JP2003523927A - ジカチオンジベンゾフランおよびジベンゾチオフェン化合物並びにその使用法 - Google Patents
ジカチオンジベンゾフランおよびジベンゾチオフェン化合物並びにその使用法Info
- Publication number
- JP2003523927A JP2003523927A JP2000566263A JP2000566263A JP2003523927A JP 2003523927 A JP2003523927 A JP 2003523927A JP 2000566263 A JP2000566263 A JP 2000566263A JP 2000566263 A JP2000566263 A JP 2000566263A JP 2003523927 A JP2003523927 A JP 2003523927A
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- pharmaceutically acceptable
- acceptable salt
- alkylaryl
- aryl
- 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.)
- Pending
Links
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 title abstract description 19
- IYYZUPMFVPLQIF-ALWQSETLSA-N dibenzothiophene Chemical class C1=CC=CC=2[34S]C3=C(C=21)C=CC=C3 IYYZUPMFVPLQIF-ALWQSETLSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 238000000034 method Methods 0.000 claims abstract description 81
- -1 dibenzofuran compound Chemical class 0.000 claims abstract description 44
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 claims abstract description 33
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 claims abstract description 33
- 201000000317 pneumocystosis Diseases 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims description 101
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 64
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 35
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 33
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 30
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 22
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 17
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 10
- 125000005001 aminoaryl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 5
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 5
- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene sulfoxide Natural products C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 abstract description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 91
- 239000000243 solution Substances 0.000 description 53
- 229910052757 nitrogen Inorganic materials 0.000 description 52
- 239000007787 solid Substances 0.000 description 40
- 239000000203 mixture Substances 0.000 description 38
- 238000004458 analytical method Methods 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 238000004128 high performance liquid chromatography Methods 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 25
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 229910052799 carbon Inorganic materials 0.000 description 24
- 229910052801 chlorine Inorganic materials 0.000 description 24
- 239000000725 suspension Substances 0.000 description 24
- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 17
- 239000012458 free base Substances 0.000 description 17
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 11
- 229960004448 pentamidine Drugs 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 10
- YBVNFKZSMZGRAD-UHFFFAOYSA-N pentamidine isethionate Chemical compound OCCS(O)(=O)=O.OCCS(O)(=O)=O.C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 YBVNFKZSMZGRAD-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000003389 potentiating effect Effects 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 150000003457 sulfones Chemical class 0.000 description 9
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000004568 DNA-binding Effects 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 244000309466 calf Species 0.000 description 6
