Abstract
Vericiguat is the world’s first long-acting oral soluble guanylate cyclase (sGC) stimulator, specially indicated for the treatment of chronic heart failure with reduced ejection fraction. It can significantly reduce the risks of cardiovascular death and heart failure hospitalization. Its industrial synthesis relies on two key heterocyclic intermediates: Ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate (CAS 256504-39-9) and Ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate (CAS 1361232-72-5). This article systematically sorts out the pharmacological efficacy, clinical value, physicochemical parameters of intermediates, synthetic routes and mass supply advantages of vericiguat, catering to the R&D and procurement demands of pharmaceutical CROs, CDMOs and API manufacturers.
1. Vericiguat CAS 1350653-20-1: Drug Efficacy and Clinical Applications
1.1 Core Basic Specification Table of Vericiguat
表格
| Item | Detailed Index |
|---|---|
| Generic Name | Vericiguat |
| CAS No. | 1350653-20-1 |
| Research Code | BAY1021189 |
| Brand Name | Verquvo |
| Molecular Formula | C₁₉H₁₆F₂N₈O₂ |
| Molecular Weight | 426.38 g/mol |
| Drug Category | Soluble Guanylate Cyclase (sGC) Stimulator |
| Appearance | White to pale yellow powder |
| Purity Standard | ≥99.5% for API, ≥98% for lab research grade |
| Storage Condition | Sealed, light-proof and dry storage at 2–8℃ |
1.2 Core Mechanism of Action & Pharmacological Efficacy
Heart failure patients generally suffer from endothelial injury and insufficient nitric oxide (NO) secretion, which inactivates the sGC pathway and reduces cGMP synthesis, further triggering vasoconstriction, myocardial remodeling and elevated cardiac load.
Vericiguat features a dual activation mechanism:
- It directly stimulates sGC enzyme activity independent of endogenous NO to stably raise intracellular cGMP concentration;
- It synergistically amplifies residual NO signals to dilate systemic arteries and veins, reduce cardiac preload and afterload, and inhibit myocardial fibrosis and ventricular hypertrophy.
Summary of core therapeutic effects:
- Dilate blood vessels, lower peripheral resistance and improve myocardial blood perfusion;
- Reverse pathological myocardial remodeling and slow down heart failure progression;
- Reduce the level of heart failure biomarker NT-proBNP and enhance exercise tolerance;
- Long-term administration lowers risks of heart failure deterioration, emergency hospitalization and cardiovascular death.
1.3 Approved Clinical Indications & Authoritative Clinical Evidence
Approved Indication: For adult patients with symptomatic chronic heart failure with reduced ejection fraction (HFrEF, EF＜45%) who have been hospitalized for decompensated heart failure or stabilized after intravenous diuretic therapy. Used in combination with standard heart failure therapies to reduce the risks of cardiovascular death and recurrent heart failure hospitalization.
Key Phase III VICTORIA Trial Data (Authoritative Evidence Reference)
A total of 5,050 high-risk heart failure patients were enrolled and treated with 10 mg vericiguat per day, with a follow-up period of 10.8 months:
- The risk of composite endpoint (cardiovascular death + heart failure hospitalization) decreased by 10%;
- The incidence of first heart failure hospitalization was markedly reduced;
- The average NT-proBNP level dropped by 34%, with more prominent benefits observed in patients with severe heart failure.
Expanding R&D Directions: Ongoing clinical trials including VICTOR and VALOR are exploring its application in heart failure with preserved ejection fraction and pediatric cardiomyopathy.
2. Full Analysis of Two Core Synthetic Intermediates for Vericiguat (CAS 256504-39-9 / CAS 1361232-72-5)
2.1 Intermediate 1: Ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate CAS 256504-39-9
Basic Specification Table
表格
| Item | Specification |
|---|---|
| Full Chemical Name | Ethyl 5-amino-1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate |
| CAS Number | 256504-39-9 |
| Molecular Formula | C₁₃H₁₄FN₃O₂ |
| Molecular Weight | 264.27 |
| Purity | ≥99.0% for industrial synthesis grade, ≥99.8% for custom high-purity grade |
| Synthetic Positioning | Key starting building block for the full synthesis of vericiguat |
Application Value
This compound serves as the upstream raw material for constructing the pyrazole core scaffold of vericiguat. It undergoes cyclization, fluorination and pyridine ring closure reactions to generate the downstream intermediate CAS 1361232-72-5, acting as the starting material of the entire synthetic route.
