MX2008001931A - Derivados de xantina como agonistas selectivos de hm74a. - Google Patents
Derivados de xantina como agonistas selectivos de hm74a.Info
- Publication number
- MX2008001931A MX2008001931A MX2008001931A MX2008001931A MX2008001931A MX 2008001931 A MX2008001931 A MX 2008001931A MX 2008001931 A MX2008001931 A MX 2008001931A MX 2008001931 A MX2008001931 A MX 2008001931A MX 2008001931 A MX2008001931 A MX 2008001931A
- Authority
- MX
- Mexico
- Prior art keywords
- mmol
- chloro
- butyl
- mixture
- dihydro
- Prior art date
Links
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title abstract description 8
- 239000000556 agonist Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 282
- 238000000034 method Methods 0.000 claims abstract description 116
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 claims abstract description 27
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 230000004913 activation Effects 0.000 claims abstract description 10
- 230000009286 beneficial effect Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims description 43
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 37
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 33
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 24
- 150000005829 chemical entities Chemical class 0.000 claims description 21
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229960003512 nicotinic acid Drugs 0.000 claims description 19
- 235000001968 nicotinic acid Nutrition 0.000 claims description 19
- 239000011664 nicotinic acid Substances 0.000 claims description 19
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 14
- 201000001320 Atherosclerosis Diseases 0.000 claims description 13
- 230000029936 alkylation Effects 0.000 claims description 13
- 238000005804 alkylation reaction Methods 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 230000007812 deficiency Effects 0.000 claims description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 10
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 9
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 9
- 230000000747 cardiac effect Effects 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 206010002383 Angina Pectoris Diseases 0.000 claims description 8
- 208000007536 Thrombosis Diseases 0.000 claims description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- 208000020832 chronic kidney disease Diseases 0.000 claims description 8
- 208000029078 coronary artery disease Diseases 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 206010022489 Insulin Resistance Diseases 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 229940075420 xanthine Drugs 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
- 230000004968 inflammatory condition Effects 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 150000003536 tetrazoles Chemical group 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 3
- 229940125753 fibrate Drugs 0.000 claims description 3
- 230000026030 halogenation Effects 0.000 claims description 3
- 238000005658 halogenation reaction Methods 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 208000035762 Disorder of lipid metabolism Diseases 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 26
- 102000005962 receptors Human genes 0.000 abstract description 14
- 108020003175 receptors Proteins 0.000 abstract description 14
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 309
- 239000000203 mixture Substances 0.000 description 268
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 261
- -1 - (CH2) Chemical group 0.000 description 171
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 139
- 239000000243 solution Substances 0.000 description 136
- 235000019439 ethyl acetate Nutrition 0.000 description 122
- 239000007787 solid Substances 0.000 description 117
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 115
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 105
- 239000000047 product Substances 0.000 description 99
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 85
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 72
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 70
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 68
- 229910052757 nitrogen Inorganic materials 0.000 description 68
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
- 239000012044 organic layer Substances 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- 239000012267 brine Substances 0.000 description 43
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
- 238000000746 purification Methods 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 35
- 238000003756 stirring Methods 0.000 description 35
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000000377 silicon dioxide Substances 0.000 description 30
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 29
- 239000012043 crude product Substances 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000001819 mass spectrum Methods 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 23
- 238000009472 formulation Methods 0.000 description 20
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 150000003839 salts Chemical class 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 17
- 238000001816 cooling Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- 229910000024 caesium carbonate Inorganic materials 0.000 description 14
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
- 239000012535 impurity Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- UEHBSOZKEHODBZ-UHFFFAOYSA-N 3-butyl-8-chloro-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC)C2=C1N(CC=C)C(Cl)=N2 UEHBSOZKEHODBZ-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000010828 elution Methods 0.000 description 12
- 238000000634 powder X-ray diffraction Methods 0.000 description 12
- YVDUEJFLTVCEMN-UHFFFAOYSA-N O=C(C1=C(N2)N=CN1)N(CCCCC1=COC(C3=NC=CC=C3)=N1)C2=O Chemical compound O=C(C1=C(N2)N=CN1)N(CCCCC1=COC(C3=NC=CC=C3)=N1)C2=O YVDUEJFLTVCEMN-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 10
