CN-118638081-B - Sulfonylurea compounds

Abstract

The present application relates to sulfonylurea compounds, in particular to compounds having both sulfonylurea and 2- (furan-2 yl) propan-2-ol, and to related salts, solvates, prodrugs and compositions. The application also relates to the pharmaceutical use of said compounds as a treatment and prophylaxis of medical conditions and diseases by NLRP3 inhibition. The application also relates to the pharmaceutical use of said compounds as a treatment and prophylaxis of medical conditions and diseases by NLRP3 inhibition. The sulfonylurea compound has strong NLRP3 inflammation small body inhibition activity.

Inventors

• MIN ZHENLI
• LI XUANPING
• ZHENG PENG
• LIU JINGLONG

Assignees

• 武汉科技大学

Dates

Publication Date

20260508

Application Date

20240523

Claims (3)

1. 1. A compound or a pharmaceutically acceptable salt thereof, wherein the compound has the structural formula: 。
2. 2. a compound or a pharmaceutically acceptable salt thereof, wherein the compound has the structural formula: 。
3. 3. Use of a compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of a NLRP3 inflammatory small-scale related disease.

Description

Sulfonylurea compounds Technical Field The present application relates to sulfonylurea compounds, in particular to compounds having both a sulfonylurea structure and a 2- (furan-2 yl) propan-2-ol structure, and to related salts, solvates, prodrugs and compositions. The application also relates to the pharmaceutical use of said compounds as inhibitors of NLRP3 for the treatment and prophylaxis of medical conditions and diseases. Background Nucleotide binding oligomerization structure-like receptor protein3 (Nucleoteide-bindingoligomerizationdomain-likereceptorprotein, NLRP 3) forms a complex protein macromolecule with the linker protein ASC (ApoptosisassociatedSpeck-likeproteincontainingCaspaserecruitmentdomain) and the effector protein pro-caspase-1, the NLRP3 inflammatory minibody. NLRP3 inflammatory corpuscles mediate inflammatory responses by recognizing pathogenic related molecules such as exogenous pathogenic microorganisms, bacteria and the like or endogenous injury related molecular patterns, and the normal biological activity plays an important role in maintaining homeostasis of the organism. However, for a number of pathological reasons, NLRP3 inflammatory corpuscles, when overactivated, can cause excessive release of the inflammatory mediators interleukin-1 beta and interleukin-18, which can cause severe inflammation in cells. At the same time, the perforating protein GASDERMIND is cleaved by it, which in turn leads to cell death, exacerbating the development of inflammation. Studies have shown that aberrant activation of NLRP3 inflammasome is closely related to the development of various diseases such as autoimmune diseases such as inflammatory enteritis, rheumatoid arthritis, etc., atherosclerosis, gout, type 2 diabetes, ischemic stroke, and neurodegenerative diseases such as alzheimer's disease and parkinson's disease, and other related diseases. NLRP3 inflammatory corpuscles play an important role in diseases related to inflammatory reaction, and inhibiting the activity of the inflammatory corpuscles plays a role in treating the related diseases. Given the broad and serious hazards of NLRP3 inflammatory body-related diseases, there is an urgent need for excellent performance NLRP3 inflammatory body inhibitors. Disclosure of Invention The present application relates to sulfonylurea compounds, in particular to compounds having both sulfonylurea and 2- (furan-2 yl) propan-2-ol, and to related salts, solvates, prodrugs and compositions. The application also relates to the pharmaceutical use of said compounds as a treatment and prophylaxis of medical conditions and diseases by NLRP3 inhibition. The sulfonylurea compound has strong NLRP3 inflammation small body inhibition activity. Therefore, the embodiment of the application at least shares the following technical scheme: In a first aspect, the examples disclose compounds of formula (I): Wherein A is phenyl, B is a condensed ring aromatic hydrocarbon group, R 1 is independently selected from H, alkyl, halogen, haloalkyl, alkoxy, R 2 is independently selected from H, alkyl, halogen, haloalkyl, alkoxy, R 3 is independently selected from H or halogen. In a second aspect, embodiments disclose pharmaceutically acceptable salts, solvates or prodrugs of the compounds of the first aspect. In a third aspect, embodiments disclose an NLRP3 inhibitor comprising a compound of the first aspect, or a pharmaceutically acceptable salt of the second aspect, or a solvate or prodrug thereof. In a fourth aspect, embodiments disclose a composition. The composition comprises a compound according to the first aspect, or an optical isomer, a labeled compound, a pharmaceutically acceptable salt, tautomer, solvate, or prodrug according to the second aspect, and a pharmaceutically acceptable excipient. In a fifth aspect, the embodiments disclose a composition. The composition consists of a compound of the first aspect, an optical isomer, a labeled compound, a pharmaceutically acceptable salt, tautomer, solvate, or prodrug of the second aspect, the compound, the pharmaceutically acceptable salt, solvate, or prodrug, or the composition for use in a medicament. In a sixth aspect, embodiments disclose the use of a compound of the first aspect, or a pharmaceutically acceptable salt of the second aspect, or a solvate or prodrug thereof, or a composition of the fourth aspect, for the manufacture of a medicament for the treatment or prevention of a disease, disorder or condition selected from the group consisting of: (i) Inflammation; (ii) Autoimmune disease; (iii) Cancer; (iv) Infection; (v) Diseases of the central nervous system; (vi) Metabolic diseases; (vii) Cardiovascular disease; (viii) Respiratory disease; (ix) Liver disease; (x) Kidney disease; (xi) An eye disease; (xii) Skin diseases; (xiii) A lymphatic disorder; (xiv) Psychological disorders; (xv) Graft versus host disease; (xvi) Pain feeling in touch, and (Xvii) It has been determined that individuals carry any disease in