US2022024917A1PendingUtilityA1
Pyridazinones and methods of use thereof
Est. expirySep 18, 2038(~12.2 yrs left)· nominal 20-yr term from priority
C07D 471/04A61P 35/00A61P 3/04A61P 25/22A61P 25/04A61P 27/02A61P 9/12A61P 25/24A61P 3/10A61P 13/12A61K 31/519A61P 29/00A61P 9/10
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Claims
Abstract
Disclosed are compounds according to Formula (I), and related pharmaceutical compositions. Also disclosed are therapeutic methods, e.g., of treating kidney diseases, using the compounds of Formula (I).
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of structural formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
“---” is a single bond or a double bond
X 1 is CH or N;
when “---” is a double bond, X 2 is CH or N;
when “---” is a single bond, X 2 is N(CH 3 ),
when X 1 is CH, X 2 is N or N(CH 3 );
Y is —O—, —N(CH 3 )—, —N(CH 2 CH 2 OH)—, cyclopropan-1,1-diyl, or —CH(CH 3 )—;
Q is 2-trifluoromethyl-4-fluorophenyl, 2-difluoromethyl-4-fluorophenyl, 2-trifluoromethylphenyl, 2-methyl-4-fluorophenyl, 2-chloro-4-fluorophenyl, 2-chlorophenyl, 1-(benzyl)-4-methylpiperidin-3-yl, 4-trifluoromethylpyridin-3-yl, 2-trifluoromethyl-6-fluorophenyl, 2-trifluoromethyl-3-cyanophenyl, 2-ethyl-3-fluorophenyl, 2-chloro-3-cyanophenyl, 2-trifluoromethyl-5-fluorophenyl, or 2-difluoromethylphenyl;
R 3 is hydrogen, —CH 2 OH, —CH(OH)—CH 2 OH, —NH 2 , —CH(OH)CH 3 , —OCH 3 , or —NH—(CH 2 ) 2 OH; and when “---” is a double bond, R 4 is absent;
and when “---” is a single bond, R 3 and R 4 are taken together to form ═O; and
each of R 5 and R 6 is independently hydrogen or —CH 3 , provided that if X 1 is N, X 2 is N, Y is —O— or —N(CH 3 )—, and Q is 2-trifluoromethylphenyl, then at least one of R 3 , R 5 , and R 6 is not hydrogen.
2 . The compound of claim 1 , represented by structural formula II:
or a pharmaceutically acceptable salt thereof; wherein:
R 1 is chloro, —CF 3 , —CHF 2 , or —CH 3 ;
R 2 is hydrogen or fluoro; and
R 3 is hydrogen, —NH 2 , —CH 2 OH, or CH(OH)—CH 2 OH.
3 . The compound of claim 2 , wherein when R 1 is —CHF 2 , R 2 is not hydrogen.
4 . The compound of claim 1 , selected from any one of the following compounds, or a pharmaceutically acceptable salt thereof:
Com-
pound
Structure
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5 . The compound of claim 4 , selected from any one of the following compounds, or a pharmaceutically acceptable salt thereof:
Compound
Structure
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6 . The compound of claim 5 , selected from any one of the following compounds, or a pharmaceutically acceptable salt thereof:
Compound
Structure
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7 . A pharmaceutical composition comprising a compound of claim 1 ; and a pharmaceutically acceptable carrier.
8 . A method of treating, or the reducing risk of developing, a disease or condition selected from kidney disease, pulmonary arterial hypertension, anxiety, depression, cancer, diabetic retinopathy, or pain, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
9 . The method of claim 8 , wherein the disease or condition is kidney disease selected from Focal Segmental Glomerulosclerosis (FSGS), Diabetic nephropathy, Alport syndrome, hypertensive kidney disease, nephrotic syndrome, steroid-resistant nephrotic syndrome, minimal change disease, membranous nephropathy, idiopathic membranous nephropathy, membranoproliferative glomerulonephritis (MPGN), immune complex-mediated MPGN, complement-mediated MPGN, Lupus nephritis, postinfectious glomerulonephritis, thin basement membrane disease, mesangial proliferative glomerulonephritis, amyloidosis (primary), c1q nephropathy, rapidly progressive GN, anti-GBM disease, C3 glomerulonephritis, hypertensive nephrosclerosis, or IgA nephropathy.
10 . The method of claim 9 , wherein the kidney disease is proteinuric kidney disease.
11 . The method of claim 9 , wherein the kidney disease is microalbuminuria or macroalbuminuria kidney disease.
12 . The method of claim 8 , wherein the disease or condition to be treated is pulmonary arterial hypertension.
13 . The method of claim 8 , wherein the disease or condition to be treated is pain selected from neuropathic pain, and visceral pain.
14 . The method of claim 8 , wherein the disease or condition is cancer selected from chemoresistant breast carcinoma, adriamycin-resistant breast cancer, chemoresistant colorectal cancer, medulloblastoma, and tumor angiogenesis.
15 . The method of claim 8 , wherein the disease or condition is transplant-related FSGS, transplant-related nephrotic syndrome, transplant-related proteinuria, cholestatic liver disease, polycystic kidney disease, autosomal dominant polycystic kidney disease (ADPKD), obesity, insulin resistance, Type II diabetes, prediabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), or non-alcoholic steatohepatitis (NASH).
16 . The method of claim 8 , wherein the subject is a human.Join the waitlist — get patent alerts
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