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US 12,606,537 B2Granted
Thiophene derivatives
AssigneesRyvu Therapeutics S.A., MerckPatent GmbH
InventorsMatthias Leiendecker, Hans-Peter Buchstaller, Thomas Fuchss
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I are inhibitors of HIF-2α, and can be employed for the treatment of diseases such as cancer.
Claims16
A compound of the formula I
- wherein
- R1 denotes A or [C(R6)2]qCyc,
- R2 denotes SO2A,
- R3 denotes H or Hal,
- R4 denotes H or Hal,
- R5 denotes H or Hal,
- R6 denotes H or A′,
- A denotes unbranched or branched alkyl having 1-8 C-atoms, in which 1-5 H atoms may be replaced by OH, O—C1-8-alkyl which alkyl may be unbranched or branched, F, Cl, and/or Br, and/or in which one or two non-adjacent CH2 groups may be replaced by O and/or NH groups,
- A′ denotes unbranched or branched alkyl having 1, 2, 3, or 4 C-atoms,
- Cyc denotes cyclic alkyl with 3, 4, 5, 6, or 7 C-atoms, in which 1-5 H atoms may be replaced by OH, OA, F, and/or Cl,
- Hal denotes F, Cl, Br, or I,
- n denotes 1 or 2,
- m denotes 0, 1, 2, or 3,
- q denotes 0, 1, or 2,
- or a pharmaceutically acceptable solvate, salt, tautomer, or stereoisomer thereof, including a mixture thereof in all ratios.
12 more elements
A compound selected from the group consisting of:
- No.
- Structure
- 1a
- (4S)-1-(cyclohexyloxy)-5,5-difluoro-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 2a
- (4S)-1-(2,2-dimethylpropoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 3a
- (4S)-1-cyclobutoxy-5,5-difluoro-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 4a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(2-methylbutoxy)-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 5a
- (4S)-1-(2,2-difluoroethoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 6a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(3,3,3-trifluoro-2-
- methylpropoxy)-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 7a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(2,2,2-
- trifluoroethoxy)-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 8a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(2-methylpropoxy)-
- 4H,5H,6H-cyclopenta[e]thiophen-4-ol,
- 9a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-{[1,1,1-
- trifluorobutan-2-yl]oxy}-4H,5H,6H-cyclopenta[c]thiophen-
- 4-ol,
- 10a
- (4S)-1-{[1,1-difluoropropan-2-yl]oxy}-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 11a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(3,3,3-
- trifluoropropoxy)-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 12a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-propoxy-4H,5H,6H-
- cyclopenta[c]thiophen-4-ol,
- 13a
- (4S)-1-(cyclopropylmethoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 14a
- (4S)-1-{[1,1-difluoropropan-2-yl]oxy}-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 15a
- (4S)-1-(2,2-difluoropropoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 16a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-[(1-
- methoxycyclobuty])methoxy]-4H,5H,6H-
- cyclopenta[c]thiophen-4-ol,
- 17a
- (4S,5S)-5-fluoro-3-methanesulfonyl-1-(2,2,2-
- trifluoroethoxy)-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 18a
- (4S)-1-[(3,3-difluorocyclobuty])methoxy]-5,5-difluoro-
- 3-methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-
- 4-ol,
- 19a
- (4S)-1-(cyclobutylmethoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 20a
- (4S)-1-(1-cyclobutylethoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 21a
- (4S)-1-(3,3-difluorobutoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 22a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(oxan-4-yloxy)-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 23a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-[2-
- (trifluoromethoxy)ethoxy]-4H,5H,6H-
- cyclopenta[c]thiophen-4-ol,
- 24a
- 1-(3,4-difluorophenoxy)-5,5-difluoro-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 25a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(propan-2-yloxy)-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 26a
- 3-chloro-5-{(4S)-5,5-difluoro-4-hydroxy-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-1-
- yl]oxy}benzonitrile,
- 27a
- (4S)-1-(3,5-difluorophenoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 26a
- 3-{[(4S)-5,5-difluoro-4-hydroxy-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-1-yl]oxy}-5-
- fluorobenzonitrile,
- 29a
- (4S)-5,5-difluoro-1-(4-fluorophenoxy)-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 30a
- (4S)-1-(3-chloro-5-fluorophenoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- 31a
- 3-{[(4S)-5,5-difluoro-4-hydroxy-3-methanesulfonyl-
- 4H,5H,6H-cyclopenta[c]thiophen-1-yl]oxy}benzonitrile,
- 32a
- (4S)-1-ethoxy-5,5-difluoro-3-methanesulfonyl-4H,5H,6H-
- cyclopenta[c]thiophen-4-ol,
- 33a
- (4S)-5,5-difluoro-3-methanesulfonyl-1-(4,4,4-
- trifluorobutoxy)-4H,5H,6H-cyclopenta[c]thiophen-4-ol,
- and
- 34a
- (4S)-1-(3,4-difluorophenoxy)-5,5-difluoro-3-
- methanesulfonyl-4H,5H,6H-cyclopenta[c]thiophen-4-ol;
- or a pharmaceutically acceptable solvate, salt, tautomer or stereoisomer thereof, including a mixture thereof in all ratios.
109 more elements
The method wherein the cancer is a cancer of head, neck, eye, mouth, throat, esophagus, bronchus, larynx, pharynx, chest, bone, lung, colon, rectum, stomach, prostate, urinary bladder, uterine, cervix, breast, ovaries, testicles or other reproductive organs, skin, thyroid, blood, lymph nodes, kidney, liver, pancreas, brain, or central nervous system, or wherein the cancer is a solid tumor, blood-borne tumor, glioblastoma, renal cell carcinoma (RCC), or clear cell renal cell carcinoma (ccRCC).
Dependencies are inferred from the claim text.