C3)N.C1=CC=C(C=C1)C(=O)O

Properties

• Solubility: DMSO: 10 mM (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Risk Statements: H302-H373
• Safety Statements: P260-P264-P270-P301+P317-P319-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	4	H302

chemBlink Chemical Story

Alogliptin benzoate is the benzoate salt form of alogliptin, a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). It is an antidiabetic drug used in the management of type 2 diabetes mellitus by enhancing incretin hormone activity, thereby improving glucose-dependent insulin secretion.

Structurally, alogliptin is a small heterocyclic organic molecule containing a bicyclic core with multiple nitrogen atoms, including a pyrimidinedione-like fragment and a substituted aminopiperidine moiety. The molecule is designed to fit into the active site of the DPP-4 enzyme, where it forms noncovalent interactions that block substrate access. The presence of heteroatoms such as nitrogen and oxygen enables hydrogen bonding and electrostatic interactions with amino acid residues in the enzyme binding pocket.

The benzoate component is a simple aromatic carboxylate derived from benzoic acid. In the salt form, the basic nitrogen center of alogliptin is protonated and paired with a benzoate anion. This ionic pairing improves solid-state stability, crystallinity, and pharmaceutical handling properties compared with the free base.

Alogliptin contains several functional groups that contribute to its biological activity. These include carbonyl groups capable of hydrogen bonding, secondary and tertiary amine functionalities that can be protonated under physiological conditions, and hydrophobic aromatic or alicyclic regions that enhance binding affinity within the largely hydrophobic pockets of the DPP-4 enzyme.

The mechanism of action of alogliptin is based on reversible, competitive inhibition of DPP-4. This enzyme is responsible for the degradation of incretin hormones such as GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). By inhibiting DPP-4, alogliptin increases the half-life of these hormones, leading to enhanced insulin secretion from pancreatic beta cells in response to meals and reduced glucagon secretion from alpha cells.

From a structural biology perspective, alogliptin binds to the catalytic site of DPP-4 through a combination of hydrogen bonding, hydrophobic interactions, and shape complementarity. The enzyme’s active site contains a serine protease catalytic triad, and although alogliptin does not form a covalent bond, it occupies the substrate-binding pocket and prevents access by natural peptide substrates.

Physicochemically, alogliptin benzoate exhibits improved solubility and stability compared with the neutral form of alogliptin. The ionic interaction between the protonated drug molecule and benzoate counterion enhances crystalline packing and allows for consistent pharmaceutical formulation. The compound is moderately polar overall due to the presence of multiple heteroatoms and ionizable functional groups, but it also contains hydrophobic regions that contribute to membrane permeability.

The benzoate ion itself is not pharmacologically active but plays an important role in modulating the drug’s solid-state properties. It can participate in π–π interactions and hydrogen bonding within the crystal lattice, contributing to improved manufacturability and shelf stability.

Chemically, alogliptin is stable under physiological conditions and is not highly reactive. Its functional groups are designed for binding specificity rather than chemical reactivity. Metabolism occurs primarily through limited enzymatic pathways, with the parent compound being the main active form responsible for DPP-4 inhibition.

Overall, alogliptin benzoate is a pharmaceutically optimized salt form of a selective DPP-4 inhibitor. Its structure combines heterocyclic nitrogen-rich motifs with hydrophobic and hydrogen-bonding elements, enabling high-affinity binding to the DPP-4 enzyme and effective modulation of incretin hormone levels for the treatment of type 2 diabetes.

References

2025. Spectrophotometric Methods for Simultaneous Development and Validation of Anti-diabetic drug Alogliptin and Canagliflozin. Journal of Pharmaceutical Innovation.
DOI: 10.1007/s12247-025-10053-0

2025. Development of Alogliptin Oral-Dissolving Films with Optimized Therapeutic Outcomes. Pharmaceutical Research.
DOI: 10.1007/s11095-025-03873-9

2025. A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment. Journal of Pharmacokinetics and Pharmacodynamics.
DOI: 10.1007/s10928-025-09961-y