JPH11507036A - ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法 - Google Patents

ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法

Info

Publication number: JPH11507036A
Authority: JP; Japan
Prior art keywords: bis; benzimidazolyl; structural formula; following structural; lower alkyl
Prior art date: 1995-06-07
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.): Ceased

Application number

JP9500868A

Other languages

English (en)

Japanese (ja)

Other versions

JPH11507036A5 (2

Inventor

ダイクストラ，クリスティン・シー

パーフェクト，ジョン・アール

ボイキン，デイヴィッド・ダブリュー

ウィルソン，ダブリュー・デイヴィッド

ティドウェル，リチャード・アール

Original Assignee

ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル

デューク・ユニヴァーシティ

ジョージア・ステイト・ユニヴァーシティ・リサーチ・ファンデイション，インコーポレイテッド

Priority date (The priority date 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 date listed.)

1995-06-07

Filing date

1996-06-03

Publication date

1999-06-22

1996-06-03 Application filed by ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル, デューク・ユニヴァーシティ, ジョージア・ステイト・ユニヴァーシティ・リサーチ・ファンデイション，インコーポレイテッド filed Critical ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル

1999-06-22 Publication of JPH11507036A publication Critical patent/JPH11507036A/ja

2004-07-22 Publication of JPH11507036A5 publication Critical patent/JPH11507036A5/ja

