Zofenoprilat is a synthetic small-molecule active pharmaceutical ingredient and the active sulfhydryl metabolite of the angiotensin-converting enzyme (ACE) inhibitor prodrug zofenopril. It belongs to the ACE inhibitor class and contains a free sulfhydryl group that contributes to its interaction with angiotensin-converting enzyme.
Zofenoprilat is identified by CAS Number 75176-37-3, molecular formula C15H19NO3S2, and molecular weight approximately 325.5 g/mol. PubChem identifies Zofenoprilat as a proline derivative, thiol, aryl sulfide and N-acyl-L-amino acid.
The compound is also known as zofenoprilate, zofenoprilatum, and SQ-26333. Its systematic chemical name is (2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid.
Zofenoprilat is structurally related to zofenopril but differs in the substituent attached to the thiol-containing side chain. Zofenopril contains a benzoyl-protected sulfhydryl group and functions as a prodrug, whereas metabolism of zofenopril produces the active compound Zofenoprilat.
Zofenoprilat contains three defined stereocenters and has the molecular formula C15H19NO3S2. PubChem reports an exact mass of 325.08063582 Da and a calculated molecular weight of 325.5 g/mol.
The presence of a free thiol group is an important structural characteristic of Zofenoprilat and distinguishes it from the thioester-containing prodrug Zofenopril.
Zofenoprilat acts as an angiotensin-converting enzyme inhibitor. It inhibits ACE, the enzyme responsible for conversion of angiotensin I to angiotensin II.
Reduction of angiotensin II formation decreases vasoconstrictor activity and reduces stimulation of aldosterone secretion. This contributes to vasodilation and changes in sodium and water handling.
Zofenopril itself is administered as a prodrug and is hydrolyzed in vivo to Zofenoprilat, which represents the pharmacologically active sulfhydryl-containing form. PubChem and IUPHAR/BPS identify Zofenoprilat as the active form of Zofenopril.
Zofenoprilat is primarily associated with cardiovascular pharmaceutical research and ACE-inhibitor pharmacology. Zofenopril, its prodrug, is used as an antihypertensive and cardioprotective agent, while Zofenoprilat represents its active pharmacological form.
The compound is relevant to pharmaceutical research involving:
IUPHAR/BPS identifies Zofenoprilat as an approved drug-related active metabolite and describes its use in relation to hypertension and coronary heart disease.
It is important not to combine Zofenoprilat specifications with Zofenopril specifications.
Zofenopril:
Zofenoprilat:
These are chemically different substances. PubChem specifically describes Zofenopril as a prodrug for Zofenoprilat.
Zofenoprilat is a stereochemically defined organic molecule containing a carboxylic acid, amide, thiol and aryl-sulfide functionality.
PubChem reports:
Zofenoprilat is a small-molecule API and can be characterized using chromatographic and spectroscopic techniques.
HPLC or UPLC can be used for assay and related-substance analysis. LC-MS can provide molecular confirmation, while FTIR and other spectroscopic techniques can support identity testing.
Because Zofenoprilat contains a free sulfhydryl group, control of oxidation-related degradation products is particularly relevant during pharmaceutical development and storage.
Analytical methods should therefore be capable of distinguishing Zofenoprilat from related substances, degradation products and the parent prodrug Zofenopril.
Important quality attributes for Zofenoprilat may include:
The exact numerical acceptance criteria should be established using the applicable validated analytical method and approved specification. Public chemical databases confirm identity and physicochemical characteristics but do not establish a universal commercial API release specification for every quality parameter.
Zofenoprilat contains both ionizable carboxylic-acid and sulfhydryl functionalities, so its apparent solubility can depend substantially on pH and the experimental medium.
I would not recommend inserting an unsupported single numerical water-solubility value into the SDP CMS. If a batch-specific or validated solubility value is available from your supplier's CoA/specification, it can be added with the corresponding test conditions.
Zofenoprilat is relevant to pharmaceutical research and API development involving ACE inhibitors and cardiovascular medicines.
A pharmaceutical-grade Zofenoprilat supply program should provide appropriate analytical documentation covering identity, assay, related substances, residual solvents, water content and elemental impurities.
Because Zofenoprilat is the active sulfhydryl metabolite of Zofenopril, correct identification of the API is particularly important when preparing technical documentation, specifications and regulatory records.
Zofenoprilat should be stored under validated conditions appropriate for the API and packaging configuration. Particular attention should be given to protection from excessive moisture, heat and oxidative conditions because of the presence of the free sulfhydryl group.
The final storage conditions should be based on stability data generated for the specific API form and packaging system.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 98.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |