Therapeutic agent for inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases
Inventors
ISHIDA, Natsuki • Tabata, Yuji • Matsuhira, Takashi • Tamura, Keiji • Yamakawa, Takeru • ISSHIKI, Satoshi • Wakiyama, Yoshinari • OUCHI, Shohei
Assignees
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Publication Number
US-12239643-B2
Publication Date
2025-03-04
Expiration Date
Abstract
A therapeutic agent for treating at least one disease selected from the group consisting of inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases, comprising: at least one selected from the group consisting of a compound represented by the following general formula (1) and pharmacologically acceptable salts thereof as an active ingredient.[In the formula (1), R1 and R2 may be the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group et al.; R3 represents a hydrogen atom; R4 represents an optionally substituted 4- to 10-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from an oxygen atom, a nitrogen atom, and a sulfur atom; X represents a group represented by the following formula: —CH2—, —CH2—CH2—, —CH2—CH2—CH2—, or —CH2—O—CH2—; and Z represents a hydrogen atom or a hydroxyl group.]
Core Innovation
The invention relates to a therapeutic agent for treating at least one disease selected from inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases. The therapeutic agent comprises at least one compound represented by general formula (1) and pharmacologically acceptable salts thereof as an active ingredient. The compounds of general formula (1) are defined by substituents R1, R2, R3, R4, X, and Z with broad options for the substituent framework.
In general formula (1), R3 represents a hydrogen atom, R4 represents an optionally substituted 4- to 10-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, X is defined by specific methylene or methylene-oxy linkage patterns, and Z is a hydrogen atom or a hydroxyl group. The disclosed examples include benzo[d]oxazole derivatives bearing diazabicyclic or oxa-diazabicyclic amine moieties and thiazol-2-yl or related heteroaryl groups, with varied substituent embodiments.
The compounds represented by general formula (1) are described as PDE4 inhibitory compounds and are used as therapeutic agents for treating disease states. The description further includes a narrower alternative general formula (11), dependent structural refinements for R1 and R2, and a potency requirement expressed as PDE4 inhibition with an IC50 of 11 nM or less for 50% inhibition of PDE4 activity.
Claims Coverage
The consolidated claim coverage centers on a therapeutic-agent claim directed to compounds of general formula (1) or pharmacologically acceptable salts for treating inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases. The inventive features repeated across the inputs comprise the general formula (1) scaffold, substituent definitions for R1, R2, R3, R4, X, and Z, a narrower general formula (11) subset, and a PDE4 inhibitory potency threshold, with R2 fixed to hydrogen in one scope.
Therapeutic agent for inflammatory, autoimmune, fibrotic, and cancer diseases
A therapeutic agent for treating at least one disease selected from inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases, comprising at least one compound represented by general formula (1) and pharmacologically acceptable salts thereof as an active ingredient.
General formula (1) substituent framework
The compound represented by general formula (1) defines R1 and R2 by broad substituent options, R3 as a hydrogen atom, R4 as an optionally substituted 4- to 10-membered monocyclic heterocyclic group containing 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur, X as a defined methylene or methylene-oxy linkage, and Z as a hydrogen atom or a hydroxyl group.
Alternative general formula (11)
The therapeutic agent includes a compound represented by general formula (1) that is a compound represented by general formula (11), with R1, R2, and X constrained by specified substituent options.
PDE4 inhibitory activity threshold
The therapeutic agent is defined by PDE4 inhibitory activity of at least one selected compound represented by general formula (1) or pharmacologically acceptable salts thereof, having an IC50 of 11 nM or less for 50% inhibition of PDE4 activity.
R2 fixed to hydrogen
The compound represented by general formula (1) has R1 selected from specified functional groups and ring/heterocycle substituents, and R2 is hydrogen atom.
The claim coverage is unified around therapeutic agents based on general formula (1) compounds, with repeated structural refinements to R1 and R2, an alternative general formula (11) subset, and a PDE4 inhibitory potency requirement.
Stated Advantages
PDE4 inhibitory activity with an IC50 of 11 nM or less for 50% inhibition of PDE4 activity.
Allows use of pharmacologically acceptable salts of compounds represented by general formula (1) as active ingredients.
Supports therapeutic use for treating inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases.
Superior activity and therapeutic utility across inflammatory, autoimmune, fibrotic, and cancer indications for selected examples, notably Example 248.
Documented Applications
Therapeutic use for treating inflammatory diseases, autoimmune diseases, fibrotic diseases, and cancer diseases.
PDE4-inhibitory therapeutic agent use.
PDE4 inhibition testing, cytokine suppression (including TNFα and IL-17A and other listed interleukins), TGF-β inhibition, antitumor activity, and multiple in vivo inflammatory, autoimmune, and fibrosis model assays.
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