IL177051A - Xanthine derivatives, pharmaceutical formulations comprising same, method for their preparation and use thereof in the preparation of medicaments - Google Patents
Xanthine derivatives, pharmaceutical formulations comprising same, method for their preparation and use thereof in the preparation of medicamentsInfo
- Publication number
- IL177051A IL177051A IL177051A IL17705106A IL177051A IL 177051 A IL177051 A IL 177051A IL 177051 A IL177051 A IL 177051A IL 17705106 A IL17705106 A IL 17705106A IL 177051 A IL177051 A IL 177051A
- Authority
- IL
- Israel
- Prior art keywords
- purine
- chloro
- dione
- dihydro
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 48
- 239000003814 drug Substances 0.000 title claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 14
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims description 13
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 171
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 30
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 23
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 20
- 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
- 239000012453 solvate Substances 0.000 claims description 14
- 230000029936 alkylation Effects 0.000 claims description 12
- 238000005804 alkylation reaction Methods 0.000 claims description 12
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims description 11
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 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
- 239000000969 carrier Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 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
- IRKQPAMTLHYJDE-UHFFFAOYSA-N 8-chloro-1-methyl-3-pentyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1NC(Cl)=N2 IRKQPAMTLHYJDE-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229940075420 xanthine Drugs 0.000 claims description 3
- CGAMDQCXAAOFSR-UHFFFAOYSA-N 8-chloro-3-pentyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCC)C2=C1NC(Cl)=N2 CGAMDQCXAAOFSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 157
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 155
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 100
- 239000000203 mixture Substances 0.000 description 99
- 239000000243 solution Substances 0.000 description 85
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 82
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 65
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
- 239000007787 solid Substances 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 229910052757 nitrogen Inorganic materials 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 44
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 44
- 239000000047 product Substances 0.000 description 41
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 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 35
- 238000003756 stirring Methods 0.000 description 35
- -1 alkali metal salts Chemical class 0.000 description 33
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 33
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 33
- 239000012267 brine Substances 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 125000000217 alkyl group Chemical group 0.000 description 31
- 230000008569 process Effects 0.000 description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 229940093499 ethyl acetate Drugs 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 102000005962 receptors Human genes 0.000 description 21
- 108020003175 receptors Proteins 0.000 description 21
- 229910000029 sodium carbonate Inorganic materials 0.000 description 21
- 201000010099 disease Diseases 0.000 description 19
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 18
- 239000000284 extract Substances 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 125000003342 alkenyl group Chemical group 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 238000000746 purification Methods 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 229910052731 fluorine Inorganic materials 0.000 description 13
- 201000001320 Atherosclerosis Diseases 0.000 description 12
- 239000011737 fluorine Substances 0.000 description 12
- 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 12
