Ester and carbonate pyrimidine compounds as JAK kinase inhibitors
Inventors
Gerken, Philip A. • Chao, Jianhua • Long, Daniel D.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11845747-B2
Publication Date
2023-12-19
Expiration Date
Abstract
The invention provides compounds of formula (I): or pharmaceutically-acceptable salts thereof, that are inhibitors of Janus kinases and release an active metabolite in vivo. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat inflammatory skin diseases and other diseases.
Core Innovation
The disclosure describes a pharmaceutical composition comprising an ester or carbonate pyrimidine prodrug compound selected from a specified group, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. These compounds inhibit JAK1, JAK2, JAK3, and TYK2 and release active metabolite M in vivo. The compositions encompass topical dosage forms such as creams, ointments, lotions, gels, and foams.
The derivatives demonstrate JAK and TYK2 enzymatic activity and interleukin-2-stimulated cellular activity, alongside skin metabolism and microsomal clearance characteristics. Certain derivatives exhibit substantial conversion to active metabolite M in topical pharmacokinetic testing and high solubility at physiological pH. The disclosure evaluates these compounds for inflammatory and autoimmune conditions while maintaining localized dermal exposure with minimized systemic exposure.
Claims Coverage
The claims define one independent claim directed to one inventive feature covering a pharmaceutical composition.
Pharmaceutical composition comprising a selected compound or salt and carrier
A pharmaceutical composition comprising a compound selected from the group consisting of the compounds specified in the claim, or a pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable carrier.
The claim coverage focuses on a pharmaceutical composition comprising a selected compound or its pharmaceutically acceptable salt with a pharmaceutically-acceptable carrier, with dependent claims further defining additional therapeutic agents, dosage forms, and weight-percentage ranges.
Stated Advantages
The compounds exhibit useful excipient solubility and high pH 7.4 solubility, providing targeted skin exposure with reduced systemic exposure.
Documented Applications
The compositions are documented for inflammatory and autoimmune diseases, particularly atopic dermatitis and alopecia areata, administered via topical dosage forms including lotions, creams, gels, sticks, sprays, ointments, pastes, foams, and mousses.
Interested in licensing this patent?