Status Ceased legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 90
208000015181 infectious disease Diseases 0.000 title description 7
208000035473 Communicable disease Diseases 0.000 title description 5
238000011282 treatment Methods 0.000 claims abstract description 28
241000222122 Candida albicans Species 0.000 claims abstract description 11
229940095731 candida albicans Drugs 0.000 claims abstract description 9
150000001875 compounds Chemical class 0.000 claims description 92
150000003839 salts Chemical class 0.000 claims description 50
125000000217 alkyl group Chemical group 0.000 claims description 47
-1 2-imidazolinyl Chemical group 0.000 claims description 38
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 34
125000004103 aminoalkyl group Chemical group 0.000 claims description 17
206010028980 Neoplasm Diseases 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 15
201000007336 Cryptococcosis Diseases 0.000 claims description 13
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
241000221204 Cryptococcus neoformans Species 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 10
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 9
125000002877 alkyl aryl group Chemical group 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 6
WQQBZMQGGMYWOT-UHFFFAOYSA-N 2-[5-(6-carbamimidoyl-1h-benzimidazol-2-yl)-1h-pyrrol-2-yl]-3h-benzimidazole-5-carboximidamide Chemical compound C1=C(C(N)=N)C=C2NC(C3=CC=C(N3)C3=NC4=CC=C(C=C4N3)C(=N)N)=NC2=C1 WQQBZMQGGMYWOT-UHFFFAOYSA-N 0.000 claims description 5
FZFQYUOWNRDPNY-UHFFFAOYSA-N 2-[5-(6-carbamimidoyl-1h-benzimidazol-2-yl)furan-2-yl]-3h-benzimidazole-5-carboximidamide Chemical compound C1=C(C(N)=N)C=C2NC(C3=CC=C(O3)C3=NC4=CC=C(C=C4N3)C(=N)N)=NC2=C1 FZFQYUOWNRDPNY-UHFFFAOYSA-N 0.000 claims description 5
XEHGMWQTKPXNEZ-UHFFFAOYSA-N 2-[6-(6-carbamimidoyl-1h-benzimidazole-2-carbonyl)pyridine-2-carbonyl]-3h-benzimidazole-5-carboximidamide Chemical compound C1=C(C(N)=N)C=C2NC(C(=O)C=3C=CC=C(N=3)C(=O)C3=NC4=CC=C(C=C4N3)C(=N)N)=NC2=C1 XEHGMWQTKPXNEZ-UHFFFAOYSA-N 0.000 claims description 5
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 5
ADBIDLGZBNZQMZ-UHFFFAOYSA-N 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[6-[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1h-benzimidazol-2-yl]pyridin-2-yl]-1h-benzimidazole Chemical compound C1CCNC(C=2C=C3NC(=NC3=CC=2)C=2N=C(C=CC=2)C=2NC3=CC(=CC=C3N=2)C=2NCCCN=2)=N1 ADBIDLGZBNZQMZ-UHFFFAOYSA-N 0.000 claims description 4
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
239000004472 Lysine Substances 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
125000005001 aminoaryl group Chemical group 0.000 claims description 4
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
125000005429 oxyalkyl group Chemical group 0.000 claims description 4
208000032839 leukemia Diseases 0.000 claims description 2
KFBOGYGJZQZRDR-UHFFFAOYSA-N 6-(1h-imidazol-2-yl)-2-[5-[6-(1h-imidazol-2-yl)-1h-benzimidazol-2-yl]-1-methylpyrrol-2-yl]-1h-benzimidazole Chemical compound CN1C(C=2NC3=CC(=CC=C3N=2)C=2NC=CN=2)=CC=C1C(NC1=C2)=NC1=CC=C2C1=NC=CN1 KFBOGYGJZQZRDR-UHFFFAOYSA-N 0.000 claims 2
230000003449 preventive effect Effects 0.000 claims 1
241001337994 Cryptococcus <scale insect> Species 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 abstract description 2
125000002091 cationic group Chemical group 0.000 abstract 1
239000007787 solid Substances 0.000 description 25
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
229910052757 nitrogen Inorganic materials 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
239000000203 mixture Substances 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
238000002360 preparation method Methods 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
239000002502 liposome Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
239000002245 particle Substances 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
239000007788 liquid Substances 0.000 description 7
208000030507 AIDS Diseases 0.000 description 6
206010017533 Fungal infection Diseases 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
208000031888 Mycoses Diseases 0.000 description 6
