Prodrugs of itaconate and methyl itaconate
Inventors
SLUSHER, BARBARA • Islam, Mohameed • RAIS, RANA • Garza, Luis • Bell, Benjamin • Majer, Pavel • Tenora, Lukas • SNAJDR, Ivan • Krecmerova, Marcela
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Assignees
Institute of Organic Chemistry and Biochemistry of ASCR vvi
MemberJohns Hopkins UniversityJohns Hopkins UniversityFounded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Founded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Publication Number
US-12643846-B2
Publication Date
2026-06-02
Expiration Date
Abstract
Prodrugs of itaconic acid and 1- and 4-methyl itaconic acid and their use for treating a disease, disorder, or condition associated with inflammation are disclosed.
Core Innovation
The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. The compounds are characterized by substituent variables R1 and R2, where R1 and R2 are selected from specified combinations including OH and O-C1-6 alkyl, and other options that include an integer-defined substitution pattern. The integer parameters u, n, and in one option m and p are restricted to limited ranges.
Further embodiments define additional constrained substituents beyond R1 and R2, including selections such as R4 being O-C1-6 alkyl, R21 being O-C1-6 alkyl, and R6 being CH3, together with constrained integer parameters. The defined structural combinations cover multiple alternative patterns of O-alkyl substitution as part of the formula (I) compound definitions.
The related set of depicted structures supports multiple named compounds and analogs including 4-MI, LTP-1025, Itaconate, MK-933, MK-937, MK-939, MK-944, MK-945, and 1-MI and 4-MI labeled structures. The structures show substituted aromatic or cyclic cores bearing amide/urea-like nitrogen substituents and ester/ether-linked itaconate moieties, including variants with different alkyl substituents and different itaconate side-chain connectivity patterns.
Claims Coverage
The partial content includes one independent claim. It covers a compound of formula (I) or a pharmaceutically acceptable salt with R1 and R2 restricted to specified structural combinations involving O-C1-6 alkyl groups and limited integer ranges u, n, and in one option m and p, including an option where R2 is an O-C1-6 unsubstituted alkyl.
Compound of formula (I) with restricted R1 and R2 combinations
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are selected from the specified combinations (a)-(g) with integer parameters u (1-4) and n (1-4), and in option (g) additional parameters m (1-4) and p (1-20), and where the substituents are limited to OH, H, O-C1-6 alkyl, and in option (g) CH3 and O-C1-6 unsubstituted alkyl.
The claim coverage is centered on a formula (I) compound or pharmaceutically acceptable salt with R1/R2 restricted to enumerated O-C1-6 alkyl, OH, and H patterns and constrained integer ranges, including a broader option (g) that further limits R6 to CH3 and p to 1-20.
Stated Advantages
Improved pharmacokinetics and cell permeation are implicitly addressed by the prodrug design to overcome charged itaconate limitations.
Exhibits anti-inflammatory effects via itaconate activity, including succinate dehydrogenase inhibition and NRF2-dependent antioxidant responses.
Plasma stability and plasma release of active itaconate and/or monomethyl itaconate are described through referenced figures.
Documented Applications
Treating inflammation-associated diseases or inflammation-associated conditions by administering the compound of formula (I) or a pharmaceutical composition.
Anti-inflammatory effects are noted in keratinocytes.
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