Crystal form of acid addition salt of furopyrimidine compound
Inventors
Oh, Hee Sook • Jung, Jae Hyuk • Jeon, Ji Young • JANG, Sun Young • Ha, Tae Hee
Assignees
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Publication Number
US-12227510-B2
Publication Date
2025-02-18
Expiration Date
Abstract
Provided are crystalline forms of acid addition salts of N-(3-(2-(4-(4-methylpiperazin-1-yl)phenylamino)furo[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide, and a pharmaceutical composition including the same. The crystalline forms may be easily used in preparing the pharmaceutical composition including the same as an active ingredient.
Core Innovation
The invention relates to crystalline form of an acid addition salt of a compound of Formula 1. The crystalline form is selected from dihydrochloride trihydrate (2HCl·3H2O), monohydrochloride dihydrate (1HCl·2H2O), monohydrochloride anhydrous (1HCl), methanesulfonic anhydride (1MsOH), methanesulfonate monohydrate (1MsOH·1H2O), and ethanesulfonic anhydride (1EsOH). Each crystalline form is characterized by an X-ray powder diffraction (XRPD) spectrum measured with a Cu-Kα light source.
The crystalline forms are defined by specific diffraction-angle peaks at diffraction angles (2θ) with Cu-Kα irradiation. For each contemplated salt form, a respective peak set is given, supporting identification and reproducibility of crystallinity. The document further characterizes the crystalline forms using physicochemical assessments including water content, DSC endotherms and melting/dehydration, DVS hygroscopicity, and comparison of water solubility versus amorphous or free base.
The disclosed acid addition salts are incorporated into pharmaceutical compositions comprising one or more pharmaceutically acceptable carriers or diluents. Therapeutic indications are described in connection with EGFR tyrosine kinase inhibition by the underlying compound, including cancer, inflammatory diseases, and autoimmune disease such as rheumatoid arthritis. The document emphasizes improved water solubility, stability, crystallinity reproducibility, and low hygroscopicity for the crystalline salt forms.
Claims Coverage
The patent includes two independent claims. Claim 1 covers crystalline forms, and Claim 2 covers pharmaceutical compositions containing those crystalline salt forms, with the crystalline forms defined by XRPD peak sets and Cu-Kα irradiation.
Crystalline acid addition salt forms defined by XRPD peak sets
A crystalline form of an acid addition salt of the compound of Formula 1, selected from dihydrochloride trihydrate (2HCl·3H2O), monohydrochloride dihydrate (1HCl·2H2O), monohydrochloride anhydrous (1HCl), methanesulfonic anhydride (1MsOH), methanesulfonate monohydrate (1MsOH·1H2O), or ethanesulfonic anhydride (1EsOH), wherein the crystalline form has an XRPD spectrum comprising defined diffraction-angle peaks when irradiated with a Cu-Kα light source.
Pharmaceutical compositions containing the crystalline acid addition salt forms with XRPD definition
A pharmaceutical composition comprising a crystalline form of an acid addition salt of the compound of Formula 1 and one or more pharmaceutically acceptable carriers or diluents, wherein the crystalline form is selected from the same enumerated salt identities and hydration states, and the crystalline form has an XRPD spectrum with defined diffraction-angle peaks when irradiated with a Cu-Kα light source.
Across the independent claims, the core inventive scope is limited to specific crystalline acid addition salt forms of the compound of Formula 1. Each allowable crystalline form is strictly defined by an enumerated XRPD Cu-Kα diffraction peak set, and Claim 2 further limits the invention to pharmaceutical compositions that include one or more pharmaceutically acceptable carriers or diluents.
Stated Advantages
Improved water solubility versus amorphous/free base.
Improved stability.
Crystallinity reproducibility.
Low hygroscopicity.
Documented Applications
Therapeutic indications for the pharmaceutical composition include cancer, inflammatory diseases, and autoimmune disease such as rheumatoid arthritis, linked to EGFR tyrosine kinase inhibition by the underlying compound.
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