FI66383C - Foerfarande foer framstaellning av farmakologiskt aktiva xantinderivat - Google Patents
Foerfarande foer framstaellning av farmakologiskt aktiva xantinderivat Download PDFInfo
- Publication number
- FI66383C FI66383C FI783126A FI783126A FI66383C FI 66383 C FI66383 C FI 66383C FI 783126 A FI783126 A FI 783126A FI 783126 A FI783126 A FI 783126A FI 66383 C FI66383 C FI 66383C
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- compound
- pyrimidinedione
- preparation
- hydroxypropyl
- Prior art date
Links
- 230000006611 pharmacological activation Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 79
- 238000002360 preparation method Methods 0.000 claims description 55
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 58
- IUBYSRVXJPSEMI-UHFFFAOYSA-N 1,8-dimethyl-3-phenyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)C=2NC(C)=NC=2N1C1=CC=CC=C1 IUBYSRVXJPSEMI-UHFFFAOYSA-N 0.000 description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 43
- 239000013078 crystal Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 31
- 229960000278 theophylline Drugs 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 238000012360 testing method Methods 0.000 description 26
- 239000000203 mixture Substances 0.000 description 25
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 22
- 206010020751 Hypersensitivity Diseases 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 108010058846 Ovalbumin Proteins 0.000 description 18
- 206010006482 Bronchospasm Diseases 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 14
- 230000002052 anaphylactic effect Effects 0.000 description 14
- VPIHNUGBRDLODE-UHFFFAOYSA-N 5,6-diamino-3-methyl-1-phenylpyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)C(N)=C(N)N1C1=CC=CC=C1 VPIHNUGBRDLODE-UHFFFAOYSA-N 0.000 description 12
- WISDTWPPWMBQRP-UHFFFAOYSA-N 6-amino-1-(2-hydroxypropyl)-3-methylpyrimidine-2,4-dione Chemical compound CC(O)CN1C(N)=CC(=O)N(C)C1=O WISDTWPPWMBQRP-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000013543 active substance Substances 0.000 description 11
- 230000007815 allergy Effects 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- -1 3,7-dihydro-1,8-dimethyl-3- (2-hydroxypropyl) -1H-purine-2,6-dione ion Chemical class 0.000 description 10
- 208000009079 Bronchial Spasm Diseases 0.000 description 10
- 208000014181 Bronchial disease Diseases 0.000 description 10
- 208000026935 allergic disease Diseases 0.000 description 10
- 208000006673 asthma Diseases 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229960000265 cromoglicic acid Drugs 0.000 description 9
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 230000002685 pulmonary effect Effects 0.000 description 9
- OLYIXZPUAUTPRG-UHFFFAOYSA-N 5,6-diamino-1-(2-hydroxypropyl)-3-methylpyrimidine-2,4-dione Chemical compound CC(O)CN1C(N)=C(N)C(=O)N(C)C1=O OLYIXZPUAUTPRG-UHFFFAOYSA-N 0.000 description 8
- BPRQNGWKKPDVLX-UHFFFAOYSA-N 6-amino-3-methyl-5-nitroso-1-phenylpyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)C(N=O)=C(N)N1C1=CC=CC=C1 BPRQNGWKKPDVLX-UHFFFAOYSA-N 0.000 description 8
- 206010002198 Anaphylactic reaction Diseases 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 8
- 208000003455 anaphylaxis Diseases 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 229940092253 ovalbumin Drugs 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- QEGWGQWGRGCLLC-UHFFFAOYSA-N 3-(2-hydroxypropyl)-1,8-dimethyl-7H-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC(O)C)C2=C1NC(C)=N2 QEGWGQWGRGCLLC-UHFFFAOYSA-N 0.000 description 7
