H1 Title: Esaxerenone CAS 1632006-28-0 | Indications, Pharmacological Efficacy, and Complete Set of Key Pharmaceutical Intermediates
I. What is Esaxerenone?
Quick Answer: Esaxerenone (development code CS-3150) is a third-generation, highly selective nonsteroidal mineralocorticoid receptor antagonist (MRA), CAS 1632006-28-0, developed by Daiichi Sankyo. It was approved for marketing in Japan in 2019 and is primarily used for the clinical treatment of essential hypertension, type 2 diabetic nephropathy, and hyperaldosteronism. It is currently a preferred first-line drug API for kidney disease complicated with hypertension. Detailed Explanation: Unlike traditional spironolactone and eplerenone, esalidomide exhibits a selectivity for aldosterone MR receptors that is over a thousand times higher, with receptor affinity 4 times that of spironolactone and 76 times that of eplerenone. It has no steroid hormone cross-interactions, high oral bioavailability, long-lasting and stable blood pressure control, and a low risk of hyperkalemia, making it suitable for long-term use in diabetic patients with kidney damage. Molecular formula: C₂₂H₂₁F₃N₂O₄S, molecular weight 466.47; appearance: off-white crystalline powder, pharmaceutical grade purity ≥99.0%, widely used in formulation development, clinical generic drugs, and pharmacological research experiments.
II. Core Clinical Applications and Pharmacological Efficacy of Isaridone
H3 1. Main Clinical Indications
1. Primary hypertension in adults: Stable blood pressure reduction as monotherapy/in combination with calcium channel blockers, 2.5 mg daily as the usual dose, maximum 5 mg/day;
2. Type 2 diabetes mellitus complicated with hypertension and diabetic nephropathy (DKD): Reduces urinary albumin excretion and delays glomerular fibrosis;
3. Adjunctive treatment for primary aldosteronism, inhibiting aldosterone-mediated sodium and water retention and vascular remodeling.
H3 2. Clear Pharmacological Efficacy
1. Powerful and Long-Lasting Antihypertensive Effect: 6-month clinical data showed that patients with a baseline systolic blood pressure of 155.2 mmHg experienced a reduction to 132.9 mmHg after medication, with a simultaneous and significant decrease in diastolic blood pressure, and stable diurnal blood pressure without fluctuations (PMC).
2. Core Renal Protective Effect: 3-year follow-up data showed an average decrease of 63.8% in the urine albumin/creatinine ratio (UACR), reducing glomerular hyperfiltration and delaying renal function decline, superior to traditional MRA drugs (PMC).
3. Comprehensive Metabolic Benefits: Simultaneously reduces glycated hemoglobin, transaminases, and low-density lipoprotein, suitable for obese individuals, those with fatty liver, and hypertension.
4. Safety Advantages: Non-steroidal structure, extremely low masculinizing and sex hormone interference side effects, and a significantly lower incidence of hyperkalemia compared to spironolactone. III. Synthetic Route of Isalidone and 4 Key Intermediates
The core skeleton of the total synthesis of isalidomide is an axially chiral pyrroleic acid structure. The complete synthetic chain is: construction of pyrrole ethyl ester core → N-hydroxyethylation → chiral resolution → amide condensation to obtain the finished API. This time, the company has achieved stable mass production of 4 key intermediates covering the entire process from starting materials to the core chiral resolution stage. The parameters are standardized to meet the needs of pharmaceutical CDMOs and generic drug R&D procurement.
H3 Detailed Explanation of the Step-by-Step Synthesis and Applications of Each Intermediate
1. 1631030-76-6 Pyrroleic Acid Ethyl Pyrrole: Prepared through a modified Knorr pyrrole cyclization process, the pyrrole core is obtained by coupling with 2-trifluoromethylphenylboronic acid, which is the most upstream stable building block of the entire process. After hydrolysis, racemic carboxylic acid 1631030-72-2 is obtained without column chromatography, with an industrial-scale production yield of over 82%, significantly reducing production costs for pharmaceutical companies.
2.1631030-72-2 Racemic pyrrole carboxylic acid: Prepared from ethyl pyrrole via N-hydroxyethylation of ethylene carbonate and alkaline hydrolysis in two steps, with an overall yield of 94%. The molecule contains an axially chiral racemic mixture, requiring salt resolution to obtain a single active S-configuration intermediate, serving as a bridge between the parent nucleus and the chiral segment.