- KOZZYIHVPUEIPB-UHFFFAOYSA-N 8-chloro-7-prop-2-enyl-3h-purine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(Cl)N2CC=C KOZZYIHVPUEIPB-UHFFFAOYSA-N 0.000 description 11
- 208000024172 Cardiovascular disease Diseases 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 206010003210 Arteriosclerosis Diseases 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 208000011775 arteriosclerosis disease Diseases 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000037356 lipid metabolism Effects 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 208000000103 Anorexia Nervosa Diseases 0.000 description 9
- 206010019280 Heart failures Diseases 0.000 description 9
- 206010022489 Insulin Resistance Diseases 0.000 description 9
- 208000008589 Obesity Diseases 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 235000020824 obesity Nutrition 0.000 description 9
- 206010002383 Angina Pectoris Diseases 0.000 description 8
- 208000007536 Thrombosis Diseases 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 8
- 208000029078 coronary artery disease Diseases 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
- 101001035752 Homo sapiens Hydroxycarboxylic acid receptor 3 Proteins 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 102100039356 Hydroxycarboxylic acid receptor 3 Human genes 0.000 description 6
- 208000018262 Peripheral vascular disease Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- 208000020832 chronic kidney disease Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- CSIFGMFVGDBOQC-UHFFFAOYSA-N 3-iminobutanenitrile Chemical compound CC(=N)CC#N CSIFGMFVGDBOQC-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 4
- 240000007472 Leucaena leucocephala Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 3
- OZPCWWUKRLUQSS-UHFFFAOYSA-N 8-Chloroxanthine Chemical compound N1C(=O)NC(=O)C2=C1N=C(Cl)N2 OZPCWWUKRLUQSS-UHFFFAOYSA-N 0.000 description 3
- MBGFDVLXWNQMKD-UHFFFAOYSA-N 8-chloro-1-methyl-7-prop-2-enyl-3h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)NC2=C1N(CC=C)C(Cl)=N2 MBGFDVLXWNQMKD-UHFFFAOYSA-N 0.000 description 3
- QQXWQTCMAPWGJA-UHFFFAOYSA-N 8-chloro-3-(2-cyclopropylethyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC(Cl)=NC=2N1CCC1CC1 QQXWQTCMAPWGJA-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 108091006027 G proteins Proteins 0.000 description 3
- 102000030782 GTP binding Human genes 0.000 description 3
- 108091000058 GTP-Binding Proteins 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 230000006020 chronic inflammation Effects 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000026030 halogenation Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 3
- 239000007758 minimum essential medium Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- BHBVWEDFVDRWAZ-UHFFFAOYSA-N 1,3-dibutyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC=C)C=N2 BHBVWEDFVDRWAZ-UHFFFAOYSA-N 0.000 description 2
- HDAPVDGMACVEKL-UHFFFAOYSA-N 1,3-dibutyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC=N2 HDAPVDGMACVEKL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BIAAQBNMRITRDV-UHFFFAOYSA-N 1-(chloromethoxy)-2-methoxyethane Chemical compound COCCOCCl BIAAQBNMRITRDV-UHFFFAOYSA-N 0.000 description 2
- ANOOTOPTCJRUPK-UHFFFAOYSA-N 1-iodohexane Chemical compound CCCCCCI ANOOTOPTCJRUPK-UHFFFAOYSA-N 0.000 description 2
- BLXSFCHWMBESKV-UHFFFAOYSA-N 1-iodopentane Chemical compound CCCCCI BLXSFCHWMBESKV-UHFFFAOYSA-N 0.000 description 2
- VAGQWHCVIHDRDI-UHFFFAOYSA-N 1-methyl-2,6-dioxo-3-pentyl-7-prop-2-enylpurine-8-carbaldehyde Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1N(CC=C)C(C=O)=N2 VAGQWHCVIHDRDI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- XJLOZGFIGMRYKU-UHFFFAOYSA-N 2-[8-chloro-1-(cyanomethyl)-2,6-dioxo-7-prop-2-enylpurin-3-yl]acetonitrile Chemical compound N#CCN1C(=O)N(CC#N)C(=O)C2=C1N=C(Cl)N2CC=C XJLOZGFIGMRYKU-UHFFFAOYSA-N 0.000 description 2
- BBRQSDQHDAVESH-UHFFFAOYSA-N 3-but-3-enyl-8-chloro-7h-purine-2,6-dione Chemical compound C=CCCN1C(=O)NC(=O)C2=C1N=C(Cl)N2 BBRQSDQHDAVESH-UHFFFAOYSA-N 0.000 description 2
- IWPBNHSYRXVLEI-UHFFFAOYSA-N 3-butyl-8-chloro-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC)C2=C1NC(Cl)=N2 IWPBNHSYRXVLEI-UHFFFAOYSA-N 0.000 description 2
- IWTBVKIGCDZRPL-UHFFFAOYSA-N 3-methylpentanol Chemical compound CCC(C)CCO IWTBVKIGCDZRPL-UHFFFAOYSA-N 0.000 description 2