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 6
- LHRXOUZBYQFVMV-UHFFFAOYSA-N dibenzofuran-2,8-dicarbonitrile Chemical compound C1=C(C#N)C=C2C3=CC(C#N)=CC=C3OC2=C1 LHRXOUZBYQFVMV-UHFFFAOYSA-N 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 210000001541 thymus gland Anatomy 0.000 description 6
- 206010035664 Pneumonia Diseases 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 150000001716 carbazoles Chemical class 0.000 description 5
- VPEXKVZOURGOKV-UHFFFAOYSA-N dibenzofuran-3,7-dicarbonitrile Chemical compound N#CC1=CC=C2C3=CC=C(C#N)C=C3OC2=C1 VPEXKVZOURGOKV-UHFFFAOYSA-N 0.000 description 5
- IQFOWQNSBODWQI-UHFFFAOYSA-N dibenzothiophene-2,8-dicarbonitrile Chemical compound C1=C(C#N)C=C2C3=CC(C#N)=CC=C3SC2=C1 IQFOWQNSBODWQI-UHFFFAOYSA-N 0.000 description 5
- NZGXURMFODWVKR-UHFFFAOYSA-N dibenzothiophene-3,7-dicarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=CC=C2C3=CC=C(C(=N)N)C=C3SC2=C1 NZGXURMFODWVKR-UHFFFAOYSA-N 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010061598 Immunodeficiency Diseases 0.000 description 4
- 238000003482 Pinner synthesis reaction Methods 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 150000004826 dibenzofurans Chemical class 0.000 description 4
- BNNWPSAGYXTUAC-UHFFFAOYSA-N dibenzothiophene-3,7-dicarbonitrile Chemical compound N#CC1=CC=C2C3=CC=C(C#N)C=C3SC2=C1 BNNWPSAGYXTUAC-UHFFFAOYSA-N 0.000 description 4
- 125000000950 dibromo group Chemical group Br* 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 150000002463 imidates Chemical class 0.000 description 4
- 238000004452 microanalysis Methods 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 150000003462 sulfoxides Chemical class 0.000 description 4
- CHDZNTSBYBEBTQ-UHFFFAOYSA-N 1-[8-(4,5-dihydroimidazol-1-yl)dibenzothiophen-2-yl]-4,5-dihydroimidazole;dihydrochloride Chemical compound Cl.Cl.C1=NCCN1C1=CC=C(SC=2C3=CC(=CC=2)N2C=NCC2)C3=C1 CHDZNTSBYBEBTQ-UHFFFAOYSA-N 0.000 description 3
- GBCYJXFJGQKMPY-UHFFFAOYSA-N 3,7-dibromodibenzofuran Chemical compound BrC1=CC=C2C3=CC=C(Br)C=C3OC2=C1 GBCYJXFJGQKMPY-UHFFFAOYSA-N 0.000 description 3
- KMNBVODPWIFUSS-UHFFFAOYSA-N 3,7-dibromodibenzothiophene Chemical compound BrC1=CC=C2C3=CC=C(Br)C=C3SC2=C1 KMNBVODPWIFUSS-UHFFFAOYSA-N 0.000 description 3
- DSDSVHLSVVQUSM-UHFFFAOYSA-N 5-bromo-2-(4-bromo-2-methoxyphenyl)aniline Chemical group COC1=CC(Br)=CC=C1C1=CC=C(Br)C=C1N DSDSVHLSVVQUSM-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001409 amidines Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000031709 bromination Effects 0.000 description 3
- 238000005893 bromination reaction Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- HPOKESDSMZRZLC-UHFFFAOYSA-N propan-2-one;hydrochloride Chemical compound Cl.CC(C)=O HPOKESDSMZRZLC-UHFFFAOYSA-N 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
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- 239000002904 solvent Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- RRCIJLBMQJGTJN-UHFFFAOYSA-N (E)-[amino-[7-[(E)-amino(hydroxyazaniumylidene)methyl]dibenzothiophen-3-yl]methylidene]-hydroxyazanium dichloride Chemical compound Cl.Cl.ONC(=N)C1=CC=C2C3=CC=C(C(=N)NO)C=C3SC2=C1 RRCIJLBMQJGTJN-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- HJVIIKACDCRZHM-UHFFFAOYSA-N 1-n',7-n'-di(propan-2-yl)-9h-carbazole-1,7-dicarboximidamide;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C3=CC=C(C(=N)NC(C)C)C=C3NC2=C1C(=N)NC(C)C HJVIIKACDCRZHM-UHFFFAOYSA-N 0.000 description 2
