MX2008001929A - Derivados de xantina como agonistas de hm74a selectivos. - Google Patents
Derivados de xantina como agonistas de hm74a selectivos.Info
- Publication number
- MX2008001929A MX2008001929A MX2008001929A MX2008001929A MX2008001929A MX 2008001929 A MX2008001929 A MX 2008001929A MX 2008001929 A MX2008001929 A MX 2008001929A MX 2008001929 A MX2008001929 A MX 2008001929A MX 2008001929 A MX2008001929 A MX 2008001929A
- Authority
- MX
- Mexico
- Prior art keywords
- mmol
- chloro
- mixture
- dihydro
- purine
- 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 20
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title abstract description 8
- 239000000556 agonist Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 332
- 238000000034 method Methods 0.000 claims abstract description 152
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 claims abstract description 29
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 102000005962 receptors Human genes 0.000 claims abstract description 14
- 108020003175 receptors Proteins 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 230000004913 activation Effects 0.000 claims abstract description 9
- 230000009286 beneficial effect Effects 0.000 claims abstract description 9
- -1 N7-protected xanthine Chemical class 0.000 claims description 291
- 125000003118 aryl group Chemical group 0.000 claims description 42
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 25
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 229960003512 nicotinic acid Drugs 0.000 claims description 21
- 235000001968 nicotinic acid Nutrition 0.000 claims description 21
- 239000011664 nicotinic acid Substances 0.000 claims description 21
- 150000005829 chemical entities Chemical class 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 230000029936 alkylation Effects 0.000 claims description 15
- 238000005804 alkylation reaction Methods 0.000 claims description 15
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 15
- 201000001320 Atherosclerosis Diseases 0.000 claims description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 10
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 9
- 206010019280 Heart failures Diseases 0.000 claims description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 9
- 238000010511 deprotection reaction Methods 0.000 claims description 9
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 239000003981 vehicle Substances 0.000 claims description 9
- 206010002383 Angina Pectoris Diseases 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 208000006011 Stroke 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
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 8
- 208000029078 coronary artery disease Diseases 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 230000026030 halogenation Effects 0.000 claims description 5
- 238000005658 halogenation reaction Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229940075420 xanthine Drugs 0.000 claims description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 4
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 4
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229940125753 fibrate Drugs 0.000 claims description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 23
- 201000010099 disease Diseases 0.000 abstract description 22
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 431
- 239000000203 mixture Substances 0.000 description 373
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 364
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 219
- 235000019439 ethyl acetate Nutrition 0.000 description 173
- 239000007787 solid Substances 0.000 description 163
- 239000000243 solution Substances 0.000 description 157
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 144
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 138
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 136
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 135
- 239000000047 product Substances 0.000 description 131
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 125
- 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 120
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 114
- 229910052757 nitrogen Inorganic materials 0.000 description 109
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 106
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 98
- 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 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 75
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 71
- 239000012044 organic layer Substances 0.000 description 70
- 239000012267 brine Substances 0.000 description 69
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 69
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 65
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 63
