JP2001508449A - 病原体不活化のための脆い化合物 - Google Patents
病原体不活化のための脆い化合物Info
- Publication number
- JP2001508449A JP2001508449A JP53119998A JP53119998A JP2001508449A JP 2001508449 A JP2001508449 A JP 2001508449A JP 53119998 A JP53119998 A JP 53119998A JP 53119998 A JP53119998 A JP 53119998A JP 2001508449 A JP2001508449 A JP 2001508449A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- heteroalkyl
- aryl
- heteroaryl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 181
- 244000052769 pathogen Species 0.000 title claims abstract description 66
- 230000001717 pathogenic effect Effects 0.000 title claims description 34
- 230000002779 inactivation Effects 0.000 title description 18
- 238000000034 method Methods 0.000 claims abstract description 76
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 36
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 34
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 34
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 239000012620 biological material Substances 0.000 claims abstract description 29
- 210000003743 erythrocyte Anatomy 0.000 claims abstract description 29
- 230000000415 inactivating effect Effects 0.000 claims abstract description 27
- 239000000463 material Substances 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 104
- -1 9-substituted acridine Chemical class 0.000 claims description 81
- 239000000126 substance Substances 0.000 claims description 62
- 210000004369 blood Anatomy 0.000 claims description 45
- 239000008280 blood Substances 0.000 claims description 44
- 239000012636 effector Substances 0.000 claims description 41
- 230000002441 reversible effect Effects 0.000 claims description 32
- 150000002148 esters Chemical class 0.000 claims description 27
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 27
- 150000002009 diols Chemical class 0.000 claims description 25
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 claims description 23
- 239000010836 blood and blood product Substances 0.000 claims description 20
- 229940125691 blood product Drugs 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 150000001408 amides Chemical class 0.000 claims description 19
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 16
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- 150000007970 thio esters Chemical class 0.000 claims description 15
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 13
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical group ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims description 13
- 230000027455 binding Effects 0.000 claims description 12
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- 241000700605 Viruses Species 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 210000002381 plasma Anatomy 0.000 claims description 10