- VLBCMZRPFFBRCK-UHFFFAOYSA-N 1-n',7-n'-dihydroxy-9h-carbazole-1,7-dicarboximidamide Chemical compound C1=CC=C2C3=CC=C(C(=N)NO)C=C3NC2=C1C(=N)NO VLBCMZRPFFBRCK-UHFFFAOYSA-N 0.000 description 2
- LEEHEYFEAYBKDK-UHFFFAOYSA-N 1-n',7-n'-dihydroxy-9h-carbazole-1,7-dicarboximidamide;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C3=CC=C(C(=N)NO)C=C3NC2=C1C(=N)NO LEEHEYFEAYBKDK-UHFFFAOYSA-N 0.000 description 2
- VHBIVEIYVGLLGN-UHFFFAOYSA-N 2,8-bis(4,5-dihydroimidazol-1-yl)dibenzothiophene 5,5-dioxide;dihydrochloride Chemical compound Cl.Cl.C=1C=C2S(=O)(=O)C3=CC=C(N4C=NCC4)C=C3C2=CC=1N1CCN=C1 VHBIVEIYVGLLGN-UHFFFAOYSA-N 0.000 description 2
- UFCZRCPQBWIXTR-UHFFFAOYSA-N 2,8-dibromodibenzofuran Chemical compound C1=C(Br)C=C2C3=CC(Br)=CC=C3OC2=C1 UFCZRCPQBWIXTR-UHFFFAOYSA-N 0.000 description 2
- REUCYFQYHWKXPH-UHFFFAOYSA-N 4-bromo-1-(4-bromo-2-nitrophenyl)-2-nitrobenzene Chemical group [O-][N+](=O)C1=CC(Br)=CC=C1C1=CC=C(Br)C=C1[N+]([O-])=O REUCYFQYHWKXPH-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 241001214254 Pentanemus quinquarius Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000003473 anti-pneumocystis Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- NCMHKCKGHRPLCM-UHFFFAOYSA-N caesium(1+) Chemical compound [Cs+] NCMHKCKGHRPLCM-UHFFFAOYSA-N 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- 239000011928 denatured alcohol Substances 0.000 description 2
- NGDPCAMPVQYGCW-UHFFFAOYSA-N dibenzothiophene 5-oxide Chemical compound C1=CC=C2S(=O)C3=CC=CC=C3C2=C1 NGDPCAMPVQYGCW-UHFFFAOYSA-N 0.000 description 2
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- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- OIIWPAYIXDCDNL-UHFFFAOYSA-M sodium 3-(trimethylsilyl)propionate Chemical compound [Na+].C[Si](C)(C)CCC([O-])=O OIIWPAYIXDCDNL-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000000176 sodium gluconate Substances 0.000 description 1
- 235000012207 sodium gluconate Nutrition 0.000 description 1
- 229940005574 sodium gluconate Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- 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
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/08—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis for Pneumocystis carinii
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/76—Dibenzothiophenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9727398P | 1998-08-20 | 1998-08-20 | |
| US60/097,273 | 1998-08-20 | ||
| PCT/US1999/014313 WO2000010990A2 (en) | 1998-08-20 | 1999-06-24 | Dicationic dibenzofuran and dibenzothiophene compounds and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003523927A true JP2003523927A (ja) | 2003-08-12 |
| JP2003523927A5 JP2003523927A5 (enExample) | 2006-07-13 |
Family
ID=22262567
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000566263A Pending JP2003523927A (ja) | 1998-08-20 | 1999-06-24 | ジカチオンジベンゾフランおよびジベンゾチオフェン化合物並びにその使用法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6172104B1 (enExample) |
| EP (1) | EP1105381B1 (enExample) |
| JP (1) | JP2003523927A (enExample) |
| AT (1) | ATE239003T1 (enExample) |
| AU (1) | AU758563B2 (enExample) |
| CA (1) | CA2340912C (enExample) |
| DE (1) | DE69907476T2 (enExample) |
| ES (1) | ES2198139T3 (enExample) |
| WO (1) | WO2000010990A2 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2784678B1 (fr) * | 1998-09-23 | 2002-11-29 | Sod Conseils Rech Applic | Nouveaux derives de n-(iminomethyl)amines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
| US6569853B1 (en) * | 2000-11-06 | 2003-05-27 | Combinatorx, Incorporated | Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders |
| GB2380192B8 (en) * | 2001-02-09 | 2005-09-14 | Sumitomo Chemical Co | Phenylacetylene compounds liquid crystal compositions polymers optically anisotropic products & optical & liquid crystal elements derived therefrom |
| JP2002255960A (ja) * | 2001-02-27 | 2002-09-11 | Sumitomo Chem Co Ltd | ジベンゾチオフェン化合物、中間体およびその製造方法 |
| JP2005505508A (ja) * | 2001-06-13 | 2005-02-24 | ジーンソフト ファーマシューティカルズ インコーポレイテッド | 抗感染活性を有するベンゾチオフェン化合物 |
| BR0212078A (pt) * | 2001-08-31 | 2004-09-28 | Neurochem Int Ltd | Método de tratar ou prevenir uma doença relacionada com amilóide em um paciente, composição farmacêutica, composto quìmico, e, uso de um composto |
| SG124249A1 (en) * | 2001-12-07 | 2006-08-30 | Sumitomo Chemical Co | New polymer and polymer light-emitting device using the same |
| JP4957669B2 (ja) * | 2002-03-15 | 2012-06-20 | 住友化学株式会社 | 高分子化合物およびそれを用いた高分子発光素子 |
| AU2003258022A1 (en) | 2002-08-02 | 2004-02-23 | Genesoft Pharmaceuticals, Inc. | Biaryl compounds having anti-infective activity |
| US7265129B2 (en) * | 2002-10-25 | 2007-09-04 | Genesoft Pharmaceuticals, Inc. | Anti-infective biaryl compounds |
| EP1587529A4 (en) | 2002-12-10 | 2009-08-12 | Oscient Pharmaceuticals Corp | ANTIBACTERIAL COMPOUNDS WITH (PYROCARBOXAMIDE) - (BENZAMID) - (IMIDAZOLE CARBOXAMIDE) MOTIVE |
| US20050054708A1 (en) * | 2003-07-28 | 2005-03-10 | Nichols Matthew James | Combinations of drugs for the treatment of neoplasms |
| US20050080075A1 (en) * | 2003-08-25 | 2005-04-14 | Nichols M. James | Formulations, conjugates, and combinations of drugs for the treatment of neoplasms |
| US20050158320A1 (en) * | 2003-11-12 | 2005-07-21 | Nichols M. J. | Combinations for the treatment of proliferative diseases |
| US20050100508A1 (en) * | 2003-11-12 | 2005-05-12 | Nichols M. J. | Methods for identifying drug combinations for the treatment of proliferative diseases |
| WO2005051296A2 (en) * | 2003-11-24 | 2005-06-09 | University Of North Carolina At Chapel Hill | Fused ring dicationic anti-protozoan agents and their prodrugs |
| US7262223B2 (en) * | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
| US7365193B2 (en) | 2004-02-04 | 2008-04-29 | Abbott Laboratories | Amino-substituted tricyclic derivatives and methods of use |
| US7994225B2 (en) * | 2004-03-17 | 2011-08-09 | Rempex Pharmaceuticals, Inc. | Bacterial efflux pump inhibitors for the treatment of ophthalmic and otic infections |
| CA2559208A1 (en) * | 2004-03-17 | 2005-09-29 | Mpex Pharmaceuticals, Inc. | Use and administration of bacterial efflux pump inhibitors |
| DE102004031656A1 (de) * | 2004-06-30 | 2006-01-19 | Merck Patent Gmbh | Tetrahydrochinoline |
| GB0619325D0 (en) * | 2006-09-30 | 2006-11-08 | Univ Strathclyde | New compounds |
| US20090092574A1 (en) | 2006-12-29 | 2009-04-09 | Scott Richard W | Ophthalmic And Otic Compositions Of Facially Amphiphilic Polymers And Oligomers And Uses Thereof |
| DE102007013854A1 (de) | 2007-03-20 | 2008-09-25 | Merck Patent Gmbh | Tetrahydrochinoline |
| DE102007013855A1 (de) | 2007-03-20 | 2008-09-25 | Merck Patent Gmbh | Substituierte Tetrahydrochinoline |
| DE102007013856A1 (de) | 2007-03-20 | 2008-09-25 | Merck Patent Gmbh | Substituierte Tetrahydropyrrolochinoline |
| CA2732572A1 (en) * | 2008-07-28 | 2010-02-04 | Polymedix, Inc. | Anti-malarial compounds |
| US8278309B2 (en) | 2008-10-27 | 2012-10-02 | Polymedix, Inc. | Synthetic mimetics of host defense and uses thereof |