- 238000003756 stirring Methods 0.000 description 59
- 239000012074 organic phase Substances 0.000 description 55
- 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 54
- 238000000746 purification Methods 0.000 description 50
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 46
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 45
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 38
- 239000012043 crude product Substances 0.000 description 37
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 36
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 36
- 239000000377 silicon dioxide Substances 0.000 description 35
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
- 235000019341 magnesium sulphate Nutrition 0.000 description 34
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 30
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 29
- 229910000024 caesium carbonate Inorganic materials 0.000 description 27
- 239000000463 material Substances 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000001816 cooling Methods 0.000 description 23
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 22
- 238000009472 formulation Methods 0.000 description 20
- 239000010410 layer Substances 0.000 description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 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 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 150000003839 salts Chemical class 0.000 description 18
- 229910000029 sodium carbonate Inorganic materials 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 238000012360 testing method Methods 0.000 description 15
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 15
- 238000005406 washing Methods 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 239000012535 impurity Substances 0.000 description 14
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 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
- 239000008346 aqueous phase Substances 0.000 description 12
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000000634 powder X-ray diffraction Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 11
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- FAIAJSOSTNJZCI-UHFFFAOYSA-N purine-2,6-dione Chemical compound O=C1NC(=O)C2=NC=NC2=N1 FAIAJSOSTNJZCI-UHFFFAOYSA-N 0.000 description 10
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 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 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 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 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 125000002950 monocyclic group Chemical group 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
- 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 7
- 101001035752 Homo sapiens Hydroxycarboxylic acid receptor 3 Proteins 0.000 description 7
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- 235000021588 free fatty acids Nutrition 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 150000005830 nonesterified fatty acids Chemical class 0.000 description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 102100039356 Hydroxycarboxylic acid receptor 3 Human genes 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000006071 cream Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- ZXSNABHDRKDSMU-UHFFFAOYSA-N ethyl 4-(3-butyl-8-chloro-2,6-dioxo-7h-purin-1-yl)butanoate Chemical compound O=C1N(CCCC(=O)OCC)C(=O)N(CCCC)C2=C1NC(Cl)=N2 ZXSNABHDRKDSMU-UHFFFAOYSA-N 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 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
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- MYZJTONHQMUXGQ-UHFFFAOYSA-N ethyl 5-(8-chloro-2,6-dioxo-3-pentyl-7h-purin-1-yl)pentanoate Chemical compound O=C1N(CCCCC(=O)OCC)C(=O)N(CCCCC)C2=C1NC(Cl)=N2 MYZJTONHQMUXGQ-UHFFFAOYSA-N 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
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- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
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- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 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
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
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Classifications
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- 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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- 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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- A—HUMAN NECESSITIES
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- 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
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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
- 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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- Veterinary Medicine (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Nutrition Science (AREA)
