FDA GRANTS ACCELERATED APPROVAL PIRTOBRUTINIB

Active name:	Pirtobrutinib
Brand name:	Jaypirca
Innovator name	LOXO ONCOLOGY ING
Approval Date:	Jan 27, 2023
Therapeutic activity:	kinase inhibitor used to treat relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy.
Route of adminstration	Tablet, oral
Structure
Chemical name	5-amino-3-{4-[(5-fluoro-2-methoxybenzamido)methyl]phenyl}-1-[(2S)- 1,1,1-trifluoropropan-2-yl]-1H-pyrazole-4-carboxamide
CAS	2101700-15-4
Dosage:	50 &100 mg
MDD	200 mg
Molecular weight& molecular formuale	479.44 & C₂₂H₂₁F₄N₅O₃
OB patents	US 10342780 B2; US10464905 B2; US10695323 B2 (12/16/2036)
Polymorhic patent	US 2021330643A1; WO2022240920A1; WO2020028258A1
NCE	01/27/2028; ODE-424 01/27/2028; ODE-451 12/01/2030
Solubility data	Insoluble in water range pH 1 to 7
Hygroscopicity	Not hygroscopic
Pubchem CID	129269915
Drugbank	DB17472
Chemspider	114875989

Patent Data

Patent No	Patent Expiration	Drug Substance	Drug Product	Submission Date
10342780	12/16/2036	DS	DP	02/10/2023
10464905	12/16/2036			02/10/2023
10695323	12/16/2036	DS	DP	02/10/2023
10918622	12/16/2036			02/10/2023
12109193	09/14/2041		DP	10/31/2024

Synthesis:

Scheme-1: Ref: US 10342780B2

The synthesis of Pirtobrutinib started with 5-Fluoro-2-methoxy benzoic acid, react with thionyl chloride followed by amidation with 4-(aminomethyl)benzoicacid to form intermediate3. Intermediate 3 treated with thionyl chloride followed by malononitrile to afford Intermediate II. Intermediate-II couple with compound 8 to give the Pirtobrutinib. This was disclosed in WO2022/056100.