| BR112012016570A2 (pt) * | 2010-01-07 | 2016-04-05 | Polymedix Inc | composto, composição farmacêutica, método para antagonizar a heparina não fracionada, heparina de peso molecular baixo, ou derivado de heparina /heparina de peso molecular baixo, e, uso do composto |
| TWI520951B (zh) | 2011-05-16 | 2016-02-11 | 塞爾西優蒂克斯公司 | 用於治療粘膜炎的化合物 |
| US11771694B2 (en) | 2020-06-05 | 2023-10-03 | Innovation Pharmaceuticals Inc. | Arylamide compounds for treatment and prevention of viral infections |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040114A1 (en) * | 1995-06-07 | 1996-12-19 | The University Of North Carolina At Chapel Hill | Methods of inhibiting pneumocystis carinii pneumonia and compounds useful therefor |
| WO1997017949A1 (en) * | 1995-11-16 | 1997-05-22 | The University Of North Carolina At Chapel Hill | Benzamidoxime prodrugs as antipneumocystic agents |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2500734A (en) * | 1946-06-13 | 1950-03-14 | Gen Electric | Process of preparing 2-ethyldibenzofuran |
| GB932813A (en) * | 1960-12-01 | 1963-07-31 | Monsanto Chemicals | New heterocyclic chemical compounds |
| GB951797A (en) * | 1960-12-20 | 1964-03-11 | Monsanto Chemicals | Heterocyclic compounds |
| US4362883A (en) * | 1981-10-28 | 1982-12-07 | The Halcon Sd Group, Inc. | Preparation of dibenzofuran |
| AU626033B2 (en) | 1988-10-25 | 1992-07-23 | Government Of The United States Of America, As Represented By The Secretary Of The Army, The | Methods for the treatment and prophylaxis of pneumocystis carinii pneumonia and other diseases and compounds and formulations for use in said methods |
| IL115875A (en) | 1994-11-14 | 2000-12-06 | Univ Georgia State Res Found | Methods of inhibiting pneumocystis carinii pneumonia giardia lamblia and cryptosporidium parvum in an animal subject and compounds useful therefor |
| WO1996040117A1 (en) | 1995-06-07 | 1996-12-19 | The University Of North Carolina At Chapel Hill | Methods of treating microbial infections |
-
1999
- 1999-06-24 JP JP2000566263A patent/JP2003523927A/ja active Pending
- 1999-06-24 AT AT99930662T patent/ATE239003T1/de not_active IP Right Cessation
- 1999-06-24 ES ES99930662T patent/ES2198139T3/es not_active Expired - Lifetime
- 1999-06-24 DE DE69907476T patent/DE69907476T2/de not_active Expired - Fee Related
- 1999-06-24 US US09/344,143 patent/US6172104B1/en not_active Expired - Lifetime
- 1999-06-24 CA CA002340912A patent/CA2340912C/en not_active Expired - Fee Related
- 1999-06-24 AU AU47152/99A patent/AU758563B2/en not_active Ceased
- 1999-06-24 WO PCT/US1999/014313 patent/WO2000010990A2/en not_active Ceased
- 1999-06-24 EP EP99930662A patent/EP1105381B1/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996040114A1 (en) * | 1995-06-07 | 1996-12-19 | The University Of North Carolina At Chapel Hill | Methods of inhibiting pneumocystis carinii pneumonia and compounds useful therefor |
| WO1997017949A1 (en) * | 1995-11-16 | 1997-05-22 | The University Of North Carolina At Chapel Hill | Benzamidoxime prodrugs as antipneumocystic agents |
Also Published As
| Publication number | Publication date |
|---|---|
| DE69907476D1 (de) | 2003-06-05 |
| AU758563B2 (en) | 2003-03-27 |
| ES2198139T3 (es) | 2004-01-16 |
| EP1105381B1 (en) | 2003-05-02 |
| AU4715299A (en) | 2000-03-14 |
| WO2000010990A3 (en) | 2003-04-17 |
| US6172104B1 (en) | 2001-01-09 |
| WO2000010990A2 (en) | 2000-03-02 |
| ATE239003T1 (de) | 2003-05-15 |
| CA2340912C (en) | 2008-11-18 |
| CA2340912A1 (en) | 2000-03-02 |
| DE69907476T2 (de) | 2004-04-15 |
| EP1105381A1 (en) | 2001-06-13 |
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