Triazine compounds and pharmaceutical use thereof
Inventors
Nagamori, Hironobu • Mitani, Ikuo • Yamashita, Masaki • Hotta, Takahiro • Nakagawa, Yuichi • Ueda, Masatoshi
Assignees
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Publication Number
US-12398111-B2
Publication Date
2025-08-26
Expiration Date
Abstract
Provided is a compound having an mPGES-1 inhibitory activity and useful for the prophylaxis or treatment of pain, rheumatism, osteoarthritis, fever, Alzheimer's disease, multiple sclerosis, arteriosclerosis, glaucoma, ocular hypertension, ischemic retinal disease, systemic scleroderma and cancer including colorectal cancer.A compound represented by the formula [I] or a pharmaceutically acceptable salt thereof: wherein each symbol is as defined in the SPECIFICATION.
Core Innovation
The invention relates to a compound represented by formula [I] or a pharmaceutically acceptable salt thereof, wherein X is CH and ring Cy has a specified formula. The structure includes substituent options for R1, R3, R4, R5, Rc and Rd, with defined chemical group classes including halogen, C1-6 alkyl, cyano, haloC1-4 alkyl, hydroxy, C1-6 alkoxy, aryl, and heteroaryl options.
R3 is selected from halogen, hydroxy, C1-6 alkyl, or —ORc, where Rc is C1-6 alkyl optionally substituted by halogen, hydroxy, C1-6 alkoxy, and —C(O)NRc1Rc2, and may include optionally substituted C6-10 aryl or 5- or 6-membered heteroaryl. R4 is hydrogen, halogen, C1-6 alkyl, or C1-6 alkoxy, and R5 is halogen, hydroxy, C1-6 alkylsulfanyl, C1-6 alkyl, C3-7 cycloalkyl, or —ORd with defined alkynyl, cycloalkyl, alkyl, and saturated heterocyclyl options.
The definition includes m1 as 0, 1, 2 or 3, with independent selection of R5 when m1 is 2 or 3, and an explicit exclusion of 4,6-bis-(2,5-dimethyl-phenyl)-1,3,5-triazin-2-ol. The document also describes mPGES-1 inhibitory agents and positions these compounds as final-step PGE2 biosynthesis inhibitors, with pharmaceutical agents for therapeutic or prophylactic use.
Claims Coverage
The claim coverage centers on one independent compound claim defining formula [I] with multiple constrained substituent variables, plus dependent claims that narrow specific substituent selections and add a method for inhibiting mPGES-1. The independent claim includes an explicit exclusion of a named compound. In total, the inventive features are the defined chemical scaffold, specific substituent restrictions, the m1 positional constraint, the explicit exclusion, and the therapeutic use claim.
Formula [I] compound with substituted ring Cy
A compound represented by the formula [I] or a pharmaceutically acceptable salt thereof, wherein X is CH and ring Cy is defined by the specified formula with constrained substituent positions.
Defined R1 substituent set
R1 is selected from halogen, C1-6 alkyl, cyano, or haloC1-4 alkyl.
Defined R3 substituent set including —ORc
R3 is selected from halogen, hydroxy, C1-6 alkyl, or —ORc, wherein Rc is C1-6 alkyl optionally substituted by halogen, hydroxy, C1-6 alkoxy, and —C(O)NRc1Rc2, and may also include optionally substituted C6-10 aryl or 5- or 6-membered heteroaryl.
Defined R4 substituent set
R4 is selected from hydrogen, halogen, C1-6 alkyl, or C1-6 alkoxy.
Defined R5 substituent set including —ORd
R5 is selected from halogen, hydroxy, C1-6 alkylsulfanyl, C1-6 alkyl, C3-7 cycloalkyl, or —ORd, wherein Rd is C2-6 alkynyl, C3-7 cycloalkyl optionally substituted by C1-6 alkyl, or C1-8 alkyl optionally substituted by halogen, C6-10 aryl, C1-6 alkoxy, and saturated heterocyclyl options.
m1 positional constraint and explicit exclusion
m1 is 0, 1, 2 or 3, and when m1 is 2 or 3, each R5 is selected independently, excluding 4,6-bis-(2,5-dimethyl-phenyl)-1,3,5-triazin-2-ol.
Inhibition of mPGES-1 by administration
A method for inhibiting mPGES-1 by administering a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to a human who needs treatment.
Overall, the claims are directed to a structurally defined formula [I] compound family with constrained substituent sets for R1, R3, R4, R5, Rc and Rd, an m1 positional constraint, and an explicit exclusion of a named compound. Dependent coverage includes narrowing substituent selections and a method claim directed to inhibiting mPGES-1 by administration to a human.
Stated Advantages
Inhibiting mPGES-1.
Provides mPGES-1 inhibitory agents as final-step PGE2 biosynthesis inhibitors.
Provides pharmaceutical agents for therapeutic or prophylactic use.
Documented Applications
Inhibition of mPGES-1 by administering a therapeutically effective amount of the compound to a human who needs treatment.
Treatment or prophylaxis of pain.
Treatment or prophylaxis of inflammatory disorders.
Treatment or prophylaxis of fever.
Treatment or prophylaxis of neurodegenerative disease, including Alzheimer’s disease and multiple sclerosis.
Treatment or prophylaxis of arteriosclerosis/atherosclerosis.
Treatment or prophylaxis of glaucoma and ocular hypertension.
Treatment or prophylaxis of ischemic retinal disease.
Treatment or prophylaxis of systemic scleroderma.
Treatment or prophylaxis of cancer, including colorectal cancer.
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