CA2536089A1 - Ppar modulators - Google Patents
Ppar modulators Download PDFInfo
- Publication number
- CA2536089A1 CA2536089A1 CA002536089A CA2536089A CA2536089A1 CA 2536089 A1 CA2536089 A1 CA 2536089A1 CA 002536089 A CA002536089 A CA 002536089A CA 2536089 A CA2536089 A CA 2536089A CA 2536089 A1 CA2536089 A1 CA 2536089A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- compound
- methyl
- hydrogen
- ethyl
- 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.)
- Abandoned
Links
- 101150014691 PPARA gene Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 322
- 150000003839 salts Chemical class 0.000 claims abstract description 102
- 239000012453 solvate Substances 0.000 claims abstract description 75
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims abstract description 51
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims abstract description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 34
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 16
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 16
- 208000008589 Obesity Diseases 0.000 claims abstract description 13
- 230000001404 mediated effect Effects 0.000 claims abstract description 13
- 235000020824 obesity Nutrition 0.000 claims abstract description 13
- 206010020772 Hypertension Diseases 0.000 claims abstract description 11
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 11
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 10
- -1 cyano, hydroxyl Chemical group 0.000 claims description 187
- 239000001257 hydrogen Substances 0.000 claims description 130
- 229910052739 hydrogen Inorganic materials 0.000 claims description 130
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 109
- 150000002431 hydrogen Chemical class 0.000 claims description 97
- 229910052760 oxygen Inorganic materials 0.000 claims description 86
- 125000003118 aryl group Chemical group 0.000 claims description 74
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 74
- 238000000034 method Methods 0.000 claims description 70
- 125000001072 heteroaryl group Chemical group 0.000 claims description 69
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 65
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 62
- 125000005843 halogen group Chemical group 0.000 claims description 62
- 229910052717 sulfur Inorganic materials 0.000 claims description 60
- 125000001188 haloalkyl group Chemical group 0.000 claims description 53
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 45
- 125000004104 aryloxy group Chemical group 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 39
- 102000004877 Insulin Human genes 0.000 claims description 37
- 108090001061 Insulin Proteins 0.000 claims description 37
- 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 description 37
- 229940125396 insulin Drugs 0.000 claims description 37
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 37
- 125000004043 oxo group Chemical group O=* 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 241000124008 Mammalia Species 0.000 claims description 33
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 33
- 201000010099 disease Diseases 0.000 claims description 33
- 238000011282 treatment Methods 0.000 claims description 33
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 27
- 239000008103 glucose Substances 0.000 claims description 27
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 26
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 206010022489 Insulin Resistance Diseases 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 206010012601 diabetes mellitus Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 102000005962 receptors Human genes 0.000 claims description 15
- 108020003175 receptors Proteins 0.000 claims description 15
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 12
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 10
- 229940123464 Thiazolidinedione Drugs 0.000 claims description 10
- 229940125753 fibrate Drugs 0.000 claims description 10
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 10
- 150000003536 tetrazoles Chemical class 0.000 claims description 10
- 150000001467 thiazolidinediones Chemical class 0.000 claims description 10
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 9
- 229940100389 Sulfonylurea Drugs 0.000 claims description 9
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 9
