Method of inhibiting kinase by camsylate salts of triazolopyrazine derivatives
Inventors
Choi, Jun Young • PARK, Kyung-eui • Kim, Na Young
Assignees
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Publication Number
US-12275740-B2
Publication Date
2025-04-15
Expiration Date
Abstract
Disclosed are a salt (camsylate salt) of D(+)-10-camphorsulfonic acid and a triazolopyrazine derivative of formula (1), pharmaceutical compositions thereof, methods of making the salt, and therapeutic use thereof:
Core Innovation
The invention relates to camsylate salts of a (S) triazolopyrazine derivative identified as ABN-401, where the compound is represented by formula (1). The camsylate salts use D(+)-10-camphorsulfonic acid as the counterion, producing specific solid salt forms referred to as Camp1, Camp2, and Camp4. These salt forms are characterized by an HT-XRPD pattern with characteristic peaks and by multiple complementary analytical techniques.
A key aspect is providing camsylate salts with improved salt-form properties while retaining free-base pharmacokinetics. The description links the selected salt forms to measurable physical and chemical stability, including long-term and accelerated ageing observations that are used to evidence stability and interconversion behavior among forms. Polymorph screening and thermocycling are described in connection with form interconversions such as Camp2 ↔ Camp4.
The camsylate salts are also used in pharmaceutical compositions and as c-Met kinase inhibition agents. The described approach supports inhibiting the activity of c-Met kinase by administering a therapeutically effective amount of a camsylate salt of the compound of formula (1) to a subject in need thereof.
Claims Coverage
The relevant claim set is centered on one independent claim that covers a method of inhibiting c-Met kinase by administering a therapeutically effective amount of a camsylate salt defined by an HT-XRPD pattern. Dependent claims add three main refinement axes: stereochemistry, a narrower subject condition, and further narrowing of that condition to specified cancer types or a brain tumor. Across the claims, the inventive features total three to four groups depending on how the refinement categories are grouped.
c-Met kinase inhibition by HT-XRPD-defined camsylate salt administration
Administering to a subject in need thereof a therapeutically effective amount of a camsylate salt of the compound of formula (1) for inhibiting the activity of c-Met kinase, where the camsylate salt has an HT-XRPD pattern with characteristic peaks corresponding substantially to specified 2θ peak positions and intensities.
(S) enantiomer in the formula (1) compound
The method further comprises that the compound of formula (1) comprises the (S) enantiomer.
HT-XRPD peak-range constraint at about 14–14.5° and about 16–17° 2θ
The HT-XRPD pattern of the camsylate salt includes characteristic peaks corresponding substantially to about 14 to 14.5° 2θ and about 16 to 17° 2θ.
Treatment for a hyperproliferative disorder subject
Administering the therapeutically effective amount to a subject who is suffering from a hyperproliferative disorder.
Hyperproliferative disorder selected from specified cancers and brain tumor
The hyperproliferative disorder is selected from lung cancer, gastric cancer, pancreatic cancer, colorectal cancer, ovarian cancer, renal cell cancer, prostate cancer, liver cancer, breast cancer, or a brain tumor.
Claim coverage focuses on c-Met kinase inhibition using an administered camsylate salt of formula (1) defined by an HT-XRPD characteristic-peak pattern, with refinements specifying the (S) enantiomer, constraining HT-XRPD peak ranges, and narrowing the treated subject to hyperproliferative disorders including specified cancer types or a brain tumor.
Stated Advantages
Improved salt-form properties (solubility/stability) while retaining free-base pharmacokinetics.
Documented Applications
Inhibiting the activity of c-Met kinase in a subject by administering a therapeutically effective amount of a camsylate salt of the compound of formula (1).
Treatment of a subject suffering from a hyperproliferative disorder, including lung cancer, gastric cancer, pancreatic cancer, colorectal cancer, ovarian cancer, renal cell cancer, prostate cancer, liver cancer, breast cancer, or a brain tumor.
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