Dirozalkib

CAS 1893419-37-8

MF C27H32ClN5O4S MW558.1 g/mol

 5-chloro-2-N-(6-methyl-5-piperidin-4-yl-2,3-dihydro-1,4-benzodioxin-8-yl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine

2,4-Pyrimidinediamine, 5-chloro-2-[2,3-dihydro-7-methyl-8-(4-piperidinyl)-1,4-benzodioxin-5-yl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-

anaplastic lymphoma kinase (ALK) inhibitor, antineoplastic, XZP-3621, XZP 3621, Xuanzhu Biopharmaceutical, 2FH56C28YT

Dirozalkib (XZP-3621) is a novel, potent, and highly selective ALK/ROS1 tyrosine kinase inhibitor developed by Xuanzhu Biopharmaceutical to treat advanced ALK-positive non-small cell lung cancer (NSCLC). It demonstrated high efficacy (47.4% ORR, up to 89.3% in naive patients) in clinical trials and is designed to overcome resistance to earlier inhibitors.

Key Aspects of Dirozalkib

• Indication: Treatment of adult patients with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
• Mechanism: Acts as a dual-target ALK/ROS1 tyrosine kinase inhibitor (TKI), effective against ALK fusion-positive cells and various resistance mutations.
• Clinical Efficacy (Phase I/II): In studies, the drug showed significant antitumor activity with an Objective Response Rate (ORR) of 47.4% and an 89.3% ORR in ALK inhibitor-naive patients at 500 mg/day.
• Safety Profile: No dose-limiting toxicities occurred; the maximum tolerated dose was 600 mg/day, with a recommended dose of 500 mg/day. Common adverse events included diarrhea.
• Status: As of early 2026, the NDA (New Drug Application) for Dexitinib (Dirozalkib) was accepted by China’s NMPA, with potential for further market expansion.

• OriginatorXuanzhu Biopharmaceutical
• Class2 ring heterocyclic compounds; Amines; Aniline compounds; Antineoplastics; Chlorinated hydrocarbons; Piperidines; Pyrimidines; Small molecules; Sulfones
• Mechanism of ActionAnaplastic lymphoma kinase inhibitors
• RegisteredNon-small cell lung cancer
• 26 Aug 2025Chemical structure information added.
• 22 Aug 2025Registered for Non-small cell lung cancer (Late-stage disease) in China (PO) – First global approval
• 22 Aug 2025Efficacy and adverse events data from a phase III trial in Non-small cell lung cancer released by Xuanzhu Biopharmaceutical

• A Phase I Study of XZP-3621 in Chinese Patients With ALK or ROS1 Rearrangement Non-small Cell Lung CancerCTID: NCT05055232Phase: Phase 1Status: CompletedDate: 2025-07-24
• Food Effect and Mass Balance Study of XZP-3621 TabletsCTID: NCT05034120Phase: Phase 1Status: CompletedDate: 2025-05-25
• A Study of XZP-3621 in Chinese Patients With ALK Positive NSCLCCTID: NCT05482087Phase: Phase 2Status: Unknown statusDate: 2022-08-01
• A Study to Evaluate and Compare the Efficacy and Safety of XZP-3621 Versus CrizotinibCTID: NCT05204628Phase: Phase 3Status: Unknown statusDate: 2022-01-24

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US412495595&_cid=P11-MOS0LI-66429-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016050171&_cid=P11-MOS088-57627-1

Example 3 Preparation of 2-((5-chloro-2-((7-methyl-8-(piperidin-4-yl)-2,3-dihydrobenzo[b][1,4]dioxin- 5-yl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide (compound 3)

(5) Preparation of 2-((5-chloro-2-((7-methyl-8-(piperidin-4-yl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide

75 mg (0.114 mmol) of tert-butyl 4-(8-((5-chloro-4-((2-(N,N-dimethylaminosulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-6-methyl-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)piperidine-1-carboxylic acid ester was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1 mL) was added. The mixture was stirred at room temperature for 12 hours. The starting material disappeared as detected by TLC. Water (20 mL) was added, and the mixture was separated. The aqueous phase was extracted twice with dichloromethane (20 mL × 2). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography (methanol:dichloromethane = 1:50) to obtain the final product (30 mg, yield 47.2%). 

[0415]_Molecular formula: 

_{C26H31ClN6O4S Molecular weight: 559.08} LC-MS (m / z): 280.2 [ M /2+H ] ⁺

[0416]

¹H-NMR(400MHz,MeOD)δ:8.44(d,1H,J＝1.2),8.11(s,1H),7.86(d,1H,J＝1.2),7.56-7.60(m,1H),7.28-7.35(m,2H),4.26(s,4H),3.45-3.48(m,2H),3.06-3.15(m,3H),2.56-2.74(m,8H),2.17(s,3H),1.76-1.80(m,2H).

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References

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• Pharmaceutical composition of anaplastic lymphoma kinase inhibitor and preparation method thereforPublication Number: WO-2025140560-A1Priority Date: 2023-12-28
• CRYSTALLINE FORM OF A POLYCYCLIC ANAPLASIC LYMPHOMA KINASE INHIBITORPublication Number: EP-4092021-A4Priority Date: 2020-01-17
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• Crystal form of polycyclic anaplastic lymphoma kinase inhibitorPublication Number: EP-4092021-A1Priority Date: 2020-01-17

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