CA2642650C - Novel heterocyclic diphenyl ethers - Google Patents
Novel heterocyclic diphenyl ethers Download PDFInfo
- Publication number
- CA2642650C CA2642650C CA2642650A CA2642650A CA2642650C CA 2642650 C CA2642650 C CA 2642650C CA 2642650 A CA2642650 A CA 2642650A CA 2642650 A CA2642650 A CA 2642650A CA 2642650 C CA2642650 C CA 2642650C
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- compound
- stereoisomer
- hydrate
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 heterocyclic diphenyl ethers Chemical class 0.000 title claims description 32
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 150000003839 salts Chemical class 0.000 claims abstract description 77
- 239000012453 solvate Substances 0.000 claims abstract description 74
- 239000000203 mixture Substances 0.000 claims abstract description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 23
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 21
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 19
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 18
- 206010061218 Inflammation Diseases 0.000 claims abstract description 18
- 239000008103 glucose Substances 0.000 claims abstract description 18
- 230000004054 inflammatory process Effects 0.000 claims abstract description 18
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 16
- 208000035475 disorder Diseases 0.000 claims abstract description 13
- 208000026278 immune system disease Diseases 0.000 claims abstract description 13
- 208000008589 Obesity Diseases 0.000 claims abstract description 12
- 235000020824 obesity Nutrition 0.000 claims abstract description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 11
- 235000021588 free fatty acids Nutrition 0.000 claims abstract description 10
- 150000004677 hydrates Chemical class 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 13
- 150000002500 ions Chemical class 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 239000000443 aerosol Substances 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 235000001727 glucose Nutrition 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000036470 plasma concentration Effects 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 159000000003 magnesium salts Chemical class 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- ONXSZFPCOKFCNR-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-fluorophenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C(=C1)F)=CC=C1CC1C(=O)NC(=O)S1 ONXSZFPCOKFCNR-UHFFFAOYSA-N 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 150000003626 triacylglycerols Chemical class 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- VBCIBLUDWOQXTK-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 VBCIBLUDWOQXTK-UHFFFAOYSA-N 0.000 claims 2
- KRCXWINWQAFOKB-UHFFFAOYSA-L disodium 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]acetate Chemical compound [Na+].[Na+].[O-]C(=O)Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1.[O-]C(=O)Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1 KRCXWINWQAFOKB-UHFFFAOYSA-L 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- BHGTZFWDUYZUMX-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C(=C1)C(F)(F)F)=CC=C1CC1C(=O)NC(=O)S1 BHGTZFWDUYZUMX-UHFFFAOYSA-N 0.000 claims 1
- PAIZTWWKQQRGAM-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxyphenoxy]phenyl]acetic acid Chemical compound C=1C=C(OC=2C=CC(CC(O)=O)=CC=2)C(OC)=CC=1CC1SC(=O)NC1=O PAIZTWWKQQRGAM-UHFFFAOYSA-N 0.000 claims 1