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 2
- CQPGDDAKTTWVDD-UHFFFAOYSA-N 4-bromobutanenitrile Chemical compound BrCCCC#N CQPGDDAKTTWVDD-UHFFFAOYSA-N 0.000 description 2
- CCNKGFXFVYFQPF-UHFFFAOYSA-N 7-prop-2-enyl-3h-purine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=CN2CC=C CCNKGFXFVYFQPF-UHFFFAOYSA-N 0.000 description 2
- JHZGXRDENKJRDP-UHFFFAOYSA-N 8-chloro-3-(2-methoxyethoxymethyl)-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(COCCOC)C2=C1N(CC=C)C(Cl)=N2 JHZGXRDENKJRDP-UHFFFAOYSA-N 0.000 description 2
- XXPLSWHVETUHKP-UHFFFAOYSA-N 8-chloro-3-(4-fluorobutyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCF)C2=C1NC(Cl)=N2 XXPLSWHVETUHKP-UHFFFAOYSA-N 0.000 description 2
- ZPFIRSRQNNTEDC-UHFFFAOYSA-N 8-chloro-3-(5-fluoropentyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCF)C2=C1NC(Cl)=N2 ZPFIRSRQNNTEDC-UHFFFAOYSA-N 0.000 description 2
- ZZTKQNHOWORJOB-UHFFFAOYSA-N 8-chloro-3-(6-fluorohexyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCCF)C2=C1NC(Cl)=N2 ZZTKQNHOWORJOB-UHFFFAOYSA-N 0.000 description 2
- SRJWIBZITTYSMX-UHFFFAOYSA-N 8-chloro-3-octyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCCCC)C2=C1NC(Cl)=N2 SRJWIBZITTYSMX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- YCWUPQZAFVJPFH-UHFFFAOYSA-N 8-chloro-3-propyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCC)C2=C1NC(Cl)=N2 YCWUPQZAFVJPFH-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 2
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 208000007882 Gastritis Diseases 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 206010028116 Mucosal inflammation Diseases 0.000 description 2
- 208000011948 Multi-organ disease Diseases 0.000 description 2
- 101100310622 Mus musculus Soga1 gene Proteins 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000037902 enteropathy Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 102000053536 human HCAR2 Human genes 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000028774 intestinal disease Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
- 150000002780 morpholines Chemical class 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000002687 nonaqueous vehicle Substances 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 2
- 229940068917 polyethylene glycols Drugs 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 208000023516 stroke disease Diseases 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000003146 transient transfection Methods 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- GJQZEWPZSQUWMA-UHFFFAOYSA-N 1,3-dibutyl-2,6-dioxo-7-prop-2-enylpurine-8-carboxamide Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC=C)C(C(N)=O)=N2 GJQZEWPZSQUWMA-UHFFFAOYSA-N 0.000 description 1
- LANBTNVRWSAIOF-UHFFFAOYSA-N 1,3-dibutyl-2,6-dioxo-7-prop-2-enylpurine-8-carboxylic acid Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC=C)C(C(O)=O)=N2 LANBTNVRWSAIOF-UHFFFAOYSA-N 0.000 description 1
- JBMMFWYMLAHLOD-UHFFFAOYSA-N 1,3-dibutyl-2,6-dioxo-7h-purine-8-carbonitrile Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(C#N)=N2 JBMMFWYMLAHLOD-UHFFFAOYSA-N 0.000 description 1
- NVXIYTQSSBFAGO-UHFFFAOYSA-N 1,3-dibutyl-8-iodo-7h-purine-2,6-dione Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(I)=N2 NVXIYTQSSBFAGO-UHFFFAOYSA-N 0.000 description 1
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 1
- XZKFBZOAIGFZSU-UHFFFAOYSA-N 1-bromo-4-methylpentane Chemical compound CC(C)CCCBr XZKFBZOAIGFZSU-UHFFFAOYSA-N 0.000 description 1
- BFYPQDKZLOZOLQ-UHFFFAOYSA-N 1-bromo-6-methylheptane Chemical compound CC(C)CCCCCBr BFYPQDKZLOZOLQ-UHFFFAOYSA-N 0.000 description 1
- MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 1
- SBOVIDMPAFDRNA-UHFFFAOYSA-N 1-methyl-2,6-dioxo-3-pentyl-7-prop-2-enylpurine-8-carbonitrile Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1N(CC=C)C(C#N)=N2 SBOVIDMPAFDRNA-UHFFFAOYSA-N 0.000 description 1
- WACZKVBRIJIHLS-UHFFFAOYSA-N 1-methyl-2,6-dioxo-3-pentyl-7h-purine-8-carbonitrile Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1NC(C#N)=N2 WACZKVBRIJIHLS-UHFFFAOYSA-N 0.000 description 1