- WHEPPORDOVLOOT-UHFFFAOYSA-N 6-amino-1-(2-hydroxypropyl)pyrimidine-2,4-dione Chemical compound CC(O)CN1C(N)=CC(=O)NC1=O WHEPPORDOVLOOT-UHFFFAOYSA-N 0.000 description 7
- 230000036783 anaphylactic response Effects 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 230000007885 bronchoconstriction Effects 0.000 description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- 230000000069 prophylactic effect Effects 0.000 description 7
- 239000002893 slag Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- LRFVTYWOQMYALW-UHFFFAOYSA-N Xanthine Natural products O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229960001340 histamine Drugs 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- KZXZZGLYAPSKGB-UHFFFAOYSA-N 3-(2-hydroxypropyl)-8-methyl-1-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC)C(=O)N(CC(C)O)C2=C1NC(C)=N2 KZXZZGLYAPSKGB-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 230000003266 anti-allergic effect Effects 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000004061 bleaching Methods 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 210000000621 bronchi Anatomy 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- HUUBMDVALDIOTQ-UHFFFAOYSA-N 5,6-diamino-1-(2-hydroxypropyl)-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N)=C(N)N(CC(C)O)C1=O HUUBMDVALDIOTQ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 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 4
- 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 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 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 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 206010070834 Sensitisation Diseases 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 239000013566 allergen Substances 0.000 description 4
- 230000000172 allergic effect Effects 0.000 description 4
- 230000002804 anti-anaphylactic effect Effects 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000008313 sensitization Effects 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 206010039085 Rhinitis allergic Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 208000030961 allergic reaction Diseases 0.000 description 3
- 201000010105 allergic rhinitis Diseases 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 235000010216 calcium carbonate Nutrition 0.000 description 3
- 230000002254 contraceptive effect Effects 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 229960004793 sucrose Drugs 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical class CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- XOXXFRIKPZNUFO-UHFFFAOYSA-N (2-cyanoacetyl) 2-cyanoacetate Chemical compound N#CCC(=O)OC(=O)CC#N XOXXFRIKPZNUFO-UHFFFAOYSA-N 0.000 description 2
- MTBUJUHRXVGLEF-UHFFFAOYSA-N 1,8-dimethyl-3-(2-methylbutyl)-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC(C)CC)C2=C1NC(C)=N2 MTBUJUHRXVGLEF-UHFFFAOYSA-N 0.000 description 2
- LXHXXJWJTAOGNV-UHFFFAOYSA-N 1,8-dimethyl-3-propyl-7H-purine-2,6-dione Chemical compound CC1=NC=2N(C(N(C(C=2N1)=O)C)=O)CCC LXHXXJWJTAOGNV-UHFFFAOYSA-N 0.000 description 2
- UUSSTBFLCYYYKK-UHFFFAOYSA-N 1-(2-hydroxypropyl)-3-propylurea Chemical compound CCCNC(=O)NCC(C)O UUSSTBFLCYYYKK-UHFFFAOYSA-N 0.000 description 2
- ZWBVEGRNXSLHFM-UHFFFAOYSA-N 1-methyl-3-phenyl-8-propyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)C=2NC(CCC)=NC=2N1C1=CC=CC=C1 ZWBVEGRNXSLHFM-UHFFFAOYSA-N 0.000 description 2