With a pre-installed 2-fluorobenzyl side chain, extra benzylation steps are eliminated, greatly shortening reaction steps and lowering impurity generation. It is suitable for large-scale industrial production and has become the preferred starting intermediate for mainstream manufacturing processes adopted by CDMOs worldwide.
2.2 Intermediate 2: Ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate CAS 1361232-72-5
Basic Specification Table
表格
| Item | Specification |
|---|---|
| Full Chemical Name | Ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboxylate |
| CAS Number | 1361232-72-5 |
| Molecular Formula | C₁₆H₁₃F₂N₃O₂ |
| Molecular Weight | 317.29 |
| Purity | ≥99.2% meeting pharmaceutical intermediate standards, single individual impurity＜0.1% |
| Synthetic Positioning | Core advanced intermediate for vericiguat API synthesis |
Application Value
The fused pyrazolopyridine bicyclic heterocyclic scaffold perfectly matches the parent core of vericiguat API. Only three subsequent reactions including ester hydrolysis, cyanation and pyrimidine ring condensation are required to obtain finished API products.
The difluoro-substituted structure accurately replicates the active binding site of the drug molecule with outstanding impurity controllability. Complex chromatographic purification is unnecessary, which significantly cuts API production costs. It is an irreplaceable key intermediate for current commercial mass production processes.
2.3 Upstream & Downstream Synthetic Logic of the Two Intermediates
Starting material CAS 256504-39-9 (aminopyrazole ester) → Fluorination and ring-closing reaction → Advanced intermediate CAS 1361232-72-5 (fluorinated pyrazolopyridine ester) → Cyanation, pyrimidine condensation, methyl carbamation → Finished vericiguat API CAS 1350653-20-1
3. Procurement Reference: Advantages of Our Vericiguat Intermediate Supply
- Full-chain mass production: Independent synthesis of both intermediates, impurity control complying with ICH guidelines for pharmaceutical impurities;
- Flexible packaging specifications: Spot goods ranging from 10 g to 1000 kg; customized sterile and low heavy metal ultra-high purity grades available;
- Complete compliance documents: COA, ¹H/¹³C NMR, mass spectrum and process validation reports provided to support overseas pharmaceutical enterprises’ DMF filing;
- Stable supply chain: Exclusive production line for fluorinated heterocyclic compounds with sufficient annual capacity and controllable delivery cycle, supporting long-term stocking of overseas CROs.
4. FAQ Section
Q1: What unique advantages does vericiguat have over traditional heart failure medicines?
A: Conventional RAAS inhibitors and beta-blockers work by inhibiting neuroendocrine pathways, while vericiguat directly repairs damaged NO-sGC-cGMP pathways and maintains efficacy even under NO-deficient and oxidative stress conditions in heart failure patients. It has no obvious drug-drug interactions, can be combined with standard heart failure therapies to further reduce hospitalization and mortality risks, and benefits patients with severe refractory heart failure.
Q2: Can CAS 256504-39-9 and 1361232-72-5 be purchased separately for laboratory research?
A: Both intermediates are available for individual sales. CAS 256504-39-9 can be applied in the R&D of other fluoropyrazole sGC agonists; CAS 1361232-72-5 is used for structural modification research based on vericiguat core scaffold. We provide milligram-scale lab samples to support laboratory compound screening.
Q3: What adverse impacts will substandard intermediates bring to finished vericiguat API?
A: Residual fluoride and amine impurities carried over from unqualified intermediates will introduce genotoxic risks, making the API fail FDA/EMA registration review. Our intermediates strictly control single individual impurity below 0.1%, and the final API can be directly used for formulation development.
Q4: Do you support export customs clearance and cold-chain transportation for overseas orders of intermediates?
A: We provide global export services with complete MSDS, hazard identification certificates and customs declaration documents. Temperature-sensitive intermediates are packed in vacuum cold packaging with full real-time temperature tracking, and we have long-term stable cooperation with pharmaceutical manufacturers across Europe, America and Southeast Asia.
5. Conclusion & CTA Conversion Guidance
As a blockbuster innovative API for heart failure treatment, vericiguat is witnessing surging global demand for pharmaceutical formulations. Its two upstream core intermediates CAS 256504-39-9 and CAS 1361232-72-5 are essential raw materials for industrial API manufacturing.
We have years of professional experience in fluorinated heterocyclic pharmaceutical intermediates, stably supplying high-purity upstream and downstream building blocks of vericiguat for full scenarios including CRO new drug discovery, CDMO commercial production and university pharmacology research.
If you need COA samples, quotations or complete synthetic technical documents, please contact our sales team for one-on-one technical support.
Post time: Jul-09-2026