3.1632002-11-9 S-configuration chiral pyrrole carboxylic acid (core value intermediate): Isalidone’s efficacy depends entirely on the 5-position S-axis chirality. This intermediate is resolved by low-temperature recrystallization of the racemic mixture, with a de value ≥98%. It undergoes amide condensation with a 4-methanesulfonyl group to produce the finished product, isalidomide (CAS 1632006-28-0), in one step. This is a crucial core material for generic drug manufacturers and process optimization companies. Our company can provide resolution process technology support services.
IV. Our Advantages in Ithalidomide API and Intermediate Supply
1. Integrated Full-Chain Capacity: We independently synthesize all intermediates from the parent ethyl ester to the chiral carboxylic acid, simultaneously supplying ixalidomide API, avoiding losses from multiple supplier purchases;
2. Pharmaceutical-Grade Quality Control Standards: Intermediate HPLC purity, chiral ee/de value, moisture, heavy metals, and residual solvents fully comply with ICH Pharmacopoeia standards, providing COA and process validation documents;
3. Customized CDMO Services: Supporting kilogram-level to ton-level mass production, we can assist clients in optimizing splitting and condensation processes to reduce waste and production costs;
4. Stable Export Delivery: Packaging specifications include 1kg/aluminum foil bag and 25kg cardboard drum, with accompanying export customs declaration documents, serving domestic and international generic drug companies and CRO R&D institutions.
V. Frequently Asked Questions (FAQ) Module
Q1: What are the clinical advantages of ixalidomide (CAS 1632006-28-0) compared to eplerenone? Quick Answer: It leads in receptor selectivity, kidney protection, and long-term efficacy, with fewer side effects from high potassium levels. Details: Its selectivity for MR receptors is 76 times higher than eplerenone, resulting in a greater reduction in proteinuria after 3 years of long-term use; single daily dosing provides stable blood pressure control, without the endocrine disorders caused by steroid hormones, making it suitable for long-term maintenance treatment of diabetic nephropathy.
Q2: Is it necessary to purchase the chiral intermediate 1632002-11-9 for the synthesis of esalidon?
Quick Answer: For industrial mass production, it is recommended to directly purchase the S-configuration intermediate after resolution, significantly shortening the process and increasing the overall yield. Details: Self-resolution of the racemic 1631030-72-2 requires low-temperature crystallization and salt recovery equipment; small-scale laboratory testing is feasible, but the cost for large-scale production is too high. Our company has 1632002-11-9 with a de≥98%, which can be directly condensed to obtain qualified API, eliminating the resolution process.
Q3: Is 1082041-85-7 5-bromo-4-fluoro-1H-indazole directly related to the synthesis of esalidomide?
Quick Answer: It is not an intermediate in the main esalidomide synthesis process, but a heterocyclic building block for innovative drugs targeting the same target. Details: The main synthesis does not require an indazole structure; it is often used by pharmaceutical companies in the simultaneous development of next-generation mineralocorticoid receptor antagonists, serving as a one-stop procurement of parallel research materials.
Q4: What is the minimum order quantity and delivery time for esalidomide intermediates?
Quick Answer: The minimum order quantity for intermediates is 100g research-grade packaging. Kilogram-level in-stock items are delivered in 3-7 days, while ton-level production takes 15-25 days. Details: 1631030-76-6 and 1631030-72-2 are kept in kilogram-level inventory; the core chiral intermediate 1632002-11-9 is produced on demand, and process technology support documents can be provided simultaneously.
Q5: Does the esalidomide API support the submission of generic drug application materials?
Quick Answer: Yes, we can provide a complete set of original data on process, impurity studies, and stability studies. Details: API purity ≥99.0%, complete ICH impurity profiles, method validation reports, adaptable to the generic drug application requirements in China, Japan, Europe, and the US. Corresponding traceability documents for intermediates are also provided.
This article was written by our pharmaceutical API & intermediate R&D and promotion specialist, who has 8 years of experience in supply chain services for the synthesis of cardiovascular and renal MRA drugs, serving over 200 pharmaceutical companies and CRO R&D laboratories worldwide. We can provide complete esalidomide synthesis process consultation and customized mass production solutions for intermediates.
Post time: Jul-14-2026