- RKCQQCKSCYBFGA-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-3-fluorophenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C=C1F)=CC=C1CC1C(=O)NC(=O)S1 RKCQQCKSCYBFGA-UHFFFAOYSA-N 0.000 claims 1
- IAVXQVOUTHYEQQ-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-n-methylanilino]phenyl]acetic acid Chemical compound C=1C=C(CC(O)=O)C=CC=1N(C)C(C=C1)=CC=C1CC1SC(=O)NC1=O IAVXQVOUTHYEQQ-UHFFFAOYSA-N 0.000 claims 1
- OWEQNHZUOXAAMY-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]-2-fluorophenyl]acetic acid Chemical compound C1=C(F)C(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 OWEQNHZUOXAAMY-UHFFFAOYSA-N 0.000 claims 1
- JVLKBYPXCUMJPX-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]-n,n-dimethylacetamide Chemical compound C1=CC(CC(=O)N(C)C)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 JVLKBYPXCUMJPX-UHFFFAOYSA-N 0.000 claims 1
- GVUYKUAZFPFMEM-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]butanoic acid Chemical compound C1=CC(C(C(O)=O)CC)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GVUYKUAZFPFMEM-UHFFFAOYSA-N 0.000 claims 1
- MEJBANGHCJDFPZ-UHFFFAOYSA-N 2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=O)S1 MEJBANGHCJDFPZ-UHFFFAOYSA-N 0.000 claims 1
- NOSGARZMOTXNBD-UHFFFAOYSA-N 2-[4-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C(=C1)C(F)(F)F)=CC=C1CC1C(=O)NC(=S)S1 NOSGARZMOTXNBD-UHFFFAOYSA-N 0.000 claims 1
- MYYCPWQESUXLMF-UHFFFAOYSA-N 2-[4-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=S)S1 MYYCPWQESUXLMF-UHFFFAOYSA-N 0.000 claims 1
- LZGPALLAOQVAGB-UHFFFAOYSA-N 2-[4-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]phenoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1C=C1C(=O)NC(=S)S1 LZGPALLAOQVAGB-UHFFFAOYSA-N 0.000 claims 1
- ZYKLVVRPCTYYEF-UHFFFAOYSA-N 2-[4-[4-[[3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl]methyl]-3-fluorophenoxy]phenyl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1CC(C(=C1)F)=CC=C1OC1=CC=C(CC(O)=O)C=C1 ZYKLVVRPCTYYEF-UHFFFAOYSA-N 0.000 claims 1
- RGXFSXSMGFQJSF-UHFFFAOYSA-N 2-[4-[4-[[3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl]phenoxy]phenyl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1=CC(C=C1)=CC=C1OC1=CC=C(CC(O)=O)C=C1 RGXFSXSMGFQJSF-UHFFFAOYSA-N 0.000 claims 1
- UKIFBTLFPXEAME-UHFFFAOYSA-N 2-[6-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]pyridin-3-yl]acetic acid Chemical compound N1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 UKIFBTLFPXEAME-UHFFFAOYSA-N 0.000 claims 1
- DGKPTWMXFRSFRZ-UHFFFAOYSA-N 2-[6-[4-[(2-oxo-1,3-dihydroindol-3-yl)methyl]phenoxy]pyridin-3-yl]acetic acid Chemical compound N1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C2=CC=CC=C2NC1=O DGKPTWMXFRSFRZ-UHFFFAOYSA-N 0.000 claims 1
- IJXFNIRTLPJNSV-UHFFFAOYSA-N 2-[6-[4-[(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl)methyl]phenoxy]pyridin-3-yl]acetic acid Chemical compound N1=CC(CC(=O)O)=CC=C1OC(C=C1)=CC=C1CC1C(=O)NC(=S)S1 IJXFNIRTLPJNSV-UHFFFAOYSA-N 0.000 claims 1
- XRAQRDBRFHRLBY-UHFFFAOYSA-N 2-[6-[4-[[3-(carboxymethyl)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-yl]methyl]phenoxy]pyridin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=S)SC1CC(C=C1)=CC=C1OC1=CC=C(CC(O)=O)C=N1 XRAQRDBRFHRLBY-UHFFFAOYSA-N 0.000 claims 1