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- 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)
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| 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/EP2006/007869 WO2007017262A1 (en) | 2005-08-10 | 2006-08-08 | Xanthine derivatives as selective hm74a agonists |
Publications (1)
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| MX2008001929A MX2008001929A (es) | 2005-08-10 | 2006-08-08 | Derivados de xantina como agonistas de hm74a selectivos. |
| MX2008001931A MX2008001931A (es) | 2005-08-10 | 2006-08-08 | Derivados de xantina como agonistas selectivos de hm74a. |
Family Applications After (1)
| 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. |
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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 |
| CA2556073C (en) * | 2004-02-14 | 2012-01-10 | Smithkline Beecham Corporation | 8-chloro-1,3-disubstituted xanthine derivatives as hm74a receptor modulators |
| DE102004030502A1 (de) | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
| US8143264B2 (en) * | 2005-08-10 | 2012-03-27 | Glaxosmithkline Llc | Xanthine derivatives as selective HM74A agonists |
| US7511050B2 (en) | 2006-06-23 | 2009-03-31 | Incyte Corporation | Purinone derivatives as HM74A agonists |
| AR061626A1 (es) | 2006-06-23 | 2008-09-10 | Incyte Corp | Derivados de purinona como agonistas de hm74a |
| JP2010500300A (ja) | 2006-08-08 | 2010-01-07 | サノフィ−アベンティス | アリールアミノアリール−アルキル−置換イミダゾリジン−２，４−ジオン、それらの製造法、それらの化合物を含有する薬剤、およびそれらの使用 |
| 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 |
| WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | 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 |
| DK2370440T3 (en) | 2008-12-08 | 2014-12-08 | Glaxosmithkline Llc | 8-Chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dion2-amino-2- (hydroxymethyl) -1,3-propandiolanhydrat for the treatment of diseases |
| SG178880A1 (en) | 2009-08-26 | 2012-04-27 | Sanofi Sa | Novel crystalline heteroaromatic fluoroglycoside hydrates, pharmaceuticals comprising these compounds and their use |
| 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 |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| 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 |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| PH12013500301A1 (en) * | 2010-08-16 | 2013-03-25 | Boehringer Ingelheim Int | Oxadiazole inhibitors of leukotriene production |
| EP2619196B1 (en) * | 2010-09-23 | 2015-09-16 | Boehringer Ingelheim International GmbH | Oxadiazole inhibitors of leukotriene production |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| 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 |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| WO2012120055A1 (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 |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013178572A1 (en) * | 2012-05-30 | 2013-12-05 | F. Hoffmann-La Roche Ag | Triazolo compounds as pde10 inhibitors |
| MX370372B (es) * | 2013-03-15 | 2019-12-11 | Hydra Biosciences Inc | Xantinas sustituidas y metodos de uso de las mismas. |
| EA201591962A1 (ru) | 2013-05-10 | 2016-06-30 | Нимбус Аполло, Инк. | Ингибиторы акк и их применение |
| EP2994128B1 (en) | 2013-05-10 | 2019-01-30 | Gilead Apollo, LLC | Acc inhibitors and uses thereof |
| AU2014262638A1 (en) | 2013-05-10 | 2015-11-26 | Gilead Apollo, Llc | ACC inhibitors and uses thereof |
| AU2014262636A1 (en) | 2013-05-10 | 2015-11-26 | Gilead Apollo, Llc | ACC inhibitors and uses thereof |
| CN105646492B (zh) * | 2014-11-14 | 2019-04-09 | 中国医学科学院药物研究所 | 含五元芳杂环的取代黄嘌呤类化合物及其制备方法和用途 |
| DE102017000359A1 (de) | 2016-08-26 | 2018-03-01 | Bihl+Wiedemann Gmbh | Diagnose-Repeater für AS-Interface Netze |
| JP7178357B2 (ja) * | 2017-03-07 | 2022-11-25 | エフ．ホフマン－ラ ロシュ アーゲー | オキサジアゾール一過性受容器電位チャネル阻害剤 |
| BR112021002207A2 (pt) | 2018-08-10 | 2021-05-04 | Diapin Therapeutics, Llc | tri-peptídeos e tratamento de distúrbios metabólicos, cardiovasculares e inflamatórios |
| CN112724141A (zh) * | 2021-01-21 | 2021-04-30 | 南京艾美斐生物医药科技有限公司 | 一种gpr109a蛋白受体抑制剂及其制备和应用 |
| US20250136587A1 (en) * | 2022-02-03 | 2025-05-01 | D. E. Shaw Research, Llc | N3-substituted uracil compounds as trpa1 inhibitors |
| JP2026503850A (ja) * | 2023-01-30 | 2026-01-30 | ディー．イー．ショウ リサーチ，エルエルシー | Ｔｒｐａ１阻害剤としての二環式イミド化合物 |
| AR133217A1 (es) * | 2023-07-10 | 2025-09-10 | De Shaw Res Llc | Inhibidores de trpa1 bicíclicos y monocíclicos |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2797220A (en) | 1954-12-02 | 1957-06-25 | Univ Michigan | Substituted paraxanthines |
| GB8906792D0 (en) | 1989-03-23 | 1989-05-10 | Beecham Wuelfing Gmbh & Co Kg | Treatment and compounds |