201000011510 cancer Diseases 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000000243 solution Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
206010061598 Immunodeficiency Diseases 0.000 description 5
238000009472 formulation Methods 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
PXJJKVNIMAZHCB-UHFFFAOYSA-N 2,5-diformylfuran Chemical compound O=CC1=CC=C(C=O)O1 PXJJKVNIMAZHCB-UHFFFAOYSA-N 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
238000002512 chemotherapy Methods 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
238000005259 measurement Methods 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
MKVBQBLIGAFRIY-UHFFFAOYSA-N 1h-pyrrole-2,5-dicarbaldehyde Chemical compound O=CC1=CC=C(C=O)N1 MKVBQBLIGAFRIY-UHFFFAOYSA-N 0.000 description 3
YQQCEOMFCLGSTF-UHFFFAOYSA-N 3,4-diaminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C(N)=C1 YQQCEOMFCLGSTF-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
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
150000001299 aldehydes Chemical class 0.000 description 3
150000003851 azoles Chemical class 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
238000005516 engineering process Methods 0.000 description 3
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000012458 free base Substances 0.000 description 3
230000036541 health Effects 0.000 description 3
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
HMGXRGDTHQEUAO-UHFFFAOYSA-N 1-methylpyrrole-2,5-dicarbaldehyde Chemical compound CN1C(C=O)=CC=C1C=O HMGXRGDTHQEUAO-UHFFFAOYSA-N 0.000 description 2
URHAYTBLIGBVEN-UHFFFAOYSA-N 2-[1-methyl-5-[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1h-benzimidazol-2-yl]pyrrol-2-yl]-6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1h-benzimidazole Chemical compound CN1C(C=2NC3=CC(=CC=C3N=2)C=2NCCCN=2)=CC=C1C(NC1=C2)=NC1=CC=C2C1=NCCCN1 URHAYTBLIGBVEN-UHFFFAOYSA-N 0.000 description 2
UEPHLCIPPLUKCV-UHFFFAOYSA-N 3,4-diamino-n'-propan-2-ylbenzenecarboximidamide Chemical compound CC(C)NC(=N)C1=CC=C(N)C(N)=C1 UEPHLCIPPLUKCV-UHFFFAOYSA-N 0.000 description 2
XNXZZFQZGVFMAN-UHFFFAOYSA-N 4-bromo-1,2-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1[N+]([O-])=O XNXZZFQZGVFMAN-UHFFFAOYSA-N 0.000 description 2
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
239000000232 Lipid Bilayer Substances 0.000 description 2
208000001388 Opportunistic Infections Diseases 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
239000002253 acid Substances 0.000 description 2
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
229960003942 amphotericin b Drugs 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
229940121375 antifungal agent Drugs 0.000 description 2
239000003429 antifungal agent Substances 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
230000027455 binding Effects 0.000 description 2
230000010261 cell growth Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
229940125782 compound 2 Drugs 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
238000003113 dilution method Methods 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
229960004413 flucytosine Drugs 0.000 description 2
230000000855 fungicidal effect Effects 0.000 description 2
239000011521 glass Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000002054 inoculum Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
230000000813 microbial effect Effects 0.000 description 2
230000002335 preservative effect Effects 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
229940005561 1,4-benzoquinone Drugs 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 1
PCAXITAPTVOLGL-UHFFFAOYSA-N 2,3-diaminophenol Chemical class NC1=CC=CC(O)=C1N PCAXITAPTVOLGL-UHFFFAOYSA-N 0.000 description 1
ZAZIHUNVAYAPPG-UHFFFAOYSA-N 2-[5-(6-carbamimidoyl-1H-benzimidazol-2-yl)-1H-pyrrol-2-yl]-3H-benzimidazole-5-carboximidamide Chemical compound C(N)(=N)C1=CC2=C(N=C(N2)C=2NC(=CC2)C=2NC3=C(N2)C=CC(=C3)C(N)=N)C=C1.C(N)(=N)C1=CC3=C(N=C(N3)C=3NC(=CC3)C=3NC2=C(N3)C=CC(=C2)C(N)=N)C=C1 ZAZIHUNVAYAPPG-UHFFFAOYSA-N 0.000 description 1
238000010600 3H thymidine incorporation assay Methods 0.000 description 1
BVMJUFXKJJPTRF-UHFFFAOYSA-N 4-(1,2,3,4-tetrahydropyrimidin-2-yl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1NC=CCN1 BVMJUFXKJJPTRF-UHFFFAOYSA-N 0.000 description 1