- ISYRHWPKMFUVBV-UHFFFAOYSA-N 5-[[4-[4-(2-oxo-2-piperazin-1-ylethyl)phenoxy]-3-(trifluoromethyl)phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C=1C=C(OC=2C=CC(CC(=O)N3CCNCC3)=CC=2)C(C(F)(F)F)=CC=1CC1SC(=O)NC1=O ISYRHWPKMFUVBV-UHFFFAOYSA-N 0.000 claims 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
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- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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| US11/359,657 | 2006-02-21 | ||
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| PCT/US2007/004007 WO2007097992A2 (en) | 2006-02-21 | 2007-02-15 | Novel heterocyclic diphenyl ethers |
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| CA2642650A1 CA2642650A1 (en) | 2007-08-30 |
| CA2642650C true CA2642650C (en) | 2015-04-14 |
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| PL (1) | PL2004185T3 (enExample) |
| TW (1) | TWI394748B (enExample) |
| WO (1) | WO2007097992A2 (enExample) |
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| US7087576B2 (en) * | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| US20090203744A1 (en) * | 2005-07-29 | 2009-08-13 | Pande Y Surendrakumar Satyanarayan | Novel pyridine derivatives |
| JP2010520306A (ja) * | 2007-03-07 | 2010-06-10 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | エストロゲン関連受容体−αモジュレーターとしての置換フェノキシチアゾリジンジオン |
| WO2009025170A1 (ja) * | 2007-08-23 | 2009-02-26 | Konica Minolta Opto, Inc. | 長尺の位相差フィルム、長尺の楕円偏光フィルム、楕円偏光板、及び画像表示装置 |
| ATE536347T1 (de) | 2008-05-20 | 2011-12-15 | Merck Sharp & Dohme | Effiziente herstellung heterologer proteine unter verwendung von mannosyltransferaseinhibitoren |
| US20140187594A1 (en) * | 2010-07-28 | 2014-07-03 | Orchid Chemicals And Pharmaceuticals Ltd | Diphenyl ether compounds for the treatment of liver, lung disorders, diabetic complications and cardiovascular diseases |
| WO2012153775A1 (ja) | 2011-05-10 | 2012-11-15 | 国立大学法人神戸大学 | Ras機能阻害作用を有するチオキソチアゾリジン誘導体 |
| US12151372B2 (en) | 2019-02-27 | 2024-11-26 | Berkshire Grey Operating Company, Inc. | Systems and methods for hose routing in programmable motion systems |
| WO2020219480A1 (en) | 2019-04-25 | 2020-10-29 | Berkshire Grey, Inc. | Systems and methods for maintaining vacuum hose life in hose routing systems in programmable motion systems |
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| US5166137A (en) | 1991-03-27 | 1992-11-24 | Nobipols Forskningsstiftelse | Guluronic acid polymers and use of same for inhibition of cytokine production |
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| US5527546A (en) | 1994-08-10 | 1996-06-18 | Bayer Corporation | Human interleukin 6 inhibitor |
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| CA2289102A1 (en) * | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| EP1048659A4 (en) * | 1997-11-12 | 2002-11-20 | Inst Med Molecular Design Inc | Retinoid receptor Antagonist |
| US7105552B2 (en) * | 1998-05-08 | 2006-09-12 | Theracos, Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6331633B1 (en) | 1998-05-08 | 2001-12-18 | Calyx Therapeutics Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| EP1082323A2 (en) | 1998-06-05 | 2001-03-14 | AstraZeneca UK Limited | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| WO2000000194A1 (en) | 1998-06-27 | 2000-01-06 | Photogenesis, Inc. | Ophthalmic uses of ppargamma agonists and ppargamma antagonists |