- 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 claims description 8
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 210000001519 tissue Anatomy 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
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- 238000011534 incubation Methods 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 4
- 230000002152 alkylating effect Effects 0.000 claims description 4
- 238000004113 cell culture Methods 0.000 claims description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 210000003296 saliva Anatomy 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 210000004243 sweat Anatomy 0.000 claims description 4
- 210000002700 urine Anatomy 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 235000013336 milk Nutrition 0.000 claims description 3
- 210000004080 milk Anatomy 0.000 claims description 3
- 239000008267 milk Substances 0.000 claims description 3
- 210000000582 semen Anatomy 0.000 claims description 3
- ZHBWKWDAMIJZPW-UHFFFAOYSA-N 9-methoxyacridine Chemical group C1=CC=C2C(OC)=C(C=CC=C3)C3=NC2=C1 ZHBWKWDAMIJZPW-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000006143 cell culture medium Substances 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- 150000003871 sulfonates Chemical class 0.000 claims description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
- ZGVSETXHNHBTRK-OTYSSXIJSA-N solanine Chemical compound O([C@H]1[C@@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@@H]5N6C[C@@H](C)CC[C@@H]6[C@H]([C@@H]5[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O ZGVSETXHNHBTRK-OTYSSXIJSA-N 0.000 claims 3
- 150000001251 acridines Chemical class 0.000 claims 2
- RXVGBQCEAQZMLW-UHFFFAOYSA-N alpha-solanine Natural products CC1CCC2C(C)C3C(CC4C5CC=C6CC(CCC6(C)C5CCC34C)OC7OC(CO)C(O)C(OC8OC(CO)C(O)C(O)C8O)C7OC9OC(CO)C(O)C(O)C9O)N2C1 RXVGBQCEAQZMLW-UHFFFAOYSA-N 0.000 claims 2
- 150000002118 epoxides Chemical class 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- 229940031352 solanine Drugs 0.000 claims 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 1
- DWAOUXYZOSPAOH-UHFFFAOYSA-N 4-[2-(diethylamino)ethoxy]furo[3,2-g]chromen-7-one;hydrochloride Chemical compound [Cl-].O1C(=O)C=CC2=C1C=C1OC=CC1=C2OCC[NH+](CC)CC DWAOUXYZOSPAOH-UHFFFAOYSA-N 0.000 claims 1
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical group C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 claims 1
- 125000004965 chloroalkyl group Chemical group 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 238000005809 transesterification reaction Methods 0.000 claims 1
- 230000035899 viability Effects 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 25
