ES2690082T3 - Derivados de purina para el tratamiento de infecciones virales - Google Patents
Derivados de purina para el tratamiento de infecciones virales Download PDFInfo
- Publication number
- ES2690082T3 ES2690082T3 ES12784574.1T ES12784574T ES2690082T3 ES 2690082 T3 ES2690082 T3 ES 2690082T3 ES 12784574 T ES12784574 T ES 12784574T ES 2690082 T3 ES2690082 T3 ES 2690082T3
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- alkyl
- mmol
- mixture
- compound
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- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 9
- 208000036142 Viral infection Diseases 0.000 title description 5
- 230000009385 viral infection Effects 0.000 title description 4
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 16
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
- 239000012453 solvate Substances 0.000 claims abstract description 10
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- -1 pyridacinyl Chemical group 0.000 claims abstract description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 3
- AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims abstract description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 3
- 125000002541 furyl group Chemical group 0.000 claims abstract description 3
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims abstract description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims abstract description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims abstract description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 3
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 claims abstract description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 104
- 239000000203 mixture Substances 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- 238000000034 method Methods 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
- 238000005160 1H NMR spectroscopy Methods 0.000 description 57
- 239000007787 solid Substances 0.000 description 47
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
- 239000000243 solution Substances 0.000 description 42
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- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000003786 synthesis reaction Methods 0.000 description 37
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- 230000002829 reductive effect Effects 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000004811 liquid chromatography Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000012043 crude product Substances 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 22
- 239000013067 intermediate product Substances 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 229910020175 SiOH Inorganic materials 0.000 description 19
- 230000001788 irregular Effects 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 102000002689 Toll-like receptor Human genes 0.000 description 13
- 108020000411 Toll-like receptor Proteins 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 108010050904 Interferons Proteins 0.000 description 11
- 102000014150 Interferons Human genes 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 235000019253 formic acid Nutrition 0.000 description 11
- 229940079322 interferon Drugs 0.000 description 11
- 239000003643 water by type Substances 0.000 description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 9
- 239000005695 Ammonium acetate Substances 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 235000019257 ammonium acetate Nutrition 0.000 description 9
- 229940043376 ammonium acetate Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229910052739 hydrogen Chemical group 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 238000010408 sweeping Methods 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 235000015320 potassium carbonate Nutrition 0.000 description 8
- 150000003212 purines Chemical class 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 7
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- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
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- 229910000069 nitrogen hydride Inorganic materials 0.000 description 7
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- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
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- QYYZXEPEVBXNNA-QGZVFWFLSA-N (1R)-2-acetyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-5-methylsulfonyl-1,3-dihydroisoindole-1-carboxamide Chemical compound C(C)(=O)N1[C@H](C2=CC=C(C=C2C1)S(=O)(=O)C)C(=O)NC1=CC=C(C=C1)C(C(F)(F)F)(C(F)(F)F)O QYYZXEPEVBXNNA-QGZVFWFLSA-N 0.000 description 4
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- 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
- A61P37/02—Immunomodulators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
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- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11188511 | 2011-11-09 | ||
| EP11188511 | 2011-11-09 | ||
| PCT/EP2012/072090 WO2013068438A1 (en) | 2011-11-09 | 2012-11-08 | Purine derivatives for the treatment of viral infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2690082T3 true ES2690082T3 (es) | 2018-11-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12784574.1T Active ES2690082T3 (es) | 2011-11-09 | 2012-11-08 | Derivados de purina para el tratamiento de infecciones virales |
Country Status (29)
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