- 150000003857 carboxamides Chemical class 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229940124530 sulfonamide Drugs 0.000 claims description 9
- 150000003456 sulfonamides Chemical class 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 229940123208 Biguanide Drugs 0.000 claims description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- 150000004283 biguanides Chemical class 0.000 claims description 8
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 7
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 7
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 7
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 7
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 7
- 208000022531 anorexia Diseases 0.000 claims description 7
- 239000003529 anticholesteremic agent Substances 0.000 claims description 7
- 206010061428 decreased appetite Diseases 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 208000032841 Bulimia Diseases 0.000 claims description 6
- 239000004131 EU approved raising agent Substances 0.000 claims description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
- 230000003579 anti-obesity Effects 0.000 claims description 6
- 239000003524 antilipemic agent Substances 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 229950004994 meglitinide Drugs 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 229940088594 vitamin Drugs 0.000 claims description 6
- 235000013343 vitamin Nutrition 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 229930003231 vitamin Natural products 0.000 claims description 6
- 239000002404 acyltransferase inhibitor Substances 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005841 biaryl group Chemical group 0.000 claims 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 388
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 279
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 229
- 239000000203 mixture Substances 0.000 description 193
- 235000019439 ethyl acetate Nutrition 0.000 description 172
- 235000002639 sodium chloride Nutrition 0.000 description 138
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 136
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 131
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 118
- 235000019260 propionic acid Nutrition 0.000 description 105
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 101
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 99
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 98
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 35
- 239000002253 acid Substances 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
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- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 22
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- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/16—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C317/22—Sulfones; Sulfoxides having sulfone or sulfoxide groups and singly-bound oxygen atoms bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
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- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
- C07D277/22—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07C2601/00—Systems containing only non-condensed rings
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- C07C2601/00—Systems containing only non-condensed rings
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- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrrole Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
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Applications Claiming Priority (3)
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| US49654903P | 2003-08-20 | 2003-08-20 | |
| US60/496,549 | 2003-08-20 | ||
| PCT/US2004/024381 WO2005019151A1 (en) | 2003-08-20 | 2004-08-17 | Ppar modulators |
Publications (1)
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| CA2536089A1 true CA2536089A1 (en) | 2005-03-03 |
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| EP (1) | EP1660428A1 (https=) |
| JP (1) | JP2007502815A (https=) |
| CA (1) | CA2536089A1 (https=) |
| WO (1) | WO2005019151A1 (https=) |
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| CN101444496B (zh) | 2001-06-12 | 2011-04-13 | 维尔斯达医疗公司 | 用于治疗代谢失调的化合物 |
| CN1750758B (zh) | 2003-02-13 | 2012-06-20 | 维尔斯达医疗公司 | 用于治疗代谢紊乱的化合物 |