QVZGXYWTAPUJRR-UHFFFAOYSA-N 4-(4,5-dihydro-1h-imidazol-2-yl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1=NCCN1 QVZGXYWTAPUJRR-UHFFFAOYSA-N 0.000 description 1
CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 description 1
SCMKFZGXSFMPLB-UHFFFAOYSA-N 5-[cyano(1,3-dihydrobenzimidazol-2-ylidene)methyl]-6-(4-methylpiperazin-1-yl)pyrazine-2,3-dicarbonitrile Chemical compound C1CN(C)CCN1C1=NC(C#N)=C(C#N)N=C1C(C#N)=C1NC2=CC=CC=C2N1 SCMKFZGXSFMPLB-UHFFFAOYSA-N 0.000 description 1
VHHKFLLLDZYYPW-UHFFFAOYSA-N 6-bromo-2-(1H-pyrrol-2-yl)-1H-benzimidazole Chemical compound BrC1=CC2=C(N=C(N2)C=2NC=CC2)C=C1 VHHKFLLLDZYYPW-UHFFFAOYSA-N 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
241000756964 Artema atlanta Species 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
CZHTXVXBAUZPEB-UHFFFAOYSA-N C(N)(=N)C1=CC2=C(N=C(N2)C(=O)C2=NC(=CC=C2)C(=O)C=2NC3=C(N2)C=CC(=C3)C(N)=N)C=C1.C(N)(=N)C1=CC3=C(N=C(N3)C(=O)C3=NC(=CC=C3)C(=O)C=3NC2=C(N3)C=CC(=C2)C(N)=N)C=C1 Chemical compound C(N)(=N)C1=CC2=C(N=C(N2)C(=O)C2=NC(=CC=C2)C(=O)C=2NC3=C(N2)C=CC(=C3)C(N)=N)C=C1.C(N)(=N)C1=CC3=C(N=C(N3)C(=O)C3=NC(=CC=C3)C(=O)C=3NC2=C(N3)C=CC(=C2)C(N)=N)C=C1 CZHTXVXBAUZPEB-UHFFFAOYSA-N 0.000 description 1
241000222120 Candida <Saccharomycetales> Species 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
241001529936 Murinae Species 0.000 description 1
241001553014 Myrsine salicina Species 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000012979 RPMI medium Substances 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
229940122803 Vinca alkaloid Drugs 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
229940022663 acetate Drugs 0.000 description 1
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
238000002827 antifungal susceptibility testing Methods 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
229960004217 benzyl alcohol Drugs 0.000 description 1
229910021538 borax Inorganic materials 0.000 description 1
238000002815 broth microdilution Methods 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
208000035269 cancer or benign tumor Diseases 0.000 description 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
ZFXTZKMYLJXJDY-UHFFFAOYSA-N copper;oxalonitrile Chemical compound [Cu].N#CC#N ZFXTZKMYLJXJDY-UHFFFAOYSA-N 0.000 description 1
238000012937 correction Methods 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
229960000975 daunorubicin Drugs 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
150000001993 dienes Chemical class 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
230000012010 growth Effects 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
230000035876 healing Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000005350 hydroxycycloalkyl group Chemical group 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
230000036039 immunity Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
208000003747 lymphoid leukemia Diseases 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
239000003595 mist Substances 0.000 description 1
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
229960001156 mitoxantrone Drugs 0.000 description 1
KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000010957 pewter Substances 0.000 description 1
229910000498 pewter Inorganic materials 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
PMWXGSWIOOVHEQ-UHFFFAOYSA-N pyridine-2,6-dicarbaldehyde Chemical compound O=CC1=CC=CC(C=O)=N1 PMWXGSWIOOVHEQ-UHFFFAOYSA-N 0.000 description 1
238000000197 pyrolysis Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000012216 screening Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 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
229940005581 sodium lactate Drugs 0.000 description 1
235000011088 sodium lactate Nutrition 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
238000001228 spectrum Methods 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
238000004114 suspension culture Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
238000002054 transplantation 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
231100000397 ulcer Toxicity 0.000 description 1
230000035899 viability Effects 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