- SQBHGDSDVWCPHN-UHFFFAOYSA-N 1-methyl-3-phenylurea Chemical compound CNC(=O)NC1=CC=CC=C1 SQBHGDSDVWCPHN-UHFFFAOYSA-N 0.000 description 2
- VHEYHMGSWDZXEN-UHFFFAOYSA-N 2-hydroxypropylurea Chemical compound CC(O)CNC(N)=O VHEYHMGSWDZXEN-UHFFFAOYSA-N 0.000 description 2
- VXCQITLHULRIHV-UHFFFAOYSA-N 6-amino-1-(2-hydroxypropyl)-3-methyl-5-nitrosopyrimidine-2,4-dione Chemical compound CC(O)CN1C(N)=C(N=O)C(=O)N(C)C1=O VXCQITLHULRIHV-UHFFFAOYSA-N 0.000 description 2
- GGJIABCZMGTCRC-UHFFFAOYSA-N 6-amino-1-(2-hydroxypropyl)-5-nitroso-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N=O)=C(N)N(CC(C)O)C1=O GGJIABCZMGTCRC-UHFFFAOYSA-N 0.000 description 2
- SDGUKDIBOTVHAM-UHFFFAOYSA-N 6-amino-3-(2-hydroxypropyl)-1-methylpyrimidine-2,4-dione Chemical compound CC(O)CN1C(=O)C=C(N)N(C)C1=O SDGUKDIBOTVHAM-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- LUMUUGRCMFYCEB-UHFFFAOYSA-N CC=NC(C(N1C)=O)=C(N)N(C2=CC=CC=C2)C1=O Chemical compound CC=NC(C(N1C)=O)=C(N)N(C2=CC=CC=C2)C1=O LUMUUGRCMFYCEB-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 239000008116 calcium stearate Substances 0.000 description 2
- 235000013539 calcium stearate Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- LKYSNWSHWDHNJX-CMDGGOBGSA-N 1,3-dimethyl-5-nitro-6-[(e)-2-phenylethenyl]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C)C(\C=C\C=2C=CC=CC=2)=C1[N+]([O-])=O LKYSNWSHWDHNJX-CMDGGOBGSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- VPLZGVOSFFCKFC-UHFFFAOYSA-N 3-methyluracil Chemical compound CN1C(=O)C=CNC1=O VPLZGVOSFFCKFC-UHFFFAOYSA-N 0.000 description 1
- CSHWHTVLAPXUTQ-UHFFFAOYSA-N 6-amino-1-(2-hydroxypropyl)-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C=C(N)N(CC(C)O)C1=O CSHWHTVLAPXUTQ-UHFFFAOYSA-N 0.000 description 1
- QZMWMPFVPMZGTH-UHFFFAOYSA-N 6-amino-3-methyl-1-phenylpyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)C=C(N)N1C1=CC=CC=C1 QZMWMPFVPMZGTH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 101800004419 Cleaved form Proteins 0.000 description 1
- 239000008709 Curare Substances 0.000 description 1
- 241000509579 Draco Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101000749842 Homo sapiens Leukocyte cell-derived chemotaxin 1 Proteins 0.000 description 1
- 102100040448 Leukocyte cell-derived chemotaxin 1 Human genes 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 101100064676 Mus musculus Edem1 gene Proteins 0.000 description 1
- RYXPMWYHEBGTRV-UHFFFAOYSA-N Omeprazole sodium Chemical compound [Na+].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C RYXPMWYHEBGTRV-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 229910019020 PtO2 Inorganic materials 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 241000277284 Salvelinus fontinalis Species 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940127225 asthma medication Drugs 0.000 description 1
- 210000003912 basophilic leucocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000007931 coated granule Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940109248 cromoglycate Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000007911 effervescent powder Substances 0.000 description 1
- OIMXTYUHMBQQJM-UHFFFAOYSA-N ergone Natural products C1=CC2=CC(=O)CCC2(C)C2C1=C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OIMXTYUHMBQQJM-UHFFFAOYSA-N 0.000 description 1
- OIMXTYUHMBQQJM-HSVWHVBGSA-N ergosta-4,6,8(14),22-tetraen-3-one Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2C1=C1CC[C@H]([C@H](C)/C=C/[C@H](C)C(C)C)[C@@]1(C)CC2 OIMXTYUHMBQQJM-HSVWHVBGSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000007686 potassium 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