- SBNVRIGKKNNLAR-UHFFFAOYSA-N 1-methyl-3-pentyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1N(CC=C)C=N2 SBNVRIGKKNNLAR-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- HMYGQWQDAVAJDU-UHFFFAOYSA-N 2-(8-chloro-2,6-dioxo-3-propyl-7h-purin-1-yl)acetonitrile Chemical compound O=C1N(CC#N)C(=O)N(CCC)C2=C1NC(Cl)=N2 HMYGQWQDAVAJDU-UHFFFAOYSA-N 0.000 description 1
- LVVULMTWVRQPII-UHFFFAOYSA-N 2-(8-chloro-2,6-dioxo-7-prop-2-enylpurin-3-yl)acetonitrile Chemical compound N#CCN1C(=O)NC(=O)C2=C1N=C(Cl)N2CC=C LVVULMTWVRQPII-UHFFFAOYSA-N 0.000 description 1
- WMFCBPYKFPCFEQ-UHFFFAOYSA-N 2-(8-chloro-2,6-dioxo-7h-purin-3-yl)acetonitrile Chemical compound N#CCN1C(=O)NC(=O)C2=C1N=C(Cl)N2 WMFCBPYKFPCFEQ-UHFFFAOYSA-N 0.000 description 1
- JLXNWMULWUSNNZ-UHFFFAOYSA-N 2-amino-7-prop-2-enyl-3h-purin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=CN2CC=C JLXNWMULWUSNNZ-UHFFFAOYSA-N 0.000 description 1
- TZNJHEHAYZJBHR-UHFFFAOYSA-N 2-bromo-1,1,1-trifluoroethane Chemical compound FC(F)(F)CBr TZNJHEHAYZJBHR-UHFFFAOYSA-N 0.000 description 1
- JRQAAYVLPPGEHT-UHFFFAOYSA-N 2-bromoethylcyclohexane Chemical compound BrCCC1CCCCC1 JRQAAYVLPPGEHT-UHFFFAOYSA-N 0.000 description 1
- KUARIPXRZDVUJO-UHFFFAOYSA-N 2-cyclobutylethanol Chemical compound OCCC1CCC1 KUARIPXRZDVUJO-UHFFFAOYSA-N 0.000 description 1
- JEXQWCBPEWHFKC-UHFFFAOYSA-N 2-cyclopentylethanol Chemical compound OCCC1CCCC1 JEXQWCBPEWHFKC-UHFFFAOYSA-N 0.000 description 1
- QGIVNHURAZETRF-UHFFFAOYSA-N 2-cyclopropylethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1CC1 QGIVNHURAZETRF-UHFFFAOYSA-N 0.000 description 1
- PFNHSEQQEPMLNI-UHFFFAOYSA-N 2-methyl-1-pentanol Substances CCCC(C)CO PFNHSEQQEPMLNI-UHFFFAOYSA-N 0.000 description 1
- SAUGMJLWYLQPEM-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropane Chemical compound FC(F)(F)CCBr SAUGMJLWYLQPEM-UHFFFAOYSA-N 0.000 description 1
- JQSIQDBOHYJRJN-UHFFFAOYSA-N 3-butyl-1-methyl-2,6-dioxo-7-prop-2-enylpurine-8-carbaldehyde Chemical compound O=C1N(C)C(=O)N(CCCC)C2=C1N(CC=C)C(C=O)=N2 JQSIQDBOHYJRJN-UHFFFAOYSA-N 0.000 description 1
- JIZUFZVHCNNQRI-UHFFFAOYSA-N 3-butyl-1-methyl-2,6-dioxo-7h-purine-8-carbonitrile Chemical compound O=C1N(C)C(=O)N(CCCC)C2=C1NC(C#N)=N2 JIZUFZVHCNNQRI-UHFFFAOYSA-N 0.000 description 1
- FGPKSSGBSMPIBX-UHFFFAOYSA-N 3-butyl-1-methyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CCCC)C2=C1N(CC=C)C=N2 FGPKSSGBSMPIBX-UHFFFAOYSA-N 0.000 description 1
- XWNQUIUEIJAFNS-UHFFFAOYSA-N 3-butyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC)C2=C1N(CC=C)C=N2 XWNQUIUEIJAFNS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ISBNDFWSSCIEHO-UHFFFAOYSA-N 3-cyclopropylpropan-1-ol Chemical compound OCCCC1CC1 ISBNDFWSSCIEHO-UHFFFAOYSA-N 0.000 description 1
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- QLYOMZBBODOOKU-UHFFFAOYSA-N 4-(8-chloro-1-methyl-2,6-dioxo-7h-purin-3-yl)butanenitrile Chemical compound O=C1N(C)C(=O)N(CCCC#N)C2=C1NC(Cl)=N2 QLYOMZBBODOOKU-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- DMAYBPBPEUFIHJ-UHFFFAOYSA-N 4-bromobut-1-ene Chemical compound BrCCC=C DMAYBPBPEUFIHJ-UHFFFAOYSA-N 0.000 description 1
- LPNANKDXVBMDKE-UHFFFAOYSA-N 5-bromopent-1-ene Chemical compound BrCCCC=C LPNANKDXVBMDKE-UHFFFAOYSA-N 0.000 description 1
- BBBNHHFFABZOEK-UHFFFAOYSA-N 6-bromo-2,2-dimethylhexanenitrile Chemical compound N#CC(C)(C)CCCCBr BBBNHHFFABZOEK-UHFFFAOYSA-N 0.000 description 1
- FKYWXMWGXQCPIL-UHFFFAOYSA-N 7-benzyl-3-butyl-1-ethylpurine-2,6-dione Chemical compound C1=2C(=O)N(CC)C(=O)N(CCCC)C=2N=CN1CC1=CC=CC=C1 FKYWXMWGXQCPIL-UHFFFAOYSA-N 0.000 description 1
- PPGCOAABDKNNMU-UHFFFAOYSA-N 7-benzyl-3-butylpurine-2,6-dione Chemical compound C1=2C(=O)NC(=O)N(CCCC)C=2N=CN1CC1=CC=CC=C1 PPGCOAABDKNNMU-UHFFFAOYSA-N 0.000 description 1
- XDUTVTQACWYOMX-UHFFFAOYSA-N 7-benzyl-3h-purine-2,6-dione Chemical compound C1=2C(=O)NC(=O)NC=2N=CN1CC1=CC=CC=C1 XDUTVTQACWYOMX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XYCJASBWORWJRB-UHFFFAOYSA-N 8-bromo-1-methyl-3-pentyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CCCCC)C2=C1NC(Br)=N2 XYCJASBWORWJRB-UHFFFAOYSA-N 0.000 description 1
- NAKWNXNAVSVBQI-UHFFFAOYSA-N 8-chloro-1-methyl-7-prop-2-enyl-3-(2-trimethylsilylethoxymethyl)purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(COCC[Si](C)(C)C)C2=C1N(CC=C)C(Cl)=N2 NAKWNXNAVSVBQI-UHFFFAOYSA-N 0.000 description 1
- NBDATXHOULWTFU-UHFFFAOYSA-N 8-chloro-1-propyl-3-(2,2,2-trifluoroethyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C(=O)N(CC(F)(F)F)C2=C1NC(Cl)=N2 NBDATXHOULWTFU-UHFFFAOYSA-N 0.000 description 1
