Active  name:	ENSARTINIB HYDROCHLORIDE
Brand name:	ENSACOVE
Innovator name	XCOVERY HOLDINGS INC
Approval Date:	Dec 18, 2024
Therapeutic activity:	ENSACOVE is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).
Route of administration	Capsule, oral
Structure
Chemical name	6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-{4-[(3R,5S)- 3,5-dimethylpiperazine-1-carbonyl]phenyl}pyridazine-3-carboxamide, dihydrochloride
CAS	1370651-20-9
Dosage	25 mg base eq (28.25 mg of  hydrochloride)& 100 mg base eq (113.02 mg of  hydrochloride)
MDD	225 mg
Molecular weight& molecular formuale	634.4 g/mol & C26H27Cl2FN6O3.2HCl
Solubility	Ethanol, DMSO, DMF
OB patents	US8551995B2; US9126947B2;US9296724B2; US10899744B2.
Polymorhic patent	US2019/0135792;US2023/0227413A1
NCE	12/18/2029
Solubility data	Insoluble in water.
Hygroscopicity	Not hygroscopic
Drugbank	DB14860
Chemspider	58828042
Pubchem CID	56960363

Patent Data

 

Orange book Patent Data

Patent Data

Product No	Patent No	Patent Expiration	Drug Substance	Drug Product	Patent Use Code	Delist Requested	Submission Date
001	8551995	02/09/2029	DS				01/17/2025
001	9126947	11/29/2031	DS				01/17/2025
001	9296724	06/18/2029	DS		U-4099		01/17/2025
001	10899744	06/01/2037	DS		U-4099		01/17/2025

Synthesis of ENSARTINIB:

ROS-1: Ref:WO2012/048259

Dichloropyridazine with ammoniumhydroxide furnished amino-pyridazine in 82% yield. The treatment with bromine under basic conditions 4-bromo-6-chloropyridazin-3-amine.

 N-Boc-D-proline react with alcohol EDCI-HOBt conditions to deliver ester, then separated isomer 51% yield. Later couple 4-bromo-6-chloropyridazin-3-amine  and sodium hydride in THF led the regioselectively (R)-6-chloro-4-(1-(2,6-dichloro-4-fluorophenyl)ethoxy)pyridazin-3-amine.  After sequential reactions it converted into Ensartinib dihydrochloride.

References:

1) WO2009/154769A1

2) CN103298806B

3) US2019/0135792A1