| EP1108713A4 (en) | 1998-08-27 | 2006-04-05 | Ono Pharmaceutical Co | CARBOXYLENE DERIVATIVES AND MEDICAMENTS CONTAINING THEM AS AN ACTIVE COMPONENT |
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| HUP0200996A3 (en) | 1999-04-07 | 2003-01-28 | Sankyo Company Ltd Chuo Ku | Amine derivatives, pharmaceutical compositions containing them and their use |
| HRP20010795A2 (en) | 1999-04-28 | 2003-02-28 | Aventis Pharma Gmbh | Di-aryl acid derivatives as ppar receptor ligands |
| TWI284533B (en) | 1999-05-24 | 2007-08-01 | Sankyo Co | Pharmaceutical composition for treating hyperglycemia, impaired glucose tolerance, diabetes complications and for improving insulin resistant |
| ID29875A (id) | 1999-07-01 | 2001-10-18 | Geron Corp Cs | Penghambat-penghambat telomerase dan metode penggunaannya |
| JP2001072592A (ja) * | 1999-07-01 | 2001-03-21 | Kyowa Hakko Kogyo Co Ltd | テロメラーゼ阻害剤 |
| SE514748C2 (sv) * | 1999-08-03 | 2001-04-09 | Sahlin Gjutteknik Ab | Spolsten |
| US6730687B1 (en) | 1999-08-23 | 2004-05-04 | Kyorin Pharmaceutical Co., Ltd. | Substituted benzylthiazolidine-2, 4-dione derivatives |
| CN1384825A (zh) | 1999-08-31 | 2002-12-11 | 马克西亚药品公司 | 亚苄基－噻唑烷二酮及其类似物以及它们在治疗糖尿病中的应用 |
| JP2001199888A (ja) | 2000-01-24 | 2001-07-24 | Fujimoto Brothers:Kk | 糖尿病治療剤 |
| JP2001308814A (ja) | 2000-04-19 | 2001-11-02 | Hitachi Ltd | フレーム構成自動識別通信装置 |
| DE60115132T2 (de) | 2000-04-21 | 2006-07-06 | Pfizer Products Inc., Groton | Thyroid-Rezeptorliganden |
| US6620830B2 (en) | 2000-04-21 | 2003-09-16 | Pfizer, Inc. | Thyroid receptor ligands |
| US6680387B2 (en) | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| ATE363278T1 (de) | 2001-09-14 | 2007-06-15 | Novo Nordisk As | Neue liganden für die hisb10 zn2+ stellen des insulin-hexamers in der r-konformation |
| US7521465B2 (en) | 2003-01-17 | 2009-04-21 | Bexel Pharmaceuticals, Inc. | Diphenyl ether derivatives |
| US6794401B2 (en) | 2003-01-17 | 2004-09-21 | Bexel Pharmaceuticals, Inc. | Amino acid phenoxy ethers |
| JP2007523842A (ja) | 2003-03-11 | 2007-08-23 | ノボ ノルディスク アクティーゼルスカブ | 酸安定化されたインスリンを含有する薬学的製剤 |
| US7087576B2 (en) | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| JP2008533122A (ja) * | 2005-03-18 | 2008-08-21 | オーキッド ケミカルズ アンド ファーマシューティカルズ リミテッド | 新規なチロシン誘導体 |
-
2006
- 2006-02-21 US US11/359,657 patent/US7781464B2/en not_active Expired - Fee Related
-
2007
- 2007-02-15 ES ES07750819T patent/ES2427726T3/es active Active
- 2007-02-15 EP EP07750819.0A patent/EP2004185B1/en not_active Not-in-force
- 2007-02-15 WO PCT/US2007/004007 patent/WO2007097992A2/en not_active Ceased
- 2007-02-15 PL PL07750819T patent/PL2004185T3/pl unknown
- 2007-02-15 CA CA2642650A patent/CA2642650C/en not_active Expired - Fee Related
- 2007-02-15 JP JP2008556356A patent/JP5414280B2/ja not_active Expired - Fee Related
- 2007-02-26 TW TW096106502A patent/TWI394748B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP5414280B2 (ja) | 2014-02-12 |
| US7781464B2 (en) | 2010-08-24 |
| WO2007097992A2 (en) | 2007-08-30 |
| EP2004185A4 (en) | 2012-02-29 |
| WO2007097992A3 (en) | 2008-11-06 |
| CA2642650A1 (en) | 2007-08-30 |
| ES2427726T3 (es) | 2013-10-31 |
| EP2004185A2 (en) | 2008-12-24 |
| TW200812989A (en) | 2008-03-16 |
| EP2004185B1 (en) | 2013-06-26 |
| US20060247285A1 (en) | 2006-11-02 |
| PL2004185T3 (pl) | 2013-11-29 |
| TWI394748B (zh) | 2013-05-01 |
| JP2009528997A (ja) | 2009-08-13 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20200217 |