- 238000000338 in vitro Methods 0.000 abstract description 6
- 238000001727 in vivo Methods 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 230000015556 catabolic process Effects 0.000 abstract description 4
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 229940000635 beta-alanine Drugs 0.000 description 52
- 230000002829 reductive effect Effects 0.000 description 40
- 125000005647 linker group Chemical group 0.000 description 36
- 239000000243 solution Substances 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000007062 hydrolysis Effects 0.000 description 21
- 238000006460 hydrolysis reaction Methods 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 239000007864 aqueous solution Substances 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 125000004494 ethyl ester group Chemical group 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 125000004559 acridin-9-yl group Chemical group C1=CC=CC2=NC3=CC=CC=C3C(=C12)* 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- UKOBAUFLOGFCMV-UHFFFAOYSA-N quinacrine mustard Chemical compound C1=C(Cl)C=CC2=C(NC(C)CCCN(CCCl)CCCl)C3=CC(OC)=CC=C3N=C21 UKOBAUFLOGFCMV-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 241000725303 Human immunodeficiency virus Species 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
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- 125000000524 functional group Chemical group 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 10
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- 239000002609 medium Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 241000282412 Homo Species 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000003860 storage Methods 0.000 description 9
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 8
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 8
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 8
- 229960001456 adenosine triphosphate Drugs 0.000 description 8
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/02—Blood transfusion apparatus
- A61M1/0209—Multiple bag systems for separating or storing blood components
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28033—Membrane, sheet, cloth, pad, lamellar or mat
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C07D219/08—Nitrogen atoms
- C07D219/10—Nitrogen atoms attached in position 9
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/64—Acridine or hydrogenated acridine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Anesthesiology (AREA)
