Method of inhibiting kinase by mesylate salts of triazolopyrazine derivatives
Inventors
Choi, Jun Young • PARK, Kyung-eui • Kim, Na Young
Assignees
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Publication Number
US-12528817-B2
Publication Date
2026-01-20
Expiration Date
Abstract
Disclosed are a salt (mesylate salt) of methanesulfonic acid and a triazolopyrazine derivative of formula (1), pharmaceutical compositions thereof, methods of making the salt, and therapeutic use thereof:
Core Innovation
The described invention relates to novel mesylate-salt forms of a triazolopyrazine c-Met kinase inhibitor identified as ABN-401, and to pharmaceutical compositions containing these mesylate salts. The document states that mesylate-salt forms are provided in view of prior free-base forms of the triazolopyrazine derivative of formula (1), and it describes rationale for using the mesylate salt form.
The document links the therapeutic use to inhibiting c-Met kinase in subjects, and it describes administration of a therapeutically effective amount of the mesylate salt as a method for treatment in subjects in need thereof. The described therapeutic target is expressed as treatment of hyperproliferative disorders, including multiple cancers and brain tumors.
The invention includes defined mesylate salt forms and criteria for their identification, including HT-XRPD characteristic peaks and peak sets. The document further reports physical and chemical stability information for mesylate salt forms under storage conditions and discusses form conversion behavior and chemical stability over time.
Claims Coverage
The provided independent claim covers inhibiting c-Met kinase activity in a subject by administering a therapeutically effective amount of a specific mesylate salt of a triazolopyrazine derivative of formula (1). The independent claim is narrowed by multiple dependent inventive features that specify stereochemistry, HT-XRPD-defined salt identification, and hyperproliferative disorder indications.
Mesylate salt for c-Met kinase inhibition
Administering to a subject in need thereof a therapeutically effective amount of the mesylate salt of a triazolopyrazine derivative of formula (1) to inhibit the activity of c-Met kinase in the subject.
(S) enantiomer mesylate salt
The method uses the (S) enantiomer of the triazolopyrazine derivative of formula (1) as the mesylate salt.
HT-XRPD mesylate salt peak ranges
The mesylate salt is characterized by an HT-XRPD diffraction pattern having characteristic peaks at about 15.5 to 16.0 2θ (deg), about 17.5 to 18.0 2θ (deg), and about 21.5 to 22.0 2θ (deg).
HT-XRPD mesylate salt peak sets with d and intensity
The HT-XRPD (mesylate salt) X-ray powder diffraction pattern has characteristic peaks according to a specified first listed peak set or a specified second listed peak set, including 2θ (deg), d (Å), and intensity values.
Treating hyperproliferative disorder
The method treats a subject who is suffering from a hyperproliferative disorder.
Cancer and brain tumor indications within hyperproliferative disorder
The method treats a hyperproliferative disorder selected from lung cancer, gastric cancer, pancreatic cancer, colon cancer, ovarian cancer, renal cell cancer, prostate cancer, or a brain tumor.
Across the claims provided, the inventive scope is directed to administering a therapeutically effective amount of a mesylate salt of a triazolopyrazine c-Met kinase inhibitor (ABN-401) to inhibit c-Met kinase, with dependent limitations specifying the (S) enantiomer and defining the mesylate salt via HT-XRPD characteristic peaks/peak sets. Further dependent limitations restrict the intended use to hyperproliferative disorders and specifically enumerated cancer types and brain tumors.
Stated Advantages
Improved solubility and/or stability of the drug product while retaining pharmacokinetic/therapeutic effects.
Documented Applications
Inhibiting c-Met kinase in a subject by administering a therapeutically effective amount of a mesylate salt of a triazolopyrazine derivative of formula (1).
Treatment of hyperproliferative disorders in a subject.
Treatment of lung cancer, gastric cancer, pancreatic cancer, colon cancer, ovarian cancer, renal cell cancer, prostate cancer, or a brain tumor as hyperproliferative disorders.
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