- BBZHICDGEBLPMG-UHFFFAOYSA-N 8-chloro-3-(2-cyclobutylethyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC(Cl)=NC=2N1CCC1CCC1 BBZHICDGEBLPMG-UHFFFAOYSA-N 0.000 description 1
- LUAXNAHNUUTNCH-UHFFFAOYSA-N 8-chloro-3-(2-cyclohexylethyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC(Cl)=NC=2N1CCC1CCCCC1 LUAXNAHNUUTNCH-UHFFFAOYSA-N 0.000 description 1
- KNVKHDFQCCPYGP-UHFFFAOYSA-N 8-chloro-3-(2-methoxyethoxymethyl)-1-methyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(COCCOC)C2=C1N(CC=C)C(Cl)=N2 KNVKHDFQCCPYGP-UHFFFAOYSA-N 0.000 description 1
- ICEXPZLDOOBYJQ-UHFFFAOYSA-N 8-chloro-3-(3-cyclopropylpropyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC(Cl)=NC=2N1CCCC1CC1 ICEXPZLDOOBYJQ-UHFFFAOYSA-N 0.000 description 1
- NCLSUDNPUAQNGG-UHFFFAOYSA-N 8-chloro-3-(3-methylbutyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCC(C)C)C2=C1NC(Cl)=N2 NCLSUDNPUAQNGG-UHFFFAOYSA-N 0.000 description 1
- ROWFLYXVLHWFCX-UHFFFAOYSA-N 8-chloro-3-(4,4,4-trifluorobutyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC(F)(F)F)C2=C1NC(Cl)=N2 ROWFLYXVLHWFCX-UHFFFAOYSA-N 0.000 description 1
- VFBZAINUYJHWPP-UHFFFAOYSA-N 8-chloro-3-(4-fluorobutyl)-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCF)C2=C1N(CC=C)C(Cl)=N2 VFBZAINUYJHWPP-UHFFFAOYSA-N 0.000 description 1
- ZNVJRZYGHAXJHF-UHFFFAOYSA-N 8-chloro-3-(6-methylheptyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCC(C)C)C2=C1NC(Cl)=N2 ZNVJRZYGHAXJHF-UHFFFAOYSA-N 0.000 description 1
- FXJKFMLZQAMACQ-UHFFFAOYSA-N 8-chloro-3-decyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCCCCCC)C2=C1NC(Cl)=N2 FXJKFMLZQAMACQ-UHFFFAOYSA-N 0.000 description 1
- JYEATXXCQAWVKU-UHFFFAOYSA-N 8-chloro-3-ethyl-1-methyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC)C2=C1NC(Cl)=N2 JYEATXXCQAWVKU-UHFFFAOYSA-N 0.000 description 1
- HUVQZTHDZSHNOF-UHFFFAOYSA-N 8-chloro-3-hexyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCCC)C2=C1NC(Cl)=N2 HUVQZTHDZSHNOF-UHFFFAOYSA-N 0.000 description 1
- AMLPPZIEUAPJGP-UHFFFAOYSA-N 8-chloro-7-prop-2-enyl-3-(2,2,2-trifluoroethyl)purine-2,6-dione Chemical compound O=C1NC(=O)N(CC(F)(F)F)C2=C1N(CC=C)C(Cl)=N2 AMLPPZIEUAPJGP-UHFFFAOYSA-N 0.000 description 1
- NWDACWZOOXZVRV-UHFFFAOYSA-N 8-chloro-7-prop-2-enyl-3-(2-trimethylsilylethoxymethyl)purine-2,6-dione Chemical compound O=C1NC(=O)N(COCC[Si](C)(C)C)C2=C1N(CC=C)C(Cl)=N2 NWDACWZOOXZVRV-UHFFFAOYSA-N 0.000 description 1
- ZXVBJNLBSNPDQP-UHFFFAOYSA-N 8-chloro-7-prop-2-enyl-3-(4,4,4-trifluorobutyl)purine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC(F)(F)F)C2=C1N(CC=C)C(Cl)=N2 ZXVBJNLBSNPDQP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 description 1
- 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108010029320 PPi3 penicillopepsin Proteins 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WGZCUXZFISUUPR-UHFFFAOYSA-N acetonitrile;oxolane Chemical compound CC#N.C1CCOC1 WGZCUXZFISUUPR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 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 1
- 230000027455 binding Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000010036 cardiovascular benefit Effects 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- WPOPOPFNZYPKAV-UHFFFAOYSA-N cyclobutylmethanol Chemical compound OCC1CCC1 WPOPOPFNZYPKAV-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000011597 hartley guinea pig Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000044989 human HCAR3 Human genes 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 208000006278 hypochromic anemia Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 229960004184 ketamine hydrochloride Drugs 0.000 description 1
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- RSXIUVAIERKMJK-UHFFFAOYSA-N methyl 1,3-dibutyl-2,6-dioxo-7-prop-2-enylpurine-8-carboxylate Chemical compound O=C1N(CCCC)C(=O)N(CCCC)C2=C1N(CC=C)C(C(=O)OC)=N2 RSXIUVAIERKMJK-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229940069575 rompun Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 230000008733 trauma Effects 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
- 230000002792 vascular Effects 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 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
