Deuterocactinib (CAS: 1609392-27-9) | TYK2 Inhibitor API, Indications, Efficacy, and Supply Solutions for Three Key Deuterated Intermediates

Deuterocactinib (CAS: 1609392-27-9) | TYK2 Inhibitor API, Indications, Efficacy, and Supply Solutions for Three Key Deuterated Intermediates

This article details the clinical applications and pharmacological efficacy of deuterocactinib, along with three core synthetic intermediates: deuterated methylamine hydrochloride 7436-22-8, 4,6-dichloro-N-(methyl-d3)-3-pyridazine carboxamide 1609393-89-6, and sodium 4,6-dihydroxypyridazine-3-carboxylate 1442437-21-9. We provide high-purity API and intermediate customization, kilogram-scale mass production, and process optimization services, supplying globally to pharmaceutical CROs/CDMOs.

1.1 Product Basic Core Parameter Table

Table Item Parameter Details

Generic Name Deucravacitinib

CAS No. 1609392-27-9

Trade Name Sotyktu

Target TYK2 (Tyrosine Kinase 2) Allosteric Inhibitor

Drug Type Oral Small Molecule Innovative API, Deuterated Patented Drug

Approved Indication Moderate to Severe Plaque Psoriasis (PsO) in Adults Systemic / Phototherapy Alternative

Dosage Once Daily Oral

Core Process Intermediate 1. Deuterated Methylamine Hydrochloride METHYL-D3-AMINE HYDROCHLORIDE CAS:7436-22-82. 4,6-Dichloro-N-(Methyl-d3)-3-pyridazine carboxamide CAS:1609393-89-63. 4,6-Dihydroxypyridazine-3-carboxylate Sodium CAS: 1442437-21-9

Supply Specifications: Laboratory gram-level, pilot-scale hundred-gram-level, commercial kilogram/ton-level (customized)

Purity Standards: API ≥ 99.5%; Intermediates ≥ 98.0%, Isotope Abundance D3 ≥ 99 atom%

1.2 Industry Background

Deuterocolicitinib is the world’s first and only approved oral allosteric inhibitor of TYK2. It was approved by the Chinese NMPA in 2023 and by the US FDA in 2022. There are over 64 million psoriasis patients globally, and over 3.8 million moderate to severe patients in China. Traditional JAK inhibitors, which inhibit all kinases, pose cardiovascular and infectious safety risks. Deucravacitinib, relying on its unique deuterated methyl structure, achieves high selectivity for TYK2, avoiding off-target side effects. It is a milestone drug for oral targeted therapy of psoriasis. The continuous expansion demand from global pharmaceutical companies and CROs/CDMOs has made the upstream deuterated intermediate supply chain a bottleneck in production capacity.

2. Deuterocelexitinib Core Applications and Pharmacological Efficacy

2.1 Core Clinical Applications

1. First-line Indication: Moderate to severe plaque psoriasis in adults. For patients who cannot tolerate injectable biologics, have poor response to phototherapy, or have limited efficacy with traditional oral medications, it is administered orally as a monotherapy daily, without the need for combination therapy with hormones.

2. Expanding Clinical Research Directions: Phase III clinical trials cover autoimmune inflammatory diseases such as psoriatic arthritis, systemic lupus erythematosus, and ulcerative colitis, indicating a broad market growth potential.

2.2 Mechanism of Action and Core Efficacy

1. Precise TYK2 Allosteric Inhibition Mechanism: Selectively binds to the TYK2 regulatory domain, blocking the IL-12, IL-23, and type I interferon inflammatory pathways, without inhibiting JAK1/2/3, significantly reducing the risk of thrombosis, infection, and dyslipidemia.

2. Skin Lesion Clearance Efficacy: After 16 weeks of treatment, over 69% of patients achieved near-complete lesion clearance (sPGA 0/1), with rapid reduction of itching, scaling, and erythema; long-term maintenance efficacy lasted for 52 weeks with no significant efficacy attenuation.

3. Unique Advantages of the Deuterated Structure: The methyl-d3 isotope substitution in the molecule prolongs the drug’s in vivo half-life, reduces dosing frequency, increases in vivo exposure, and reduces metabolic byproducts. This is the core structure of the patented drug and must be synthesized using a deuterated intermediate.

3. Detailed Explanation of the Three Key Intermediates in the Synthesis of Deucravacitinib The entire industrial synthetic route uses sodium 4,6-dihydroxypyridazine-3-carboxylate (1442437-21-9) as the parent material. Chlorination and amide condensation introduce deuterated methylamine hydrochloride (7436-22-8) to obtain the key advanced intermediate 4,6-dichloro-N-(methyl-d3)-3-pyridazine carboxamide (1609393-89-6). Further multi-step cyclization and substitution yields the final product, deuterocolicinib API.

3.1 Intermediate 1: Sodium 4,6-dihydroxypyridazine-3-carboxylate CAS:1442437-21-9

· Function: Starting building block for the pyridazine core, constructing the core six-membered heterocyclic skeleton of the drug;

· Process value: The purity of the core directly determines the level of related substances in the final product, making it the core raw material for the first step in the entire synthetic route;

· Supply standard: Sodium salt monohydrate, HPLC ≥98.5%, heavy metals <10ppm, meeting the pharmacopoeia starting material standards.