- Analytical Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.物質中の病原体を不活化するための化合物であって、以下を含有する化合 物: 核酸結合部分; 核酸との共有結合の形成を可能にする、エフェクター部分;および 該核酸部分と該エフェクター部分とを共有連結している(covalently llnking) 脆い(frangible)リンカー; ここで、該物質をその意図した目的に不適切にしない条件下で、もはや該核酸 結合部分および該エフェクター部分が共有連結しないように、該脆いリンカーが 分解する。 2.前記核酸結合部分が、アクリジン、アクリジン誘導体、ソラレン、イソソ ラレンおよびソラレン誘導体からなる群より選択される、請求項1に記載の化合 物。 3.請求項1に記載の化合物であって、ここで前記脆いリンカーが、順方向(f orward)エステル、逆方向(reverse)エステル、順方向アミド、逆方向アミド、順 方向チオエステル、逆方向チオエステル、順方向および逆方向チオノエステル、 順方向および逆方向ジチオ酸、スルフェート、順方向および逆方向スルホネート 、ホスフェート、および順方向および逆方向ホスホネートの基からなる群から選 択される官能性単位から構成される、化合物。 4.エフェクター基が、アルキル化試薬である官能性単位を含む、請求項1に 記載の化合物。 5.請求項1に記載の化合物であって、ここで前記エフェクター基が、マスタ 一ド(mustard)基、マスタード基等価物、エポキシド、アルデヒドおよびホルム アルデヒドシントンからなる群より選択される官能性単位を含む、化合物。 6.以下の式を含有する化合物、ならびにその全ての塩および立体異性体(エ ナンチオマーおよびジアステレオマーを含む): ここで、R1、R2、R3、R4、R5、R6、R7およびR8は、−H、−R10、− O−R10、−NO2、−NH2、−NH−R10、−N(R10)2、−F、−Cl、 −Br、−I、−C(=O)−R10、−C(=O)−O−R10、および−O−C (=O)−R10からなる群より独立して選択され、 ここで−R10は、独立して、H、−C1-8アルキル、−C1-8ヘテロアルキル、 −アリール、−ヘテロアリール、−C1-3アルキル−アリール、−C1-3ヘテロア ルキル−アリール、−C1-3アルキル−ヘテロアリール、−C1-3ヘテロアルキル −ヘテロアリール、−アリール−C1-3アルキル、−アリール−C1-3ヘテロアル キル、−ヘテロアリール−C1-3アルキル、−ヘテロアリール−C1-3ヘテロアル キル、−C1-3アルキル−アリール−C1-3アルキル、−C1-3ヘテロアルキル− アリール−C1-3アルキル、−C1-3アルキル−ヘテロアリール−C1-3アルキル 、−C1-3アルキル−アリール−C1-3ヘテロアルキル、−C1-3ヘテロアルキル −ヘテロアリール−C1-3アルキル、−C1-3ヘテロアルキル−アリール−C1-3 ヘテロアルキル、−C1-3アルキル−ヘテロアリール−C1-3ヘテロアルキルまた は−C1-3,ヘテロアルキル−ヘテロアリール−C1-3,ヘテロアルキルであり、 R20は−Hまたは−CH3であり;そして、 R21は−R11−W−X−Eであり、 ここで−R11は、独立して、−C1-8アルキル−、−C1-8ヘテロアルキル−、 −アリール−、−ヘテロアリール−、−C1-3アルキル−アリール−、−C1-3ヘ テロアルキル−アリール−、−C1-3アルキル−ヘテロアリール−、−C1-3 ヘテロアルキル−ヘテロアリール−、−アリール−C1-3アルキル−、−アリー ル−C1-3ヘテロアルキル−、−ヘテロアリール−C1-3アルキル−、−ヘテロア リール−C1-3ヘテロアルキル−、−C1-3アルキル−アリール−C1-3アルキル −、−C1-3ヘテロアルキル−アリール−C1-3アルキル−、−C1-3アルキル− ヘテロアリール−C1-3アルキル−、−C1-3アルキル−アリール−C1-3ヘテロ アルキル−−C1-3ヘテロアルキル−ヘテロアリール−C1-3アルキル、−C1-3 ヘテロアルキル−アリール−C1-3ヘテロアルキル−、−C1-3アルキル−ヘテロ アリール−C1-3ヘテロアルキル−または−C1-3ヘテロアルキル−ヘテロアリー ル−C1-3ヘテロアルキル−であり、 Wは、独立して、−C(=O)−O−、−O−C(=O)−、−C(=S)− O−、−O−C(=S)−、−C(=S)−S−、−S−C(=S)−、−C( =O)−S−、−S−C(=O)−、−O−S(=O)2−O−、−S(=O)2 −O−、−O−S(=O)2−O−P(=O)(−OR10)−O、−P(=O) (−OR10)−O−、−O−P(=O)(−OR10)−であり、; Xは、独立して、−R11−であり;そして Eは−N(R12)2、−N(R12)(R13)、−S−R12、 および からなる群から独立して選択され; ここで−R12は−CH2CH2−Gであり、ここで各Gは独立して−Cl、−B r、−I、−O−S(=O)2−CH3、−O−S(=O)2−CH2−C6H5また は−O−S(=O)2−C6H4−CH3であり; そしてここでR13は、独立して、−C1-8アルキル、−C1-8ヘテロアルキル、 −アリール、−ヘテロアリール、−C1-3アルキル−アリール、−C1-3ヘテロア ルキル−アリール、−C1-3アルキル−ヘテロアリール、−C1-3ヘテロアルキル −ヘテロアリール、−アリール−C1-3アルキル、−アリール−C1-3ヘテロアル キル、−ヘテロアリール−C1-3アルキル、−ヘテロアリール−C1-3ヘテロアル キル、−C1-3アルキル−アリール−C1-3アルキル、−C1-3ヘテロ アルキル−アリール−C1-3アルキル、−C1-3アルキル−ヘテロアリール−C1- 3 アルキル、−C1-3アルキル−アリール−C1-3ヘテロアルキル、−C1-3ヘテロ アルキル−ヘテロアリール−C1-3アルキル、−C1-3ヘテロアルキル−アリール −C1-3ヘテロアルキル、−C1-3アルキル−ヘテロアリール−C1-3ヘテロアル キルまたは−C1-3ヘテロアルキル−ヘテロアリール−C1-3ヘテロアルキルであ る。 7.