- Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists
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The nuclear receptor RORγ plays a central role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including TH17 cells. RORγ-dependent inflammation has been implicated in the pathogenesis of several major autoimmune diseases and thus RORγ is an attractive target for therapeutic intervention in these diseases. Starting from a lead biaryl compound 4a, replacement of the head phenyl moiety with a substituted aminopyrazole group resulted in a series with improved physical properties. Further SAR exploration led to analogues (e.g., 4j and 5m) as potent RORγ inverse agonists.
- Wang, Tao,Banerjee, Daliya,Bohnert, Tonika,Chao, Jianhua,Enyedy, Istvan,Fontenot, Jason,Guertin, Kevin,Jones, Howard,Lin, Edward Y.,Marcotte, Douglas,Talreja, Tina,Van Vloten, Kurt
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Read Online
- COMPOUNDS
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The invention relates to novel compounds for use as inhibitors of NLRP3 inflammasone production, wherein such compounds are as defined by compounds of formula (I) and wherein the integers R1, R2 and R3 are defined in the description, and where the compounds may be useful as medicaments, for instance for use in the treatment of a disease or disorder that is associated with NLRP3 inflammasome activity.
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Page/Page column 52; 137
(2021/12/08)
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- NOVEL PROCESSES
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The present invention relates to processes of preparing N- ((1,2,3,4,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H- pyrazole-3-sulfonamide and salts thereof. The present invention further relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.
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Page/Page column 19-20
(2020/05/21)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula A, or a pharmaceutically acceptable salt thereof, are featured (Formula A) or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.
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Page/Page column 265-266
(2020/06/10)
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- NLRP3 INHIBITORS
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The present application relates to compounds with NLRP3inhibitory activity and to associated salts, solvates, prodrugs and pharmaceutical compositions. The present application further relates to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3inhibition.
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Page/Page column 68-69
(2020/06/10)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured.The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.
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Page/Page column 439-440
(2019/02/13)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured. The variables shown in Formula AA are as defined in the claims. The compounds of formula AA are NLRP3 activity modulators and, as such, can be used in the treatment of metabolic disorders (e.g. Type 2 diabetes, atherosclerosis, obesity or gout), a disease of the central nervous system (e.g. Alzheimer's disease, multiple sclerosis, Amyotrophic Lateral Sclerosis or Parkinson's disease), lung disease (e.g. asthma, COPD or pulmonary idiopathic fibrosis), liver disease (e.g. NASH syndrome, viral hepatitis or cirrhosis), pancreatic disease (e.g. acute pancreatitis or chronic pancreatitis), kidney disease (e.g. acute kidney injury or chronic kidney injury), intestinal disease (e.g. Crohn's disease or Ulcerative Colitis), skin disease (e.g. psoriasis), musculoskeletal disease (e.g. scleroderma), a vessel disorder (e.g. giant cell arteritis), a disorder of the bones (e.g. osteoarthritis, osteoporosis or osteopetrosis disorders), eye disease (e.g. glaucoma or macular degeneration), a disease caused by viral infection (e.g. HIV or AIDS), an autoimmune disease (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus or Autoimmune Thyroiditis), cancer or aging.
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Page/Page column 432
(2019/02/13)
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- SULPHONAMIDES AND COMPOSITIONS THEREOF FOR TREATING CONDITIONS ASSOCIATED WITH NLRP ACTIVITY
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In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured: wherein the variables shown in Formula AA can be as defined anywhere herein. Compounds AA are modulators of NLRP1 and/or NLRP3
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Page/Page column 447; 448
(2019/05/10)
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- TRI-SUBSTITUTED IMIDAZOLES FOR THE INHIBITION OF TGF BETA AND METHODS OF TREATMENT
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Pharmaceutical compounds, their methods of manufacture, and methods of treatment of mammals with pharmaceutical compounds are provided.
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Paragraph 0087
(2019/01/17)
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- NOVEL COMPOUNDS
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The present invention relates to compounds of formula (I): comprising a 5-membered nitrogen-containing heteroaryl ring A, wherein the heteroaryl ring A is substituted with at least one group containing an oxygen atom, and wherein said oxygen atom is attached to the heteroaryl ring A via at least two other atoms. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the inhibition of NLRP3.
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Page/Page column 103
(2019/09/18)
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- NOVEL COMPOUNDS
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The present invention relates to substituted 5-membered nitrogen containing heteroaryl compounds, such as sulfonyl triazoles, where the heteroaryl ring is further substituted, optionally via a linking group such as -NH-, with a cyclic group which in turn is substituted at the α-position. The present invention further relates to associated salts, solvates, prodrugs and pharmaceutical compositions, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.
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Page/Page column 162; 163
(2019/11/19)
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- Regioselective Synthesis, NMR, and Crystallographic Analysis of N1-Substituted Pyrazoles
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A systematic study of the N-substitution reactions of 3-substituted pyrazoles under basic conditions has been undertaken. Regioselective N1-alkylation, -arylation, and -heteroarylation of 3-substituted pyrazoles have been achieved using K2CO3-DMSO. The regioselectivity is justified by the DFT calculations at the B3LYP/6-31G??(d) level. A consistent steric effect on chemical shift has been observed for N-alkyl pyrazole analogues. Twenty-five X-ray crystallographic structures have been obtained to confirm the regiochemistry of the major products.
- Huang, Adrian,Wo, Kellie,Lee, So Yeun Christine,Kneitschel, Nika,Chang, Jennifer,Zhu, Kathleen,Mello, Tatsiana,Bancroft, Laura,Norman, Natalie J.,Zheng, Shao-Liang
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p. 8864 - 8872
(2017/09/11)
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- Pyrazole glucokinase activators
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Disclosed herein are pyrazole glucokinase activators of the formula (I) useful for the treatment of metabolic diseases and disorders, preferably diabetes mellitus.
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Page/Page column 55
(2008/06/13)
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