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0403282A GB0403282D0 (en) | 2004-02-14 | 2004-02-14 | Chemical compounds |
| GB0423562A GB0423562D0 (en) | 2004-10-22 | 2004-10-22 | Novel compounds |
| GB0428375A GB0428375D0 (en) | 2004-12-24 | 2004-12-24 | Novel compounds |
| PCT/EP2005/001449 WO2005077950A2 (en) | 2004-02-14 | 2005-02-10 | Medicaments with hm74a receptor activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL177051A0 IL177051A0 (en) | 2006-12-10 |
| IL177051A true IL177051A (en) | 2013-01-31 |
Family
ID=34864831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL177051A IL177051A (en) | 2004-02-14 | 2006-07-24 | Xanthine derivatives, pharmaceutical formulations comprising same, method for their preparation and use thereof in the preparation of medicaments |
Country Status (25)
| Country | Link |
|---|---|
| US (5) | US7713982B2 (enExample) |
| EP (1) | EP1781657B1 (enExample) |
| JP (2) | JP5001012B2 (enExample) |
| KR (1) | KR101100601B1 (enExample) |
| CN (2) | CN101863888B (enExample) |
| AR (1) | AR047669A1 (enExample) |
| AU (1) | AU2005212816C1 (enExample) |
| BR (1) | BRPI0507604A (enExample) |
| CA (1) | CA2556073C (enExample) |
| CY (1) | CY1114022T1 (enExample) |
| DK (1) | DK1781657T3 (enExample) |
| ES (1) | ES2406732T3 (enExample) |
| HR (1) | HRP20130406T1 (enExample) |
| IL (1) | IL177051A (enExample) |
| MA (1) | MA28357A1 (enExample) |
| MY (1) | MY148937A (enExample) |
| NO (1) | NO337281B1 (enExample) |
| NZ (1) | NZ548496A (enExample) |
| PE (1) | PE20060317A1 (enExample) |
| PL (1) | PL1781657T3 (enExample) |
| PT (1) | PT1781657E (enExample) |
| SG (1) | SG157242A1 (enExample) |
| SI (1) | SI1781657T1 (enExample) |
| TW (1) | TWI350289B (enExample) |
| WO (1) | WO2005077950A2 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL206890B1 (pl) * | 1999-11-12 | 2010-10-29 | Biogen Idec Ma | Pochodna bicykloalkilopuryny, jej zastosowanie i kompozycja leku |
| AR039385A1 (es) | 2002-04-19 | 2005-02-16 | Astrazeneca Ab | Derivados de tioxantina como inhibidores de la mieloperoxidasa |
| EP1603585A2 (en) | 2003-03-14 | 2005-12-14 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel human g-protein coupled receptor variant of hm74, hgprbmy74 |
| PE20050483A1 (es) | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
| SI1781657T1 (sl) * | 2004-02-14 | 2013-07-31 | Glaxosmithkline Intellectual Property Development Limited | Zdravila z aktivnostjo na receptor hm74a |
| NZ555320A (en) | 2004-12-03 | 2010-11-26 | Schering Corp | Substituted piperazines as CB1 antagonists |
| MY140748A (en) | 2004-12-06 | 2010-01-15 | Astrazeneca Ab | Novel pyrrolo [3,2-d] pyrimidin-4-one derivatives and their use in therapy |
| PE20060949A1 (es) | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| AU2006247695B2 (en) | 2005-05-17 | 2012-08-09 | Merck Sharp & Dohme Corp. | Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia |
| US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| US7750015B2 (en) | 2005-05-17 | 2010-07-06 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| AU2006259137B2 (en) * | 2005-06-14 | 2010-04-01 | F. Hoffmann-La Roche Ag | Anthranilic acid derivatives |
| HRP20110295T1 (hr) | 2005-06-28 | 2011-05-31 | Merck Sharp & Dohme Corp. | Agonisti receptora niacina, smjese koje sadržavaju takve spojeve i postupci liječenja |
| EP1912992A1 (en) * | 2005-08-10 | 2008-04-23 | SmithKline Beecham Corporation | Xanthine derivatives as selective hm74a agonists |
| CN101400682A (zh) * | 2006-01-20 | 2009-04-01 | 先灵公司 | 治疗异常脂血症的杂环烟酸受体激动剂 |
| MX2008014689A (es) * | 2006-05-23 | 2008-11-27 | Hoffmann La Roche | Derivados de piridopirimidininona. |
| TW200804383A (en) | 2006-06-05 | 2008-01-16 | Astrazeneca Ab | New compounds |
| 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 |
| CA2680775A1 (en) | 2007-03-23 | 2008-10-02 | F. Hoffmann-La Roche Ag | Aza-pyridopyrimidinone derivatives |
| 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 |
| WO2010075069A1 (en) | 2008-12-16 | 2010-07-01 | Schering Corporation | Bicyclic pyranone derivatives as nicotinic acid receptor agonists |
| EP2379547A1 (en) | 2008-12-16 | 2011-10-26 | Schering Corporation | Pyridopyrimidine derivatives and methods of use thereof |
