Substituted pyrazolo[3,4-b]pyridines as ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) modulators
Inventors
Pinkerton, Anthony • Sergienko, Eduard • Kiyotsuka, Yohei • Kagechika, Katsuji • Kurosaki, Yasunobu • Arai, Yoshikazu • Nagamochi, Masatoshi • Ishibashi, Koutaro
Assignees
Daiichi Sankyo Co Ltd • Sanford Burnham Prebys Medical Discovery Institute
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Publication Number
US-12643910-B2
Publication Date
2026-06-02
Expiration Date
Abstract
Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds of Formula (XI), and methods of using the compounds and compositions comprising the compounds
Core Innovation
The disclosure relates to compounds of Formula (XI), or pharmaceutically acceptable salts thereof. The compounds are defined by substituent variables R30, R31, R32, R34, w, and R35, with Y as CH and R34 as S(O)2NR1A R1A. The structural scope includes optional substitution patterns on phenyl and monocyclic heteroaryl groups, together with allowed substituents such as halogen, CN, alkyl, fluoroalkyl, NR1A R1A, OR1B, and SR1B.
The provided examples characterize substituted heteroaryl compounds within this Formula (XI) space, including pyrazolo[3,4-d]pyrimidine, thieno[3,2-d]pyrimidine, and thieno[2,3-d]pyrimidine derivatives. The examples include benzenesulfonamide and related sulfonamide motifs, aminoalkyl or aminomethyl linkers, piperidine-containing amide, acrylamide, amine, and sulfonamide variants, and variable aryl, heteroaryl, halogen, alkoxy, hydroxyalkyl, and thioether substituents.
The compounds are presented as a broad structural genus with multiple enumerated embodiments and selected compounds from defined groups. Characterization data such as 1H NMR and MS are reported for prepared compounds.
Claims Coverage
Two independent claims are present across the provided items. One independent claim covers compounds of Formula (XI), or pharmaceutically acceptable salts, defined by multiple substituent-variable constraints, and one independent claim covers selection of a specific compound from a defined group or its pharmaceutically acceptable salt.
Formula (XI) compound with defined substituent scope
A compound of Formula (XI), or a pharmaceutically acceptable salt thereof, defined by substituent variables R30, R31, R32, R34, w, and R35, with optional substitution patterns on phenyl and monocyclic heteroaryl groups.
Sulfonamide-linked core with Y fixed as CH
Y is CH and R34 is S(O)2NR1A R1A, with w being 0, 1, 2, or 3 and R35 independently selected from halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, C2-C4 alkynyl, OR1B, or cycloalkyl.
Defined substituent groups R37, R38, and R39
Each R37, R38, and R39 is independently selected from halogen, CN, C1-C4 alkyl, C1-C4 fluoroalkyl, NR1A R1A, OR1B, or SR1B, with R1A and R1B each independently selected from the listed groups.
Selected compound from a defined group
A compound selected from the group consisting of specified compounds, or a pharmaceutically acceptable salt thereof.
Therapeutic treatment of arthritis by administration
A method for treating arthritis in a mammal by administering a therapeutically effective amount of the compound of Formula (XI), or a pharmaceutically acceptable salt thereof, to the mammal in need thereof.
Pharmaceutical composition with specified administration routes
A pharmaceutical composition formulated for administration to a mammal via dermal, inhalation, intravenous, ophthalmic, nasal, oral, or subcutaneous routes.
Claim coverage centers on a Formula (XI) genus with tightly defined substituent variables and optional substitution patterns, together with a separate selection claim for specific compounds from a defined group, and additional claims directed to arthritis treatment and pharmaceutical compositions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating arthritis in a mammal by administering a therapeutically effective amount of the compound of Formula (XI), or a pharmaceutically acceptable salt thereof, to the mammal in need thereof.
Formulating pharmaceutical compositions for administration to a mammal via dermal, inhalation, intravenous, ophthalmic, nasal, oral, or subcutaneous routes.
Treating false gout or pseudogout as part of arthritis treatment in connection with ENPP1 modulation.
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