HRP20030365A2 - Peroxisome proliferator activated receptor alpha agonists - Google Patents

Info

Publication number

HRP20030365A2

HRP20030365A2 HR20030365A HRP20030365A HRP20030365A2 HR P20030365 A2 HRP20030365 A2 HR P20030365A2 HR 20030365 A HR20030365 A HR 20030365A HR P20030365 A HRP20030365 A HR P20030365A HR P20030365 A2 HRP20030365 A2 HR P20030365A2

Authority

HR

Croatia

Prior art keywords

alkyl

group

compound

substituted

unsubstituted

Prior art date

2000-11-10

Links

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• 229940127520 Peroxisome Proliferator-activated Receptor alpha Agonists Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 290
• 238000002360 preparation method Methods 0.000 claims description 180
• 229910052739 hydrogen Inorganic materials 0.000 claims description 77
• 239000001257 hydrogen Substances 0.000 claims description 75
• 150000003839 salts Chemical class 0.000 claims description 63
• -1 nitro, phenyl Chemical group 0.000 claims description 56
• 238000000034 method Methods 0.000 claims description 55
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 50
• 229910052799 carbon Inorganic materials 0.000 claims description 49
• 150000002431 hydrogen Chemical group 0.000 claims description 47
• 229910052760 oxygen Inorganic materials 0.000 claims description 47
• 229920006395 saturated elastomer Polymers 0.000 claims description 46
• 229910052736 halogen Inorganic materials 0.000 claims description 43
• 150000002367 halogens Chemical class 0.000 claims description 43
• 229910052717 sulfur Inorganic materials 0.000 claims description 40
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 37
• 239000012453 solvate Substances 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 34
• 241000124008 Mammalia Species 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 31
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 229940124530 sulfonamide Drugs 0.000 claims description 26
• 150000003456 sulfonamides Chemical class 0.000 claims description 26
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 125000002947 alkylene group Chemical group 0.000 claims description 21
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 125000005466 alkylenyl group Chemical group 0.000 claims description 20
• 150000004677 hydrates Chemical class 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 18
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 17
• 239000002253 acid Substances 0.000 claims description 16
• 150000003536 tetrazoles Chemical class 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 150000003857 carboxamides Chemical class 0.000 claims description 13
• 125000000524 functional group Chemical group 0.000 claims description 13
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
• 208000011580 syndromic disease Diseases 0.000 claims description 13
• 150000001408 amides Chemical class 0.000 claims description 12
• 125000005001 aminoaryl group Chemical group 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• 125000001188 haloalkyl group Chemical group 0.000 claims description 12
• 125000005000 thioaryl group Chemical group 0.000 claims description 12
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 108010010234 HDL Lipoproteins Proteins 0.000 claims description 10
• 102000015779 HDL Lipoproteins Human genes 0.000 claims description 10
• 125000005002 aryl methyl group Chemical group 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 230000002265 prevention Effects 0.000 claims description 10
• 230000008569 process Effects 0.000 claims description 10
• 210000002966 serum Anatomy 0.000 claims description 10
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
• 208000008589 Obesity Diseases 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 9
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 9
• 235000020824 obesity Nutrition 0.000 claims description 9
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
• 235000019260 propionic acid Nutrition 0.000 claims description 9
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 8
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 108010007622 LDL Lipoproteins Proteins 0.000 claims description 7
• 102000007330 LDL Lipoproteins Human genes 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 6
• 150000003626 triacylglycerols Chemical class 0.000 claims description 6
• 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 230000005855 radiation Effects 0.000 claims description 5
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
• 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 description 4
• 229910052802 copper Inorganic materials 0.000 claims description 4
• 239000010949 copper Substances 0.000 claims description 4
• 239000008103 glucose Substances 0.000 claims description 4
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 4
• FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 4
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 3
• 230000002378 acidificating effect Effects 0.000 claims description 3
• 210000004369 blood Anatomy 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 230000002285 radioactive effect Effects 0.000 claims description 3
• 102000005962 receptors Human genes 0.000 claims description 3
• 108020003175 receptors Proteins 0.000 claims description 3
• 229910052722 tritium Inorganic materials 0.000 claims description 3
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
• 125000004432 carbon atom Chemical group C* 0.000 claims 10
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
• 125000004171 alkoxy aryl group Chemical group 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 125000003107 substituted aryl group Chemical group 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 653
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 245
• 239000000243 solution Substances 0.000 description 241
• 235000019439 ethyl acetate Nutrition 0.000 description 219
• 229940093499 ethyl acetate Drugs 0.000 description 208
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 207
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 198
• 239000000203 mixture Substances 0.000 description 181
• 239000011541 reaction mixture Substances 0.000 description 147
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 113
• 229910001868 water Inorganic materials 0.000 description 109
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 107
• 229910052938 sodium sulfate Inorganic materials 0.000 description 107
• 235000011152 sodium sulphate Nutrition 0.000 description 107
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
• 239000007832 Na2SO4 Substances 0.000 description 88
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• 239000012044 organic layer Substances 0.000 description 85
• 238000004949 mass spectrometry Methods 0.000 description 83
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 83
• 239000002904 solvent Substances 0.000 description 83
• 239000000047 product Substances 0.000 description 82
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 79
• 239000003921 oil Substances 0.000 description 79
• 235000019198 oils Nutrition 0.000 description 79
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 74
• 239000007787 solid Substances 0.000 description 73
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
• 238000000746 purification Methods 0.000 description 66
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
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• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 57
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• 238000003818 flash chromatography Methods 0.000 description 52
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 48
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• 229910000027 potassium carbonate Inorganic materials 0.000 description 41
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• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 32
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• 150000004702 methyl esters Chemical class 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
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• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
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• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
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