以下の式を有する化合物、ならびにその全ての塩および立体異性体(エナ ンチオマーおよびジアステレオマーを含む): ここでR44、R55、R3、R4、R5およびR8のうち少なくとも1つが−V−W −X−Eであり、そして余剰のR44、R55、R3、R4、R5およびR8が−H、− R10、−O−R10、−NO2、−NH2、−NH−R10、−N(R10)2、−F、 −Cl、−Br、−I、−C(=O)−R10、−C(=O)−O−R10、および −O−C(=O)−R10からなる群より独立して選択され、 ここで−R10は、独立して、H、−C1-8アルキル、−C1-8ヘテロアルキル、 −アリール、−ヘテロアリール、−C1-3アルキル−アリール、−C1-3ヘテロア ルキル−アリール、−C1-3アルキル−ヘテロアリール、−C1-3ヘテロアルキル −ヘテロアリール、−アリール−C1-3アルキル、−アリール−C1-3ヘテロアル キル、−ヘテロアリール−C1-3アルキル、−ヘテロアリール−C1-3ヘテロアル キル、−C1-3アルキル−アリール−C1-3アルキル、−C1-3ヘテロアルキル− アリール−C1-3アルキル、−C1-3アルキル−ヘテロアリール−C1-3アルキル 、−C1-3アルキル−アリール−C1-3ヘテロアルキル、−C1-3ヘテロアルキル −ヘテロアリール−C1-3アルキル、−C1-3ヘテロアルキル−アリール−C1-3 ヘテロアルキル、−C1-3アルキル−ヘテロアリール−C1-3 ヘテロアルキルまたは−C1-3ヘテロアルキル−ヘテロアリール−C1-3ヘテロア ルキルであり; Vは、独立して、−R11−、−NH−R11−または−N(CH3)−R11−で あり、ここで−R11−は、独立して、−C1-8アルキル−、−C1-8ヘテロアルキ ル−、−アリール−、−ヘテロアリール−、−C1-3アルキル−アリール−、− C1-3ヘテロアルキル−アリール−、−C1-3アルキル−ヘテロアリール−、−C1-3 ヘテロアルキル−ヘテロアリール−、−アリール−C1-3アルキル−、−アリ ール−C1-3ヘテロアルキル−、−ヘテロアリール−C1-3アルキル−、−ヘテロ アリール−C1-3ヘテロアルキル−、−C1-3アルキル−アリール−C1-3アルキ ル−、−C1-3ヘテロアルキル−アリール−C1-3アルキル−、−C1-3アルキル −ヘテロアリール−C1-3アルキル−、−C1-3アルキル−アリール−C1-3ヘテ ロアルキル−、−C1-3ヘテロアルキル−ヘテロアリール−C1-3アルキル−、− C1-3ヘテロアルキル−アリール−C1-3ヘテロアルキル−、−C1-3アルキル− ヘテロアリール−C1-3ヘテロアルキル−または−C1-3ヘテロアルキル−ヘテロ アリール−C1-3ヘテロアルキル−であり; Wは、独立して、−C(=O)−O−、−O−C(=O)−、−C(=S)− O−、−O−C(=S)−、−C(=S)−S−、−S−C(=S)−、−C( =O)−S−、−S−C(=O)−、−O−S(=O)2−O−、−S(=O)2 −O−、−O−S(=O)2−、−C(=O)−NR10−、−NR10−C(=O )−、−O−P(=O)(−OR10)−O−、−P(=O)(−OR10)−O− 、−O−P(=O)(−OR10)−であり、; Xは、独立して、−R11−であり;そして Eは−N(R12)2、−N(R12)(R13)、−S−R12、 および からなる群から独立して選択され; ここで−R12は−CH2CH2−Gであり、ここで各Gは、独立して、−Cl、 −Br、−I、−O−S(=O)2−CH3、−O−S(=O)2−CH2−C6H5 または−O−S(=O)2−C6H4−CH3であり; そしてここでR13は、独立して、−C1-8アルキル、−C1-8ヘテロアルキル、 −アリール、−ヘテロアリール、−C1-3アルキル−アリール−、−C1-3ヘテロ アルキル−アリール、−C1-3アルキル−ヘテロアリール、−C1-3ヘテロアルキ ル−ヘテロアリール、−アリール−C1-3アルキル、−アリール−C1-3ヘテロア ルキル、−ヘテロアリール−C1-3アルキル、−ヘテロアリール−C1-3ヘテロア ルキル、−C1-3アルキル−アリール−C1-3アルキル、−C1-3ヘテロアルキル −アリール−C1-3アルキル、−C1-3アルキル−ヘテロアリール−C1-3アルキ ル、−C1-3アルキル−アリール−C1-3ヘテロアルキル、−C1-3ヘテロアルキ ル−ヘテロアリール−C1-3アルキル、−C1-3ヘテロアルキル−アリール−C1- 3 ヘテロアルキル、−C1-3アルキル−ヘテロアリール−C1-3ヘテロアルキルま たは−C1-3ヘテロアルキル−ヘテロアリール−C1-3ヘテロアルキルである。 8.以下の式を有する化合物: およびその全ての塩。 9.以下の式を有する化合物: およびその全ての塩。 10.以下の式を有する化合物:およびその全ての塩。 11.以下の式を有する化合物: およびその全ての塩。 12.以下の式を有する化合物: およびその全ての塩。 13.以下の式を有する化合物: およびその全ての塩。 14.以下の式を有する化合物: およびその全ての塩。 15.以下の式を有する化合物: およびその全ての塩。 16.物質中の病原体を不活化するための方法であって、該物質へ請求項1に 記載の化合物を添加する工程;および該物質をインキュベートする工程を包含す る、方法。 17.前記化合物が1μMと500μMとの間の濃度を有する溶液を形成する ために前記物質へ添加される、請求項16に記載の方法。 18.前記物質が生物学的な物質である、請求項16に記載の方法。 19.請求項18に記載の方法であって、ここで前記生物学的な物質が以下か らなる群から選択される組成物を含む、方法:血液、血液製剤、血漿、血小板製 剤、赤血球、濃縮赤血球、血清、汗、脳脊髄液、唾液、尿、便、精液、乳、組織 試料、均質化組織試料、細胞培養培地、細胞培養物、ウイルス培養物および生存 している生物由来の物質を配合した培養物。 20.前記物質が血液製剤を含む、請求項18に記載の方法。 21.前記物質が赤血球を含む、請求項18に記載の方法。 22.請求項16に記載の方法であって、ここで該方法が、少なくとも約2ロ グ(2 log of)の前記物質中の病原体を不活性にするための有効量の前記化合物を 前記物質へ添加する工程を包含する、方法。 23.インキュベーション時間が少なくとも約1〜48時間である、請求項1 6に記載の方法。 24.請求項6に記載の化合物を製造する方法であって、ここで該方法がアミ ノエステルと9−置換アクリジンとを反応させてN−(9−アクリジニル)アミ ノエステルを提供する工程を包含する、方法。 25.前記アミノエステルがω−アミノアルカン酸エステルである、請求項2 4に記載の方法。 26.前記アミノエステルがβ−アラニン誘導体である、請求項24に記載の 方法。 27.前記アミノエステルが保護されたジオールを含む、請求項24に記載の 方法。 28.