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7711581 | 1977-10-14 | ||
| SE7711581A SE416810C (sv) | 1977-10-14 | 1977-10-14 | Forfarande for framstellning av xantinderivat med antiallergisk aktivitet |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI783126A7 FI783126A7 (fi) | 1979-04-15 |
| FI66383B FI66383B (fi) | 1984-06-29 |
| FI66383C true FI66383C (fi) | 1984-10-10 |
Family
ID=20332576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI783126A FI66383C (fi) | 1977-10-14 | 1978-10-13 | Foerfarande foer framstaellning av farmakologiskt aktiva xantinderivat |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4233303A (cs) |
| EP (1) | EP0001735B1 (cs) |
| JP (1) | JPS5479296A (cs) |
| AT (1) | AT363491B (cs) |
| AU (1) | AU521585B2 (cs) |
| CA (1) | CA1109470A (cs) |
| CS (1) | CS208756B2 (cs) |
| DD (1) | DD139855A5 (cs) |
| DE (1) | DE2862017D1 (cs) |
| DK (1) | DK148260C (cs) |
| FI (1) | FI66383C (cs) |
| HK (1) | HK6385A (cs) |
| HU (1) | HU180219B (cs) |
| IE (1) | IE47884B1 (cs) |
| IT (1) | IT1109208B (cs) |
| NO (1) | NO147562C (cs) |
| NZ (1) | NZ188566A (cs) |
| SE (1) | SE416810C (cs) |
| SG (1) | SG85584G (cs) |
| SU (1) | SU755199A3 (cs) |
| ZA (1) | ZA785335B (cs) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE7810947L (sv) * | 1978-10-20 | 1980-04-21 | Draco Ab | 3-alkylxanthines |
| SE8002910L (sv) * | 1980-04-18 | 1981-10-19 | Draco Ab | 3,8-dialkylxantiner, forfarande for deras framstellning, beredning och metoder for behandling av kronisk obstruktiv luftvegssjukdom och kardiovaskulera sjukdomar |
| US4755517A (en) * | 1986-07-31 | 1988-07-05 | Warner-Lambert Company | Derivatives of xanthine, pharmaceutical compositions and methods of use therefor |
| US5298508A (en) * | 1988-07-19 | 1994-03-29 | The United States Of America As Represented By The Department Of Health And Human Services | Irreversible inhibitors of adenosine receptors |
| US5321029A (en) * | 1988-11-14 | 1994-06-14 | Beecham-Wuelfing Gmbh & Co.K.G. | Xanthines |
| GB8826595D0 (en) * | 1988-11-14 | 1988-12-21 | Beecham Wuelfing Gmbh & Co Kg | Active compounds |
| IT1229195B (it) * | 1989-03-10 | 1991-07-25 | Poli Ind Chimica Spa | Derivati xantinici ad attivita' broncodilatatrice e loro applicazioni terapeutiche. |
| GB8929208D0 (en) * | 1989-12-27 | 1990-02-28 | Almirall Lab | New xanthine derivatives |
| US5047534A (en) * | 1990-03-26 | 1991-09-10 | Merrell Dow Pharmaceuticals Inc. | Selective adenosine receptor agents |
| US5342841A (en) * | 1992-03-12 | 1994-08-30 | Kyowa Hakko Kogyo Co., Ltd. | Xanthine derivatives |
| US5366977A (en) * | 1992-09-29 | 1994-11-22 | The United States Of America, As Represented By The Department Of Health And Human Services | Method of treating cystic fibrosis using 8-cyclopentyl-1,3-dipropylxanthine or xanthine amino congeners |
| US5395836A (en) * | 1993-04-07 | 1995-03-07 | Kyowa Hakko Kogyo Co., Ltd. | 8-tricycloalkyl xanthine derivatives |
| GB9312853D0 (en) * | 1993-06-22 | 1993-08-04 | Euro Celtique Sa | Chemical compounds |
| US5922751A (en) * | 1994-06-24 | 1999-07-13 | Euro-Celtique, S.A. | Aryl pyrazole compound for inhibiting phosphodiesterase IV and methods of using same |
| US5591776A (en) * | 1994-06-24 | 1997-01-07 | Euro-Celtique, S.A. | Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV |
| US5661153A (en) * | 1994-07-19 | 1997-08-26 | Japan Energy Corporation | 1-arylpyrimidine derivatives and pharmaceutical use thereof |
| AU4527996A (en) * | 1994-12-13 | 1996-07-03 | Euro-Celtique S.A. | Trisubstituted thioxanthines |
| WO1996018399A1 (en) * | 1994-12-13 | 1996-06-20 | Euro-Celtique, S.A. | Aryl thioxanthines |
| US6166041A (en) * | 1995-10-11 | 2000-12-26 | Euro-Celtique, S.A. | 2-heteroaryl and 2-heterocyclic benzoxazoles as PDE IV inhibitors for the treatment of asthma |
| US6075016A (en) * | 1996-04-10 | 2000-06-13 | Euro-Celtique S.A. | 6,5-fused aromatic ring systems having enhanced phosphodiesterase IV inhibitory activity |
| US5864037A (en) | 1996-06-06 | 1999-01-26 | Euro-Celtique, S.A. | Methods for the synthesis of chemical compounds having PDE-IV inhibitory activity |
| BRPI0409699A (pt) | 2003-04-25 | 2006-04-18 | Novacardia Inc | métodos de indução do efeito diurético, de indução, manutenção ou restauração do efeito diurético de diurético não modificador de adenosina, de manutenção, restauração ou melhoria da função renal em paciente, de indução de diurese, de prevenção do inìcio de deficiência renal em paciente com sobrecarga de fluidos ou chf, de tratamento de paciente que sofre de chf e de melhoria dos resultados globais da saúde, composição farmacêutica e seus usos |
| MXPA06011823A (es) * | 2004-04-16 | 2006-12-15 | Novacardia Inc | Terapia de combinacion, que comprende un antagonista del receptor de la adenosina a1 y un inhibidor de la aldosterona. |
| US20070049757A1 (en) * | 2005-08-26 | 2007-03-01 | Rieger Jayson M | Methods for the synthesis of substituted amino uracils |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1911279A1 (de) * | 1969-03-05 | 1970-11-12 | Eckert Dr Theodor | Verfahren zur Erhoehung der Resorptionsfaehigkeit von Arzneistoffen |
| US3900474A (en) * | 1973-05-14 | 1975-08-19 | Kendall & Co | Trifluoroalkyl, fluorobenzyl, pentafluorobenzyl, fluorobenzenesulfonyl, and pentafluorobenzenesulfonyl theophyllines |
| US4061753A (en) * | 1976-02-06 | 1977-12-06 | Interx Research Corporation | Treating psoriasis with transient pro-drug forms of xanthine derivatives |
| CA1077932A (en) | 1976-03-31 | 1980-05-20 | Berlex Laboratories, Inc. | Xanthine compounds and method of treating bronchospastic and allergic diseases |
| US4120947A (en) * | 1976-03-31 | 1978-10-17 | Cooper Laboratories, Inc. | Xanthine compounds and method of treating bronchospastic and allergic diseases |
-
1977
- 1977-10-14 SE SE7711581A patent/SE416810C/sv unknown
-
1978
- 1978-09-19 ZA ZA00785335A patent/ZA785335B/xx unknown
- 1978-09-29 US US05/947,002 patent/US4233303A/en not_active Expired - Lifetime
- 1978-10-03 NZ NZ188566A patent/NZ188566A/en unknown
- 1978-10-03 DE DE7878850015T patent/DE2862017D1/de not_active Expired
- 1978-10-03 AU AU40365/78A patent/AU521585B2/en not_active Expired
- 1978-10-03 EP EP78850015A patent/EP0001735B1/en not_active Expired
- 1978-10-04 AT AT0714478A patent/AT363491B/de not_active IP Right Cessation
- 1978-10-10 CA CA313,026A patent/CA1109470A/en not_active Expired
- 1978-10-12 DD DD78208423A patent/DD139855A5/de unknown
- 1978-10-12 DK DK453778A patent/DK148260C/da not_active IP Right Cessation
- 1978-10-13 CS CS786669A patent/CS208756B2/cs unknown
- 1978-10-13 HU HU78DA359A patent/HU180219B/hu unknown
- 1978-10-13 IT IT51499/78A patent/IT1109208B/it active
- 1978-10-13 NO NO783471A patent/NO147562C/no unknown
- 1978-10-13 SU SU782675299A patent/SU755199A3/ru active
- 1978-10-13 FI FI783126A patent/FI66383C/fi not_active IP Right Cessation
- 1978-10-13 IE IE2041/78A patent/IE47884B1/en unknown
- 1978-10-14 JP JP12573978A patent/JPS5479296A/ja active Pending
-
1984
- 1984-11-29 SG SG855/84A patent/SG85584G/en unknown
-
1985
- 1985-01-24 HK HK63/85A patent/HK6385A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK148260C (da) | 1986-02-10 |
| EP0001735B1 (en) | 1982-09-01 |
| HK6385A (en) | 1985-02-01 |
| DK148260B (da) | 1985-05-20 |
| AU521585B2 (en) | 1982-04-22 |
| SE416810C (sv) | 1982-07-19 |
| SE7711581L (sv) | 1979-04-15 |
| IE47884B1 (en) | 1984-07-11 |
| FI66383B (fi) | 1984-06-29 |
| HU180219B (en) | 1983-02-28 |
| ATA714478A (de) | 1980-09-15 |
| AU4036578A (en) | 1980-04-17 |
| IE782041L (en) | 1979-04-14 |
| AT363491B (de) | 1981-08-10 |
| US4233303A (en) | 1980-11-11 |
| CA1109470A (en) | 1981-09-22 |
| EP0001735A1 (en) | 1979-05-02 |
| CS208756B2 (en) | 1981-09-15 |
| SE416810B (sv) | 1981-02-09 |
| NO147562B (no) | 1983-01-24 |
| IT1109208B (it) | 1985-12-16 |
| IT7851499A0 (it) | 1978-10-13 |
| NO147562C (no) | 1983-05-18 |
| SG85584G (en) | 1985-06-07 |
| DD139855A5 (de) | 1980-01-23 |
| DE2862017D1 (en) | 1982-10-28 |
| NO783471L (no) | 1979-04-18 |
| NZ188566A (en) | 1984-07-06 |
| SU755199A3 (en) | 1980-08-07 |
| ZA785335B (en) | 1979-09-26 |
| FI783126A7 (fi) | 1979-04-15 |
| DK453778A (da) | 1979-04-15 |
| JPS5479296A (en) | 1979-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI66383C (fi) | Foerfarande foer framstaellning av farmakologiskt aktiva xantinderivat | |
| TWI335918B (en) | Novel thioxanthine derivatives and medical use thereof | |
| EP0011609B1 (en) | Xanthine derivatives and pharmaceutical preparations containing these derivatives for use in the treatment of chronic obstructive airway disease and cardiac disease | |
| AU683270B2 (en) | Novel chemical compounds having PDE-IV inhibition activity | |
| EP0010531B1 (en) | 3-alkylxanthines, processes for their preparation and compositions for use in the treatment of chronic obstructive airway disease and cardiac disease | |
| CZ391891A3 (en) | Xanthine derivatives,process of their preparation and pharmaceutical preparation containing them | |
| DK161965B (da) | 6-thioxanthiner og salte deraf samt deres fremstilling og anvendelse | |
| FI69465B (fi) | Foerfarande foer framstaellning av farmakologiskt aktiva 3,8-dialkylxantiner | |
| CS262690B2 (en) | Process for preparing 1-/hydroxystyryl/-5h-2,3-benzodiazepines | |
| JPS6222771A (ja) | ５−置換−６−アミノピリミジン誘導体、組成物および使用 | |
| JP2991806B2 (ja) | ３‐（メルカプトアルキル）‐キナゾリン‐２，４（１ｈ，３ｈ）‐ジオン、その製造方法および製薬調合物 | |
| NO312400B1 (no) | Anvendelse av teofyllinderivater for behandling og profylakse av sjokktilstander, nye xantanforbindelser og deres fremstilling | |
| HU196069B (en) | Process for production of 8-/dihydropiridil-carbamoiloxi-methil/-ergolines and medical compounds containing these compositions | |
| JPH02295977A (ja) | フェニルピリミドン誘導体 | |
| US4745118A (en) | Substituted quinazoline-3-oxides providing pharmacological activity | |
| JPH05262770A (ja) | 化学的製法 | |
| JPH03294277A (ja) | ピペリジン誘導体 | |
| JP2603488B2 (ja) | 新規なエラグ酸硫酸エステル誘導体，その製法及び用途 | |
| TW467903B (en) | 2-thioxo-imidazolidin-4-one derivatives | |
| CN110776504A (zh) | 一种苯异噁唑乙氧基环丁胺衍生物及其制备方法与应用 | |
| JPH0534354B2 (cs) | ||
| JPH04128285A (ja) | キサンチン誘導体 | |
| JPS63154670A (ja) | ピリダジノン誘導体又はその塩類 | |
| JPH03106881A (ja) | キサンチン誘導体 | |
| JPH03240772A (ja) | 循環不全治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: AKTIEBOLAGET DRACO |