| CN102276610B (zh) * | 2011-05-04 | 2013-01-09 | 北京工业大学 | N7-鸟嘌呤烷化物的制备方法 |
| CN103360394B (zh) * | 2013-07-29 | 2015-07-22 | 上海万巷制药有限公司 | 8-氯茶碱的制备方法 |
| BR112017016065A2 (pt) * | 2015-01-30 | 2018-04-03 | Shanton Pharma Co., Ltd. | prevenção ou tratamento de ácido úrico ou doença gotosa |
| CN104892610B (zh) * | 2015-05-27 | 2016-08-24 | 福建师范大学 | 一种8-酯基咖啡因衍生物的制备方法 |
| CN105622610A (zh) * | 2016-03-28 | 2016-06-01 | 浙江诚意药业股份有限公司 | 一种黄嘌呤化合物的制备方法 |
| WO2018019911A1 (en) | 2016-07-27 | 2018-02-01 | Hartis-Pharma Sarl | Therapeutic combinations to treat red blood cell disorders |
| CN106632061B (zh) * | 2016-11-23 | 2020-07-24 | 上海皓元医药股份有限公司 | 一种1-(4-苯基-1-烷基-1h-咪唑-2-基)乙酮及其衍生物的合成方法 |
| MX2019008230A (es) | 2017-01-10 | 2019-10-24 | Bayer Ag | Derivados heterociclicos como agentes de control de plagas. |
| JP2022549807A (ja) * | 2019-09-25 | 2022-11-29 | ゴールドフィンチ バイオ，インク． | キサンチンｃｂ１阻害物質 |
| 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 |
| CN113262882B (zh) * | 2021-07-21 | 2021-09-17 | 北京矿冶研究总院 | 阳离子捕收剂、制备方法及在磷矿反浮选中的应用 |
| AU2024229006A1 (en) * | 2023-02-27 | 2025-09-18 | Shanton Pharma Pte. Ltd. | Crystal form of 8-chloro-3-pentyl-3,7-dihydro-1h-purin-2,6-dione compound and preparation method therefor |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2797220A (en) * | 1954-12-02 | 1957-06-25 | Univ Michigan | Substituted paraxanthines |
| US4847377A (en) * | 1985-05-13 | 1989-07-11 | Schering Corporation | Substituted-2,3-dihydro-6-substituted-pyrimido[2,1-F]-purine-4,8(1H,9H)-diones |
| 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 |
| ATE230990T1 (de) | 1992-03-04 | 2003-02-15 | Cell Therapeutics Inc | Enantiomere hydroxylierte xanthinverbindungen |
| US5473070A (en) | 1992-11-16 | 1995-12-05 | Cell Therapeutics, Inc. | Substituted long chain alcohol xanthine compounds |
| US6693105B1 (en) * | 1992-11-16 | 2004-02-17 | Cell Therapeutics, Inc. | Hydroxyl-containing compounds |
| US6469017B1 (en) * | 1998-01-16 | 2002-10-22 | Cell Therapeutics, Inc. | Method of inhibiting interleukin-12 signaling |
| US5804584A (en) | 1992-11-16 | 1998-09-08 | Cell Therapeutics, Inc. | Therapeutic compounds containing a monocyclic five- to six- membered ring structure having one to two nitrogen atoms |
| 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 |
| AU1868195A (en) | 1994-01-28 | 1995-08-15 | Cell Therapeutics, Inc. | Cell signaling inhibitors |
| EP0746557A4 (en) * | 1994-02-18 | 1997-05-02 | Cell Therapeutics Inc | INTRACELLULAR SIGNALING MEDIATORS |
| US6780865B1 (en) | 1994-02-18 | 2004-08-24 | Cell Therapeutics, Inc. | Compounds having selective hydrolytic potentials |
| US6878715B1 (en) * | 1994-02-18 | 2005-04-12 | Cell Therapeutics, Inc. | Therapeutic compounds for inhibiting interleukin-12 signals and method for using same |
| US6103730A (en) * | 1994-03-24 | 2000-08-15 | Cell Therapeutics, Inc. | Amine substituted compounds |
| US5807861A (en) * | 1994-03-24 | 1998-09-15 | Cell Therapeutics, Inc. | Amine substituted xanthinyl compounds |
| US5801182A (en) | 1994-03-24 | 1998-09-01 | Cell Therapeutics, Inc. | Amine substituted compounds |
| US6323201B1 (en) | 1994-12-29 | 2001-11-27 | The Regents Of The University Of California | Compounds for inhibition of ceramide-mediated signal transduction |
| 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 |
| JP2002541258A (ja) | 1999-04-09 | 2002-12-03 | セル セラピューティクス インコーポレーテッド | インターリューキン−１２シグナルを阻害するための治療用化合物及びその使用方法 |
| US20030207901A1 (en) * | 1999-07-27 | 2003-11-06 | Cell Therapeutics, Inc. | Hydroxyl-containing compounds |
| KR100502757B1 (ko) * | 1999-08-31 | 2005-07-22 | 반더빌트유니버시티 | Ａ２ｂ 아데노신 수용체의 선택적인 길항제 |
| EP1305328A2 (en) * | 2000-07-21 | 2003-05-02 | Mark B. Lyles | Materials and methods for binding nucleic acids to surfaces |
| FR2812482B1 (fr) * | 2000-07-28 | 2003-01-24 | Inside Technologies | Dispositif electronique portable comprenant plusieurs circuits integres sans contact |
| JP2004512278A (ja) * | 2000-09-19 | 2004-04-22 | ノビムーヌ ソシエテ アノニム | 新規な免疫調節剤、免疫阻害剤、及び抗炎症剤としてのスタチン（ＨＭＧ−ＣｏＡリダクターゼ阻害剤） |
| US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
| HU230384B1 (hu) * | 2001-02-24 | 2016-03-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xantinszármazékok, előállításuk és alkalmazásuk gyógyszerként |