請求項27に記載の方法であって、前記保護されたジオール置換基を脱 保護して、ジオール置換基を含むN−(9−アクリジニル)アミノエステルを形 成する工程をさらに包含する、方法。 29.前記アミノエステルが保護されたビス(ヒドロキシアルキル)アミンを 含む、請求項24に記載の方法。 30.前記9−置換アクリジンが9−メトキシアクリジンである、請求項24 に記載の方法。 31.前記9−置換アクリジンが9−クロロアクリジンである、請求項24に 記載の方法。 32.請求項24に記載の方法であって、前記N−(9−アクリジニル)アミ ノエステルをジオール置換基を含むN−(9−アクリジニル)アミノエステルへ 転化する工程をさらに包含する、方法。 33.請求項32に記載の方法であって、ここで前記N−(9−アクリジニル )アミノエステルをジオール置換基を含むN−(9−アクリジニル)アミノエス テルへ転化する工程が、エステル交換反応を含む、方法。 34.請求項32に記載の方法であって、ここで前記方法がジオール置換基の 水酸基をクロロ基で置換する工程をさらに包含する、方法。 35.請求項7に記載の化合物を製造する方法であって、ここで該方法が以下 の工程を包含する、方法: a)ソラレンアセテートをエステル交換して、アミノアルキルソラレンアセ テートを提供する工程;および、 b)該アミノアルキルソラレンアセテートを(クロロアルキル)−アミノア ルキルソラレンアセテートへ転化する工程。 36.前記ソラレンアセテートがメチル置換ソラレンアセテートである、請求 項35に記載の方法。 37.前記ソラレンアセテートが4’−ソラレンアセテートである、請求項3 5に記載の方法。 38.前記アミノアルキルソラレンアセテートがアミノエチルソラレンアセテ ートである、請求項35に記載の方法。 39.前記アミノアルキルソラレンアセテートの転化が、水酸基を塩化物基へ 転化する反応を含む、請求項35に記載の方法。 40.以下を含む化合物であって: 核酸結合部分; 核酸との共有結合の形成が可能な、エフェクター部分;および 該核酸部分と該エフェクター部分とを共有連結している脆いリンカー; ここで、該物質をその意図した目的に不適切にしない条件下で、もはや該核酸 結合部分およびエフェクター部分が共有連結しないように、該脆いリンカーが分 解する、化合物。 41.前記核酸結合部分が、アクリジン、アクリジン誘導体、ソラニン、イソ ソラニンおよびソラニン誘導体からなる群より選択される、請求項40に記載の 化合物。 42.請求項40に記載の化合物であって、ここで前記脆いリンカーが、順方 向エステル、逆方向エステル、順方向アミド、逆方向アミド、順方向チオエステ ル、逆方向チオエステル、順方向および逆方向チオノエステル、順方向および逆 方向ジチオ酸、スルフェート、順方向および逆方向スルホネート、ホスフェート 、および順方向および逆方向ホスホネートの基からなる群から選択される官能性 単位から構成される、化合物。 43.エフェクター基がアルキル化試薬である官能性単位を含む、請求項40 に記載の化合物。 44.請求項40に記載の化合物であって、ここで前記エフェクター基が、マ スタード基、マスタード基等価物、エポキシド、アルデヒドおよびホルムアルデ ヒドシントンからなる群より選択される官能性単位を含む、化合物。
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WO1998030545A1 (en) * | 1997-01-06 | 1998-07-16 | Cerus Corporation | Frangible compounds for pathogen inactivation |
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JP2006521376A (ja) * | 2003-02-06 | 2006-09-21 | シーラス コーポレイション | 改変された自由生活微生物、ワクチン組成物、およびそれらの使用方法 |
JP2007131639A (ja) * | 2003-02-06 | 2007-05-31 | Cerus Corp | 改変された自由生活微生物、ワクチン組成物、およびそれらの使用方法 |
JP4839209B2 (ja) * | 2003-02-06 | 2011-12-21 | アンザ セラピューティクス,インコーポレイテッド | 改変された自由生活微生物、ワクチン組成物、およびそれらの使用方法 |
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ATE243198T1 (de) | 2003-07-15 |
EP1021414A1 (en) | 2000-07-26 |
AU5821798A (en) | 1998-08-03 |
JP4551502B2 (ja) | 2010-09-29 |
CA2276532C (en) | 2008-06-17 |
AU744089C (en) | 2003-07-31 |
JP5244083B2 (ja) | 2013-07-24 |
CN101676268B (zh) | 2013-09-25 |
CN101676268A (zh) | 2010-03-24 |
HK1026702A1 (en) | 2000-12-22 |
ES2196530T3 (es) | 2003-12-16 |
JP2010095527A (ja) | 2010-04-30 |
HK1188441A1 (en) | 2014-05-02 |
AU744089B2 (en) | 2002-02-14 |
EP1021414B1 (en) | 2003-06-18 |
CN1248245A (zh) | 2000-03-22 |
DE69815703D1 (de) | 2003-07-24 |
CA2276532A1 (en) | 1998-07-16 |
CN1248245B (zh) | 2012-07-04 |
WO1998030545A1 (en) | 1998-07-16 |
DE69815703T2 (de) | 2004-06-03 |
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