- BAXZLWYKDFEHAS-UHFFFAOYSA-N 5-(3-butyl-8-chloro-2,6-dioxo-7h-purin-1-yl)-n'-hydroxypentanimidamide Chemical compound O=C1N(CCCCC(=N)NO)C(=O)N(CCCC)C2=C1NC(Cl)=N2 BAXZLWYKDFEHAS-UHFFFAOYSA-N 0.000 description 9
- WTUVPERXQXSPFE-UHFFFAOYSA-N 8-chloro-3-pentyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCC)C2=C1N(CC=C)C(Cl)=N2 WTUVPERXQXSPFE-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
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- 235000017550 sodium carbonate Nutrition 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
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- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 7
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 7
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- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
- MSRIEVNGZFTWKY-UHFFFAOYSA-N 4-(3-butyl-8-chloro-2,6-dioxo-7h-purin-1-yl)-n'-hydroxybutanimidamide Chemical compound O=C1N(CCCC(=N)NO)C(=O)N(CCCC)C2=C1NC(Cl)=N2 MSRIEVNGZFTWKY-UHFFFAOYSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
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- IRJKSAIGIYODAN-ISLYRVAYSA-N benzyl (ne)-n-phenylmethoxycarbonyliminocarbamate Chemical compound C=1C=CC=CC=1COC(=O)/N=N/C(=O)OCC1=CC=CC=C1 IRJKSAIGIYODAN-ISLYRVAYSA-N 0.000 description 5
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- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 5
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- 239000012528 membrane Substances 0.000 description 5
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 4
- KMQOTDNPNJWPLD-UHFFFAOYSA-N 3-(4-benzyl-1,3-oxazol-2-yl)propan-1-ol Chemical compound OCCCc1nc(Cc2ccccc2)co1 KMQOTDNPNJWPLD-UHFFFAOYSA-N 0.000 description 4
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 4
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LWASFOOUZTWLGH-UHFFFAOYSA-N tert-butyl n-[[2-(2-chloro-4-fluorophenyl)acetyl]amino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)CC1=CC=C(F)C=C1Cl LWASFOOUZTWLGH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P3/06—Antihyperlipidemics
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- 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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- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0516464A GB0516464D0 (en) | 2005-08-10 | 2005-08-10 | Novel compounds |
| GB0607736A GB0607736D0 (en) | 2006-04-19 | 2006-04-19 | Novel compounds |
| GB0614569A GB0614569D0 (en) | 2006-07-21 | 2006-07-21 | Novel compounds |
| PCT/EP2006/007865 WO2007017261A1 (en) | 2005-08-10 | 2006-08-08 | Xanthine derivatives as selective hm74a agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2008001931A true MX2008001931A (es) | 2008-03-24 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| MX2008001931A MX2008001931A (es) | 2005-08-10 | 2006-08-08 | Derivados de xantina como agonistas selectivos de hm74a. |
| MX2008001929A MX2008001929A (es) | 2005-08-10 | 2006-08-08 | Derivados de xantina como agonistas de hm74a selectivos. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2008001929A MX2008001929A (es) | 2005-08-10 | 2006-08-08 | Derivados de xantina como agonistas de hm74a selectivos. |
Country Status (28)
| Country | Link |
|---|---|
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| EP (3) | EP1912992A1 (enExample) |
| JP (2) | JP2009504592A (enExample) |
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| AT (1) | ATE487719T1 (enExample) |
| AU (2) | AU2006278215A1 (enExample) |
| BR (2) | BRPI0615145A2 (enExample) |
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| CR (2) | CR9748A (enExample) |
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| IL (2) | IL189083A0 (enExample) |
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| MX (2) | MX2008001931A (enExample) |
| MY (1) | MY142067A (enExample) |
| NO (2) | NO20081212L (enExample) |
| NZ (1) | NZ565494A (enExample) |
| PE (1) | PE20070405A1 (enExample) |
| PL (1) | PL1912991T3 (enExample) |
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| US7495005B2 (en) * | 2002-08-22 | 2009-02-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, their preparation and their use in pharmaceutical compositions |
| SI1781657T1 (sl) * | 2004-02-14 | 2013-07-31 | Glaxosmithkline Intellectual Property Development Limited | Zdravila z aktivnostjo na receptor hm74a |
| DE102004030502A1 (de) | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
| EP1912992A1 (en) * | 2005-08-10 | 2008-04-23 | SmithKline Beecham Corporation | Xanthine derivatives as selective hm74a agonists |
| CA2656039A1 (en) | 2006-06-23 | 2007-12-27 | Incyte Corporation | Purinone derivatives as hm74a agonists |
| AR061626A1 (es) | 2006-06-23 | 2008-09-10 | Incyte Corp | Derivados de purinona como agonistas de hm74a |
| AU2007283113A1 (en) | 2006-08-08 | 2008-02-14 | Sanofi-Aventis | Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, processes for preparing them, medicaments comprising these compounds, and their use |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE102007054497B3 (de) | 2007-11-13 | 2009-07-23 | Sanofi-Aventis Deutschland Gmbh | Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung |
| US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
| WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
| PL2370440T3 (pl) | 2008-12-08 | 2015-05-29 | Glaxosmithkline Llc | Bezwodnik 2-amino-2-(hydroksymetylo)-1,3-propanodiolu 8-chloru-3-pentylo-3,7-dihydro-1H-puryno-2,6-dionu do leczenia chorób |
| JP2013503135A (ja) | 2009-08-26 | 2013-01-31 | サノフイ | 新規な結晶性複素芳香族フルオログリコシド水和物、その化合物を含んでなる医薬及びその使用 |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| KR101799429B1 (ko) | 2010-05-03 | 2017-11-21 | 에스케이바이오팜 주식회사 | 신경 세포 사멸 또는 신경 퇴화를 억제하기 위한 약학적 조성물 |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| PH12013500301A1 (en) * | 2010-08-16 | 2013-03-25 | Boehringer Ingelheim Int | Oxadiazole inhibitors of leukotriene production |
| US8580825B2 (en) * | 2010-09-23 | 2013-11-12 | Boehringer Ingelheim International Gmbh | Oxadiazole inhibitors of leukotriene production |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
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