| NZ240644A (en) | 1990-11-21 | 1994-08-26 | Smithkline Beecham Corp | Use of xanthine derivatives to inhibit the production of tumour necrosis factor (tnf) |
| WO1993016699A1 (en) | 1992-02-21 | 1993-09-02 | Smithkline Beecham Corporation | Tnf inhibitors |
| CA2112239C (en) | 1992-03-04 | 2000-05-09 | James A. Bianco | Enantiomeric hydroxylated xanthine compounds |
| US6693105B1 (en) | 1992-11-16 | 2004-02-17 | Cell Therapeutics, Inc. | Hydroxyl-containing compounds |
| US5473070A (en) | 1992-11-16 | 1995-12-05 | Cell Therapeutics, Inc. | Substituted long chain alcohol xanthine compounds |
| US6469017B1 (en) | 1998-01-16 | 2002-10-22 | Cell Therapeutics, Inc. | Method of inhibiting interleukin-12 signaling |
| US5780476A (en) | 1992-11-16 | 1998-07-14 | Cell Therapeutics, Inc. | Hydroxyl-containing xanthine compounds |
| IL109161A0 (en) | 1993-03-31 | 1994-06-24 | Cell Therapeutics Inc | Amino alcohol derivatives, methods for the preparation thereof, and pharmaceutical compositions containing the same |
| US5670506A (en) | 1993-04-05 | 1997-09-23 | Cell Therapeutics, Inc. | Halogen, isothiocyanate or azide substituted xanthines |
| AU6702894A (en) | 1993-04-09 | 1994-11-08 | Cell Therapeutics, Inc. | Ring-substituted cell signaling inhibitors |
| WO1995020589A1 (en) | 1994-01-28 | 1995-08-03 | Cell Therapeutics, Inc. | Cell signaling inhibitors |
| JPH09511496A (ja) | 1994-02-18 | 1997-11-18 | セル・セラピューティックス・インコーポレーテッド | 細胞内メッセンジャー |
| US6780865B1 (en) | 1994-02-18 | 2004-08-24 | Cell Therapeutics, Inc. | Compounds having selective hydrolytic potentials |
| US6103730A (en) | 1994-03-24 | 2000-08-15 | Cell Therapeutics, Inc. | Amine substituted compounds |
| US6878715B1 (en) | 1994-02-18 | 2005-04-12 | Cell Therapeutics, Inc. | Therapeutic compounds for inhibiting interleukin-12 signals and method for using same |
| US5807861A (en) | 1994-03-24 | 1998-09-15 | Cell Therapeutics, Inc. | Amine substituted xanthinyl compounds |
| US6323201B1 (en) * | 1994-12-29 | 2001-11-27 | The Regents Of The University Of California | Compounds for inhibition of ceramide-mediated signal transduction |
| WO2000061583A1 (en) | 1995-06-07 | 2000-10-19 | Cell Therapeutics, Inc. | Xanthine derivatives and analogs as cell signaling inhibitors |
| AR015966A1 (es) | 1997-10-17 | 2001-05-30 | Smithkline Beecham Corp | Uso de un compuesto inhibidor de pde4 para la preparacion de un medicamento util para el tratamiento de prurito |
| US20030207901A1 (en) | 1999-07-27 | 2003-11-06 | Cell Therapeutics, Inc. | Hydroxyl-containing compounds |
| US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
| US6586429B2 (en) * | 2000-11-29 | 2003-07-01 | Cell Therapeutics, Inc. | Tricyclic fused xanthine compounds and their uses |
| SI1953162T1 (sl) | 2001-02-24 | 2012-09-28 | Boehringer Ingelheim Pharma | Ksantinski derivati, njihova priprava in njihova uporaba kot zdravila |
| EP1377834A2 (en) | 2001-04-11 | 2004-01-07 | Glaxo Group Limited | Medicaments which are modulators of hm74 and/or hm74a activity |
| EP1404675B1 (en) * | 2001-07-03 | 2008-03-12 | Novo Nordisk A/S | Dpp-iv-inhibiting purine derivatives for the treatment of diabetes |
| DE60304911D1 (de) | 2002-02-25 | 2006-06-08 | Eisai Co Ltd | Xanthin-Derivate als DPP-IV-Inhibitoren |
| US7482337B2 (en) | 2002-11-08 | 2009-01-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions |
| CN1227492C (zh) * | 2003-03-11 | 2005-11-16 | 张跃 | 一种吸收式空调主体 |
| GB0319124D0 (en) * | 2003-08-14 | 2003-09-17 | Smithkline Beecham Corp | Chemical compounds |
| CA2556073C (en) * | 2004-02-14 | 2012-01-10 | Smithkline Beecham Corporation | 8-chloro-1,3-disubstituted xanthine derivatives as hm74a receptor modulators |
| WO2006045564A1 (en) * | 2004-10-22 | 2006-05-04 | Smithkline Beecham Corporation | Xanthine derivatives with hm74a receptor activity |
| WO2006045565A1 (en) * | 2004-10-22 | 2006-05-04 | Smithkline Beecham Corporation | Xanthine derivatives with hm74a receptor activity |
| US20090209561A1 (en) * | 2004-10-22 | 2009-08-20 | Richard Jonathan Daniel Hatley | Xanthine Derivatives with HM74A Receptor Activity |
| EP1848699A1 (en) | 2005-02-14 | 2007-10-31 | Smithkline Beecham Corporation | Anthranilic acid derivatives as hm74a receptor agonists |
| US8143264B2 (en) * | 2005-08-10 | 2012-03-27 | Glaxosmithkline Llc | Xanthine derivatives as selective HM74A agonists |
| GB0516462D0 (en) * | 2005-08-10 | 2005-09-14 | Smithkline Beecham Corp | Novel compounds |
| DE102008009758A1 (de) * | 2008-02-18 | 2009-08-20 | Beiersdorf Ag | Verwendung von 3-(4-Hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-propan-1-on zur verbesserten Hautkonturierung bzw. gegen Cellulite |
| DK2370440T3 (en) | 2008-12-08 | 2014-12-08 | Glaxosmithkline Llc | 8-Chloro-3-pentyl-3,7-dihydro-1H-purine-2,6-dion2-amino-2- (hydroxymethyl) -1,3-propandiolanhydrat for the treatment of diseases |
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