Hydroxytriazine compounds and pharmaceutical use thereof

Inventors

Mitani, Ikuo • Hirono, Yutaro • Yamashita, Masaki

Assignees

Shionogi and Co Ltd

Abstract

The present invention provides 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/or cancer including colorectal cancer.The present invention relates to a compound of formula [I-a], [I-b] or [I-c] or a pharmaceutically acceptable salt thereof:wherein each symbol is as defined in the specification.

Core Innovation

The patent describes hydroxytriazine mPGES-1 inhibitor compounds of formula [I-c] and pharmaceutically acceptable salts thereof. The compounds are defined by substituent-variable definitions including R1, R2, R3/R4/R5/R6, X, and n, with fixed selections such as R2 being hydrogen and R6 being 1-methylbutyl or n-hexyl. The disclosure identifies a preferred embodiment corresponding to [I-c] and provides dependent embodiments by further narrowing substituent selections.

The invention relates to substituted triazine-based compounds of formula [I-a], [I-b], and [I-c], including compound [I-c] and pharmaceutically acceptable salts thereof. The description presents synthetic routes that build the substituted triazine scaffold through boronation and Suzuki coupling, conversion of hydroxyl to amino via azidation and reduction, amide bond formation, and functional-group interconversions. Example preparations are provided for intermediates and final products, including an amide product and related hydroxy analogs.

The documents also describe substituted fused heteroaromatic carboxylic acid compounds having a common heterocycle/diaryl-carboxylic acid scaffold with a carboxylic acid (OH). The illustrated structures include a chloro-substituted aryl portion, a fused N-containing ring system, and varying substituents on the aromatic rings, including alkoxy groups, alkyl and alkenyl-type variations, and multiple fluorinated stereocenters. The examples include compounds defined by the formula [I-c] or pharmaceutically acceptable salts thereof, with substituent groups R selected from defined alkyl, fluoroalkyl, fluoro, alkoxy, and alkoxy-alkyl options, including fluoro-containing motifs such as trifluoromethyl and difluoromethyl variants.

Claims Coverage

The independent claims provided define a specific hydroxytriazine compound of formula [I-c] or a pharmaceutically acceptable salt thereof, a pharmaceutical composition including the compound with a pharmaceutically acceptable carrier, and a treatment method by administering a therapeutically effective amount to a human for specified indications. The principal inventive features center on the defined compound structure and its use in pharmaceutical composition and treatment claims.

Overall, the claim coverage centers on a structurally defined mPGES-1 inhibitor compound of formula [I-c] with fixed and constrained substituent selections, and extends that compound into a pharmaceutical composition and into treating pain and the listed diseases in a human by administration of a therapeutically effective amount.

Stated Advantages

Documented Applications