3.2 Intermediate 2: METHYL-D3-AMINE HYDROCHLORIDE (Deuterated Methylamine Hydrochloride) CAS: 7436-22-8

· Function: Provides the essential methyl-d3 deuterated isotope group for drug patents, and is the sole source of the differentiated structure of deuterated colexitinib;

· Process Value: Isotope abundance D3 ≥ 99 atom% is a strict quality control indicator. Insufficient abundance will produce non-deuterated impurities, affecting drug application;

· Application Limitations: Domestic mass-production manufacturers are scarce, and conventional methylamine cannot replace it, making it a core bottleneck raw material in the supply chain.

3.3 Intermediate 3: 4,6-Dichloro-N-(methyl-d3)-3-pyridazine carboxamide CAS: 1609393-89-6

·Function: Advanced key intermediate, precursor with intact core + deuterated methyl structure, only 3-5 reaction steps away from API;

·Process value: Can be directly supplied to CDMO, shortening the synthesis cycle by 30%, eliminating the high-risk deuteration condensation step for customers;

·Quality control advantages: We provide pre-purified finished product, with single impurities <0.1%, eliminating the need for secondary recrystallization by customers.

Summary Table of Three Intermediate Parameters

Table Intermediate Name CAS Number Core Use Key Quality Control Indicators Synthesis Stage

4,6-Dihydroxypyridazine-3-carboxylate Sodium 1442437-21-9 Pyridazine core starting material HPLC≥98.5% First step in synthesis

Deuterated methylamine hydrochloride METHYL-D3-AMINE HYDROCHLORIDE 7436-22-8 Introduction of deuterated d3 methyl patent group D3 isotopic abundance≥99atom% Amide condensation step

4,6-Dichloro-N-(methyl-d3)-3-pyridazine carboxamide 1609393-89-6 High-grade API precursor Single impurity ≤0.1% Key intermediate in the middle stage of synthesis

4. FAQ Q&A Section

Q1: Deuterocolicitinib Deucravacitinib CAS1609392-27-9 Q1. What diseases does it primarily treat?

A: Approved for moderate to severe plaque psoriasis in adults; clinically investigated for psoriatic arthritis, lupus erythematosus, and other autoimmune inflammatory diseases. It is the world’s only oral TYK2 allosteric inhibitor.

Q2. What are the core intermediates required for the synthesis of deuterated lexicitinib?

A: Three irreplaceable intermediates: 1. Sodium 4,6-dihydroxypyridazine-3-carboxylate 1442437-21-9; 2. Deuterated methylamine hydrochloride 7436-22-8; 3. 4,6-dichloro-N-(methyl-d3)-3-pyridazine carboxamide 1609393-89-6. The patented deuterated structure cannot be synthesized without any one of these.

Q3. Can deuterated methylamine hydrochloride 7436-22-8 be replaced with ordinary methylamine?

A: No, it cannot be replaced. Deucravacitinib achieves its metabolic advantage and patent protection through the use of the methyl-d3 isotope. Ordinary methylamine lacks deuterium labeling, and its products contain excessive impurities, making drug registration impossible.

Q4: What specifications of deuterated lecithinib API and intermediates can your company supply?

A: Gram-level laboratory samples, 100g-5kg pilot-scale batches, and over 10kg commercial production batches; we can provide customized purification, impurity standards, and a complete set of application documents including COA/analytical methods.

Q5: What are the safety advantages of deuterated lecithinib compared to traditional JAK inhibitors?

A: It targets only the TYK2 regulatory domain, without inhibiting JAK1/2/3, significantly reducing adverse reactions such as cardiovascular risk, serious infections, and elevated blood lipids. Long-term oral administration is also better tolerated.

5. Company Supply Advantages

1. Full-Chain Support: Simultaneously supplying parent nucleus raw materials, deuterated building blocks, advanced intermediates, and finished product Deucravacitinib API, providing one-stop procurement and reducing supply chain costs;

2. Stable Isotope Production Capacity: Own deuteration synthesis workshop, ensuring stable mass production of deuterated methylamine hydrochloride with consistently compliant D3 abundance;

3. Application-Grade Documentation: Providing COA, NMR, mass spectrometry, and HPLC chromatograms for each batch, supporting ANDA and IND applications for overseas pharmaceuticals;

4. Global Logistics: Supporting FOB Shanghai/Guangzhou, compliant dangerous goods exports to Europe, America, and Southeast Asia, with temperature-controlled packaging throughout;

5. Process Optimization Services: Assisting clients in optimizing the yield of condensation and chlorination steps, reducing waste and production costs.

6. Conclusion

If you are engaged in the research and development of innovative drugs for psoriasis, CDMO commercial production, or API procurement, and need high-purity Deucravacitinib API (1609392-27-9) or samples/mass production quotations for the three core intermediates, please feel free to leave a message online, email, or call to obtain COA samples and process technology white papers.