| WO2005042478A2 (en) * | 2003-09-19 | 2005-05-12 | Janssen Pharmaceutica, N.V. | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| DE602004028500D1 (de) * | 2003-09-19 | 2010-09-16 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyessigsäuren und analoga |
| US7622491B2 (en) * | 2004-08-13 | 2009-11-24 | Metabolex Inc. | Modulators of PPAR and methods of their preparation |
| MY147518A (en) * | 2004-09-15 | 2012-12-31 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| JPWO2006057448A1 (ja) * | 2004-11-26 | 2008-06-05 | 武田薬品工業株式会社 | アリールアルカン酸誘導体 |
| FR2882361A1 (fr) * | 2005-02-22 | 2006-08-25 | Aventis Pharma Sa | Nouveaux derives de 3-aryl-1,2-benzisoxazole, compositions les contenant et leur utilisation |
| EP1916234B1 (en) | 2005-07-29 | 2014-11-12 | Takeda Pharmaceutical Company Limited | Cyclopropanecarboxylic acid compound |
| US8097610B2 (en) | 2005-08-26 | 2012-01-17 | Shionogi & Co., Ltd. | Derivative having PPAR agonistic activity |
| JO3006B1 (ar) * | 2005-09-14 | 2016-09-05 | Janssen Pharmaceutica Nv | املاح ليسين مبتكرة من مشتقات حامض 4-((فينوكسي الكيل)ثيو) فينوكسي الخليك |
| UA95613C2 (ru) | 2005-11-09 | 2011-08-25 | Уеллстат Терепьютикс Корпорейшн | Соединения для лечения расстройсв метаболизма |
| PE20080188A1 (es) | 2006-04-18 | 2008-03-10 | Janssen Pharmaceutica Nv | Derivados del acido benzoazepin-oxi-acetico como agonistas de ppar-delta usados para aumentar hdl-c, reducir ldl-c y reducir colesterol |
| TW200838526A (en) | 2006-12-01 | 2008-10-01 | Astellas Pharma Inc | Carboxylic acid derivatives |
| FR2917084B1 (fr) * | 2007-06-05 | 2009-07-17 | Galderma Res & Dev | Nouveaux derives d'acide 3-phenyl propanoique activateurs des recpteurs de type ppar, leur methode de preparation et leur utilisation dans des compositions cosmetiques ou pharmaceutiques. |
| WO2011047315A1 (en) | 2009-10-15 | 2011-04-21 | Concert Pharmaceuticals, Inc. | Subsitituted benzimidazoles |
| RU2627703C2 (ru) * | 2010-07-23 | 2017-08-10 | Конекшис Лайф Сайенсиз Пвт. Лтд. | Агонисты gpr40 |
| CN103429581B (zh) | 2012-01-12 | 2015-08-26 | 江苏恒瑞医药股份有限公司 | 多环类衍生物、其制备方法及其在医药上的应用 |
| US9757529B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
| US9757395B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
| AU2013388034B2 (en) | 2013-04-30 | 2019-08-15 | Aspeya US Inc. | Dry powder formulations and methods of use |
| CN103524518B (zh) * | 2013-06-07 | 2017-05-10 | Tcl集团股份有限公司 | 轮状四烯类荧光化合物、制备方法和应用及电致发光器件 |
| JP6594351B2 (ja) | 2014-06-16 | 2019-10-23 | ジョンソン、マッセイ、パブリック、リミテッド、カンパニー | 新規中間体を含むアルキル化アリールピペラジン及びアルキル化アリールピペリジン化合物の製造方法 |
| JP7493449B2 (ja) | 2017-09-22 | 2024-05-31 | ヴェクチュラ インコーポレイテッド | ステアリン酸マグネシウムを含む乾燥粉末組成物 |
| US10786456B2 (en) | 2017-09-22 | 2020-09-29 | Otitopic Inc. | Inhaled aspirin and magnesium to treat inflammation |
| CN114901641B (zh) * | 2020-02-28 | 2025-06-17 | 四川科伦博泰生物医药股份有限公司 | 芳香族化合物及其药物组合物和用途 |
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| DK305884A (da) * | 1983-06-24 | 1984-12-25 | Yamanouchi Pharma Co Ltd | Phenoxyderivat, fremgangsmaade til fremstilling deraf og farmaceutisk praeparat indeholdende et saadant derivat |
| AU721452B2 (en) * | 1996-02-02 | 2000-07-06 | Merck & Co., Inc. | Antidiabetic agents |
| ATE451346T1 (de) * | 1998-03-10 | 2009-12-15 | Ono Pharmaceutical Co | Carbonsäurederivate und medikamente die diese als aktiven wirkstoff enthalten |
| CZ20033309A3 (cs) * | 2001-06-07 | 2004-05-12 | Eliálillyáandácompany | Modulátory receptorů aktivovaných peroxizomálními proliferátory }PPARB |
| HRP20031002A2 (en) * | 2001-06-07 | 2004-06-30 | Lilly Co Eli | Modulators of peroxisome proliferator activated receptors (ppar) |
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- 2004-08-17 EP EP04779442A patent/EP1660428A1/en not_active Withdrawn
- 2004-08-17 JP JP2006523861A patent/JP2007502815A/ja active Pending
- 2004-08-17 WO PCT/US2004/024381 patent/WO2005019151A1/en not_active Ceased
- 2004-08-17 US US10/566,291 patent/US20060257987A1/en not_active Abandoned
- 2004-08-17 CA CA002536089A patent/CA2536089A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
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| WO2005019151A1 (en) | 2005-03-03 |
| JP2007502815A (ja) | 2007-02-15 |
| EP1660428A1 (en) | 2006-05-31 |
| US20060257987A1 (en) | 2006-11-16 |
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| EEER | Examination request | ||
| FZDE | Discontinued |