N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine
[CAS 808118-40-3]

Identification

• Classification: Biochemical >> Inhibitor >> Angiogenesis >> HIF inhibitor
• Name: N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine
• Synonyms: [[(4-Hydroxy-1-methyl-7-phenoxyisoquinolin-3-yl)carbonyl]amino]acetic acid
• Molecular Formula: C₁₉H₁₆N₂O₅
• Molecular Weight: 352.34
• CAS Registry Number: 808118-40-3
• EC Number: 813-400-2
• SMILES: CC1=C2C=C(C=CC2=C(C(=N1)C(=O)NCC(=O)O)O)OC3=CC=CC=C3

Properties

• Density: 1.4$+/-$0.1 g/cm³ Calc.^*
• Boiling point: 684.3$+/-$55.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 367.6$+/-$31.5 $degree$C (Calc.)^*
• Solubility: DMSO 86 mg/m, Water $lessThan$1 mg/mL, Ethanol 7mg/mL (Expl.)
• Index of refraction: 1.674 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

N-[(4-Hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine is a synthetic organic compound featuring an isoquinoline-derived aromatic heterocyclic core linked through an amide bond to glycine. Its structure combines a substituted isoquinoline scaffold with a simple amino acid moiety, forming a conjugated heteroaromatic carboxamide system. The compound belongs to the broader class of isoquinoline carboxamide derivatives, which are frequently encountered in medicinal and heterocyclic chemistry.

The core structural unit is a 3-isoquinolinyl framework, a bicyclic aromatic heterocycle composed of a fused benzene and pyridine-like ring. This isoquinoline ring is substituted at multiple positions: a hydroxyl group at position 4, a methyl group at position 1, and a phenoxy group at position 7. These substituents significantly modify the electronic distribution of the aromatic system. The hydroxyl group can participate in hydrogen bonding, while the phenoxy substituent extends aromatic conjugation and increases lipophilicity.

At the 3-position of the isoquinoline ring, a carbonyl linker forms an amide bond to glycine, producing a carboxamide structure. Glycine is the simplest amino acid, containing a single hydrogen as its side chain. In this compound, glycine contributes a terminal carboxyl group and an amide linkage, increasing polarity and hydrogen-bonding capacity. The amide bond connects the aromatic heterocycle to the amino acid fragment, forming a stable but chemically functional linkage.

The overall molecule contains multiple functional groups, including phenolic hydroxyl, aromatic ether (phenoxy), tertiary aromatic heterocycle, amide, and carboxylic acid functionalities. This combination creates a balance of hydrophilic and hydrophobic regions, which is a common feature in bioactive small molecules designed for interaction with biological targets.

From a structural perspective, the isoquinoline ring system is relatively rigid and planar, promoting π–π stacking interactions. The phenoxy group at the 7-position introduces additional rotational freedom and increases the spatial complexity of the molecule. The methyl group at position 1 further influences steric and electronic properties of the heterocycle.

The synthesis of such compounds typically involves stepwise functionalization of an isoquinoline precursor. Introduction of hydroxyl, methyl, and phenoxy substituents is achieved through electrophilic aromatic substitution, nucleophilic aromatic substitution, or etherification reactions, depending on the reactivity of the intermediate. The final step generally involves activation of the isoquinoline carboxylic acid derivative and coupling with glycine under amide bond-forming conditions, such as carbodiimide-mediated coupling.

Compounds of this general type are often investigated in medicinal chemistry due to the presence of the isoquinoline scaffold, which is a common pharmacophore in biologically active molecules. The combination of heteroaromatic rigidity and hydrogen-bonding functionality allows interaction with enzyme active sites or receptor binding pockets. However, specific biological activity depends on detailed structural context and substitution pattern.

The glycine moiety contributes to increased polarity and potential aqueous solubility relative to purely aromatic isoquinoline derivatives. It also introduces ionizable functional groups (carboxyl and amine-derived amide linkage), which can influence the compound’s behavior in different pH environments.

Overall, N-[(4-hydroxy-1-methyl-7-phenoxy-3-isoquinolinyl)carbonyl]glycine is a multifunctional isoquinoline-based amide incorporating aromatic, ether, phenolic, and amino acid-derived structural elements. Its design reflects typical strategies in heterocyclic and medicinal chemistry, where rigid aromatic scaffolds are combined with polar functional groups to tune chemical properties and potential biological interactions.

References

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