| US20040254224A1 (en) * | 2001-04-11 | 2004-12-16 | Foord Steven Michael | Medicaments |
| SI1781657T1 (sl) | 2004-02-14 | 2013-07-31 | Glaxosmithkline Intellectual Property Development Limited | Zdravila z aktivnostjo na receptor hm74a |
| US20090209561A1 (en) * | 2004-10-22 | 2009-08-20 | Richard Jonathan Daniel Hatley | Xanthine Derivatives with HM74A Receptor Activity |
| WO2006045564A1 (en) | 2004-10-22 | 2006-05-04 | Smithkline Beecham Corporation | Xanthine derivatives with hm74a receptor activity |
| EP1912992A1 (en) | 2005-08-10 | 2008-04-23 | SmithKline Beecham Corporation | Xanthine derivatives as selective hm74a agonists |
| EP1939197A1 (en) * | 2006-12-22 | 2008-07-02 | Schwarz Pharma Ag | 8-ethinylxanthine derivatives as selective A2A receptor antagonists |
| 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 |
| US20110065676A1 (en) * | 2009-06-24 | 2011-03-17 | Schering Corporation | Combination therapies comprising par1 antagonists with nar agonists |
-
2005
- 2005-02-10 SI SI200531730T patent/SI1781657T1/sl unknown
- 2005-02-10 WO PCT/EP2005/001449 patent/WO2005077950A2/en not_active Ceased
- 2005-02-10 ES ES05707363T patent/ES2406732T3/es not_active Expired - Lifetime
- 2005-02-10 NZ NZ548496A patent/NZ548496A/en not_active IP Right Cessation
- 2005-02-10 AU AU2005212816A patent/AU2005212816C1/en not_active Ceased
- 2005-02-10 SG SG200803771-5A patent/SG157242A1/en unknown
- 2005-02-10 KR KR1020067016277A patent/KR101100601B1/ko not_active Expired - Fee Related
- 2005-02-10 BR BRPI0507604-8A patent/BRPI0507604A/pt not_active Application Discontinuation
- 2005-02-10 EP EP05707363A patent/EP1781657B1/en not_active Expired - Lifetime
- 2005-02-10 DK DK05707363.7T patent/DK1781657T3/da active
- 2005-02-10 CN CN2010102007350A patent/CN101863888B/zh not_active Expired - Fee Related
- 2005-02-10 HR HRP20130406TT patent/HRP20130406T1/hr unknown
- 2005-02-10 PL PL05707363T patent/PL1781657T3/pl unknown
- 2005-02-10 CA CA2556073A patent/CA2556073C/en not_active Expired - Fee Related
- 2005-02-10 JP JP2006552565A patent/JP5001012B2/ja not_active Expired - Fee Related
- 2005-02-10 CN CN2005800114336A patent/CN101103030B/zh not_active Expired - Fee Related
- 2005-02-10 PT PT57073637T patent/PT1781657E/pt unknown
- 2005-02-10 US US10/589,474 patent/US7713982B2/en not_active Expired - Fee Related
- 2005-02-11 PE PE2005000170A patent/PE20060317A1/es not_active Application Discontinuation
- 2005-02-14 TW TW094104133A patent/TWI350289B/zh not_active IP Right Cessation
- 2005-02-14 AR ARP050100512A patent/AR047669A1/es not_active Application Discontinuation
- 2005-02-14 MY MYPI20050527A patent/MY148937A/en unknown
-
2006
- 2006-07-24 IL IL177051A patent/IL177051A/en not_active IP Right Cessation
- 2006-08-11 MA MA29262A patent/MA28357A1/fr unknown
- 2006-09-13 NO NO20064151A patent/NO337281B1/no not_active IP Right Cessation
-
2008
- 2008-02-12 JP JP2008030344A patent/JP5020848B2/ja not_active Expired - Fee Related
-
2009
- 2009-09-02 US US12/552,649 patent/US8394808B2/en not_active Expired - Fee Related
-
2010
- 2010-03-04 US US12/717,349 patent/US8268839B2/en not_active Expired - Fee Related
-
2013
- 2013-02-06 US US13/760,423 patent/US20130150383A1/en not_active Abandoned
- 2013-05-29 CY CY20131100430T patent/CY1114022T1/el unknown
-
2014
- 2014-11-21 US US14/549,721 patent/US20150080418A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1781657B1 (en) | Medicaments with hm74a receptor activity | |
| EP1912991B1 (en) | Xanthine derivatives as selective hm74a agonists | |
| WO2006045564A1 (en) | Xanthine derivatives with hm74a receptor activity | |
| EP1805180A1 (en) | Xanthine derivatives with hm74a receptor activity | |
| WO2007017265A1 (en) | Xanthine derivatives as selective hm74a agonists | |
| EP1689699A2 (en) | Anthranilic acid derivatives and their use as activators of the hm74a receptor | |
| US20080200468A1 (en) | 2-Substituted 5-Membered Heteroaryl Carboxylates as Hm74a Receptor Agonists | |
| RU2395511C2 (ru) | Новые соединения | |
| HK1104530B (en) | Medicaments with hm74a receptor activity | |
| MXPA06009269A (en) | Novel compounds | |
| ZA200605785B (en) | Novel compounds | |
| HK1116779B (en) | Xanthine derivatives as selective hm74a agonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |