RU2374247C2 - Способ получения антагонистов аденозиновых рецепторов a2b и промежуточные продукты - Google Patents

Info

Publication number

RU2374247C2

RU2374247C2 RU2006117349/04A RU2006117349A RU2374247C2 RU 2374247 C2 RU2374247 C2 RU 2374247C2 RU 2006117349/04 A RU2006117349/04 A RU 2006117349/04A RU 2006117349 A RU2006117349 A RU 2006117349A RU 2374247 C2 RU2374247 C2 RU 2374247C2

Authority

RU

Russia

Prior art keywords

formula

compound

ethyl

compounds

methyl

Prior art date

2003-11-21

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• 238000000034 method Methods 0.000 title claims abstract description 100
• 102000009346 Adenosine receptors Human genes 0.000 title abstract description 21
• 108050000203 Adenosine receptors Proteins 0.000 title abstract description 21
• 239000005557 antagonist Substances 0.000 title abstract description 10
• 239000013067 intermediate product Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 350
• -1 pyrazol-4-yl Chemical group 0.000 claims abstract description 126
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 16
• 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 14
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 120
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 56
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 38
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
• 230000003993 interaction Effects 0.000 claims description 27
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 239000007864 aqueous solution Substances 0.000 claims description 19
• 239000012442 inert solvent Substances 0.000 claims description 17
• 125000001246 bromo group Chemical group Br* 0.000 claims description 14
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 claims description 13
• 239000011230 binding agent Substances 0.000 claims description 12
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 7
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 7
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• FVKPZGAIJRIYTI-UHFFFAOYSA-N N-[6-amino-4-oxo-3-(2-oxopentan-3-yl)-1,2-dihydropyrimidin-5-yl]-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound NC1=C(C(N(CN1)C(C(C)=O)CC)=O)NC(=O)C=1C=NN(C1)CC1=CC(=CC=C1)C(F)(F)F FVKPZGAIJRIYTI-UHFFFAOYSA-N 0.000 claims description 4
• JTTYIGNOWNZSHC-UHFFFAOYSA-N N-[6-amino-4-oxo-3-(2-oxopropyl)-1,2-dihydropyrimidin-5-yl]-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound NC1=C(C(N(CN1)CC(C)=O)=O)NC(=O)C=1C=NN(C1)CC1=CC(=CC=C1)C(F)(F)F JTTYIGNOWNZSHC-UHFFFAOYSA-N 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
• 239000011630 iodine Substances 0.000 claims description 3
• SYZRCDDKRGGITN-UHFFFAOYSA-N n-(6-amino-1-ethyl-2,4-dioxopyrimidin-5-yl)-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound O=C1NC(=O)N(CC)C(N)=C1NC(=O)C1=CN(CC=2C=C(C=CC=2)C(F)(F)F)N=C1 SYZRCDDKRGGITN-UHFFFAOYSA-N 0.000 claims description 3
• 238000007363 ring formation reaction Methods 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 6
• 238000004519 manufacturing process Methods 0.000 abstract description 12
• 208000006673 asthma Diseases 0.000 abstract description 11
• 230000000694 effects Effects 0.000 abstract description 8
• 239000000126 substance Substances 0.000 abstract description 8
• 206010012735 Diarrhoea Diseases 0.000 abstract description 6
• 238000013461 design Methods 0.000 abstract description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 abstract 1
• 238000006243 chemical reaction Methods 0.000 description 81
• 239000000203 mixture Substances 0.000 description 78
• 125000001424 substituent group Chemical group 0.000 description 73
• 239000000047 product Substances 0.000 description 51
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
• 125000001072 heteroaryl group Chemical group 0.000 description 46
• 125000003118 aryl group Chemical group 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• 239000000243 solution Substances 0.000 description 33
• 239000002904 solvent Substances 0.000 description 33
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 32
• 230000002829 reductive effect Effects 0.000 description 28
• 239000004480 active ingredient Substances 0.000 description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 125000003545 alkoxy group Chemical group 0.000 description 25
• 229910052736 halogen Inorganic materials 0.000 description 23
• 150000002367 halogens Chemical group 0.000 description 23
• 239000002585 base Substances 0.000 description 22
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
• 125000004181 carboxyalkyl group Chemical group 0.000 description 22
• 125000004093 cyano group Chemical group *C#N 0.000 description 22
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• 239000004615 ingredient Substances 0.000 description 21
• 125000003342 alkenyl group Chemical group 0.000 description 20
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 19
• 150000003857 carboxamides Chemical class 0.000 description 18
• 125000000623 heterocyclic group Chemical group 0.000 description 18
• 238000002360 preparation method Methods 0.000 description 18
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 17
• 239000003826 tablet Substances 0.000 description 17
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 16
• 229960005305 adenosine Drugs 0.000 description 16
• 102000005962 receptors Human genes 0.000 description 16
• 108020003175 receptors Proteins 0.000 description 16
• 239000011734 sodium Substances 0.000 description 16
• 125000000304 alkynyl group Chemical group 0.000 description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
• 150000001412 amines Chemical class 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 14
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 13
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 11
• 201000010099 disease Diseases 0.000 description 11
• 239000002798 polar solvent Substances 0.000 description 11
• 125000005110 aryl thio group Chemical group 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 239000000546 pharmaceutical excipient Substances 0.000 description 10
• 239000010802 sludge Substances 0.000 description 10
• 229930194542 Keto Chemical group 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 125000002252 acyl group Chemical group 0.000 description 9
• 125000004442 acylamino group Chemical group 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 125000004414 alkyl thio group Chemical group 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• 235000010288 sodium nitrite Nutrition 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• 150000003573 thiols Chemical group 0.000 description 9
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 8
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
• 125000004429 atom Chemical group 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
• 150000001718 carbodiimides Chemical class 0.000 description 8
• 125000005553 heteroaryloxy group Chemical group 0.000 description 8
• 125000005368 heteroarylthio group Chemical group 0.000 description 8
• 125000004468 heterocyclylthio group Chemical group 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• UBZZBQIXYQZVDV-UHFFFAOYSA-N 1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxylic acid Chemical compound C1=C(C(=O)O)C=NN1CC1=CC=CC(C(F)(F)F)=C1 UBZZBQIXYQZVDV-UHFFFAOYSA-N 0.000 description 7
• QHEMDIZENXAVRQ-UHFFFAOYSA-N 6-amino-1-ethylpyrimidine-2,4-dione Chemical compound CCN1C(N)=CC(=O)NC1=O QHEMDIZENXAVRQ-UHFFFAOYSA-N 0.000 description 7
• 229910021529 ammonia Inorganic materials 0.000 description 7
• 125000004104 aryloxy group Chemical group 0.000 description 7
• 238000007796 conventional method Methods 0.000 description 7
• 210000003630 histaminocyte Anatomy 0.000 description 7
• 150000002431 hydrogen Chemical class 0.000 description 7
• 239000003586 protic polar solvent Substances 0.000 description 7
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
• KOYXXLLNCXWUNF-UHFFFAOYSA-N 3-ethyl-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 KOYXXLLNCXWUNF-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 241000124008 Mammalia Species 0.000 description 6
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
• UNVYIXUCXYHAEA-UHFFFAOYSA-N NC1=C(C(N(CN1)C(C(C)=O)CC)=O)NC(=O)C1=NN(C=C1)CC1=CC(=CC=C1)C(F)(F)F Chemical compound NC1=C(C(N(CN1)C(C(C)=O)CC)=O)NC(=O)C1=NN(C=C1)CC1=CC(=CC=C1)C(F)(F)F UNVYIXUCXYHAEA-UHFFFAOYSA-N 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• 125000000033 alkoxyamino group Chemical group 0.000 description 6
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 6
• 235000011114 ammonium hydroxide Nutrition 0.000 description 6
• 230000027455 binding Effects 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• 150000004820 halides Chemical class 0.000 description 6
• 230000026030 halogenation Effects 0.000 description 6
• 238000005658 halogenation reaction Methods 0.000 description 6
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 6
• 239000008108 microcrystalline cellulose Substances 0.000 description 6
• 229940016286 microcrystalline cellulose Drugs 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• 239000008194 pharmaceutical composition Substances 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 229910052708 sodium Inorganic materials 0.000 description 6
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
• 235000019698 starch Nutrition 0.000 description 6
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
• FPJMMVWPHPRAMW-UHFFFAOYSA-N 6-amino-3-propyl-1h-pyrimidine-2,4-dione Chemical compound CCCN1C(=O)C=C(N)NC1=O FPJMMVWPHPRAMW-UHFFFAOYSA-N 0.000 description 5
• 208000024827 Alzheimer disease Diseases 0.000 description 5
• 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 5
• 239000007983 Tris buffer Substances 0.000 description 5
• 150000002430 hydrocarbons Chemical group 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 125000002346 iodo group Chemical group I* 0.000 description 5
• SPJDDRUDFQBAOY-UHFFFAOYSA-N n'-(3-ethyl-2,6-dioxo-1-propylpyrimidin-4-yl)-n,n-dimethylmethanimidamide Chemical compound CCCN1C(=O)C=C(N=CN(C)C)N(CC)C1=O SPJDDRUDFQBAOY-UHFFFAOYSA-N 0.000 description 5
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 5
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
• 125000003107 substituted aryl group Chemical group 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• 0 *N(C(N)=C(C(N1)=O)N=O)C1=O Chemical compound *N(C(N)=C(C(N1)=O)N=O)C1=O 0.000 description 4
• TXDXEUVACFAWQB-UHFFFAOYSA-N 5,6-diamino-1-ethyl-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N)=C(N)N(CC)C1=O TXDXEUVACFAWQB-UHFFFAOYSA-N 0.000 description 4
• YPSQTTRYMSZAGR-UHFFFAOYSA-N 6-amino-1-ethyl-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C=C(N)N(CC)C1=O YPSQTTRYMSZAGR-UHFFFAOYSA-N 0.000 description 4
• JVNIERUYZGPSCA-UHFFFAOYSA-N 6-amino-1-ethyl-5-nitroso-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N=O)=C(N)N(CC)C1=O JVNIERUYZGPSCA-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• 206010028980 Neoplasm Diseases 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 229930006000 Sucrose Natural products 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 4
• 238000001704 evaporation Methods 0.000 description 4
• 125000004470 heterocyclooxy group Chemical group 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 238000002156 mixing Methods 0.000 description 4
• CKBHZDKYMHOLNJ-UHFFFAOYSA-N n'-(3-ethyl-2,6-dioxopyrimidin-4-yl)-n,n-dimethylmethanimidamide Chemical compound CCN1C(N=CN(C)C)=CC(=O)NC1=O CKBHZDKYMHOLNJ-UHFFFAOYSA-N 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 229930195734 saturated hydrocarbon Natural products 0.000 description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 239000011593 sulfur Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 239000000454 talc Substances 0.000 description 4
• 229910052623 talc Inorganic materials 0.000 description 4
• 235000012222 talc Nutrition 0.000 description 4
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
• 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
• HEXZSEOAILCDMD-UHFFFAOYSA-N 5,6-diamino-1-ethylpyrimidine-2,4-dione Chemical compound CCN1C(N)=C(N)C(=O)NC1=O HEXZSEOAILCDMD-UHFFFAOYSA-N 0.000 description 3
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