JP9500868A 1995-06-07 1996-06-03 ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法 Ceased JPH11507036A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US08/472,996 US5643935A (en)	1995-06-07	1995-06-07	Method of combatting infectious diseases using dicationic bis-benzimidazoles
US08/472,996		1995-06-07
PCT/US1996/008084 WO1996040145A1 (en)	1995-06-07	1996-06-03	Methods of combatting infectious diseases using dicationic bis-benzimidazoles

Publications (2)

Publication Number	Publication Date
JPH11507036A true JPH11507036A (ja)	1999-06-22
JPH11507036A5 JPH11507036A5 (2)	2004-07-22

Family

ID=23877744

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP9500868A Ceased JPH11507036A (ja)	1995-06-07	1996-06-03	ジカチオン性ビス−ベンズイミダゾール類を用いた感染病治療方法

Country Status (9)

Country	Link
US (11)	US5643935A (2)
EP (1)	EP0831832B1 (2)
JP (1)	JPH11507036A (2)
AT (1)	ATE256464T1 (2)
AU (1)	AU705261B2 (2)
CA (1)	CA2223912A1 (2)
DE (1)	DE69631134T2 (2)
ES (1)	ES2213775T3 (2)
WO (1)	WO1996040145A1 (2)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5770617A (en) *	1996-03-20	1998-06-23	Rutgers, The State University Of New Jersey	Terbenzimidazoles useful as antifungal agents
US5935982A (en) *	1997-02-28	1999-08-10	The University Of North Carolina At Chapel Hill	Methods of treating retroviral infection and compounds useful therefor
US6635668B1 (en) *	1998-07-22	2003-10-21	The University Of North Carolina At Chapel Hill	Imidazoline receptor binding compounds
JP2002524503A (ja)	1998-09-17	2002-08-06	ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル	二陽イオン分子の抗真菌活性
EP1685836A3 (en) *	1998-09-17	2007-05-09	University Of North Carolina At Chapel Hill	Antifungal activity of dicationic molecules
DE60042921D1 (de) *	1999-03-29	2009-10-22	Shire Canada Inc	Verwendung von cytidinderivaten zur behandlung von leukämie
DK1231910T3 (da) *	1999-11-16	2009-08-31	Oncozyme Pharma Inc	Pentamidin til behandling af cancer
US7115665B1 (en)	2000-11-16	2006-10-03	Onocozyme Pharma, Inc.	Inhibitors of endo-exonuclease activity for treating cancer
US7156809B2 (en)	1999-12-17	2007-01-02	Q-Tec Systems Llc	Method and apparatus for health and disease management combining patient data monitoring with wireless internet connectivity
US6677377B2 (en) *	2000-06-21	2004-01-13	Georgetown University School Of Medicine	Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions
US6569853B1 (en) *	2000-11-06	2003-05-27	Combinatorx, Incorporated	Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders
US6706754B2 (en) *	2000-11-06	2004-03-16	The United States Of America As Represented By The Secretary Of The Army	Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis
US20040006092A1 (en) *	2001-08-31	2004-01-08	Neurochem, Inc.	Amidine derivatives for treating amyloidosis
US6951880B2 (en)	2002-05-16	2005-10-04	Genelabs Technologies, Inc.	Aryl and heteroaryl compounds as antibacterial and antifungal agents
AU2003245442B2 (en) *	2002-06-13	2009-02-05	Vertex Pharmaceuticals Incorporated	2-ureido-6-heteroaryl-3h-benzoimidazole-4-carboxylic acid derivatives and related compounds as gyrase and/or topoisomerase IV inhibitors for the treatment of bacterial infections
US7569591B2 (en) *	2003-01-31	2009-08-04	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7618974B2 (en) *	2003-01-31	2009-11-17	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US8193352B2 (en) *	2003-01-31	2012-06-05	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7582641B2 (en) *	2003-01-31	2009-09-01	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
AR042956A1 (es) *	2003-01-31	2005-07-13	Vertex Pharma	Inhibidores de girasa y usos de los mismos
US8404852B2 (en)	2003-01-31	2013-03-26	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
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
US7262223B2 (en) *	2004-01-23	2007-08-28	Neurochem (International) Limited	Amidine derivatives for treating amyloidosis
US7967605B2 (en)	2004-03-16	2011-06-28	Guidance Endodontics, Llc	Endodontic files and obturator devices and methods of manufacturing same
AU2005233632A1 (en)	2004-04-13	2005-10-27	Icagen, Inc.	Polycyclic pyridines as potassium ion channel modulators
DE102004031656A1 (de) *	2004-06-30	2006-01-19	Merck Patent Gmbh	Tetrahydrochinoline
US7817792B2 (en) *	2006-05-04	2010-10-19	Microsoft Corporation	Hyperlink-based softphone call and management
DE102007013854A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Tetrahydrochinoline
DE102007013856A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydropyrrolochinoline
DE102007013855A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydrochinoline
EP2194981B1 (en) *	2007-10-05	2011-11-23	Université de Mons-Hainaut	Bisbenzimidazoles as antimalarial agents
WO2010132684A2 (en) *	2009-05-13	2010-11-18	University Of Virginia Patent Foundation	Inhibitors of inv(16) leukemia
JP6085829B2 (ja)	2011-01-14	2017-03-01	スペロトリネム，インコーポレイテッド	ピリミジンジャイレースおよびトポイソメラーゼｉｖ阻害剤
MX341342B (es)	2011-01-14	2016-08-17	Vertex Pharma	Formas solidas del inhibidor de girasa (r)-1-etil-3-[6-fluoro-5-[2 -(1-hidroxi-1-metil-etil) pirimidin-5-il]-7-(tetrahidrofuran-2-il) -1h-benzimidazol-2-il]urea.
US8481552B2 (en)	2011-01-14	2013-07-09	Vertex Pharmaceuticals Incorporated	Solid forms of gyrase inhibitor (R)-1-ethyl-3-[5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-YL]-7-(tetrahydrofuran-2-yl)-1H-benzimidazol-2-YL]urea
KR101882172B1 (ko)	2011-01-14	2018-07-26	스페로 트리넴, 인코포레이티드	자이라제 및 토포이소머라제 ⅳ 억제제의 제조방법
ES2576298T3 (es)	2011-06-20	2016-07-06	Vertex Pharmaceuticals Incorporated	Ésteres de fosfato de inhibidores de girasa y topoisomerasa
US9018216B2 (en)	2012-07-18	2015-04-28	Vertex Pharmaceuticals Incorporated	Solid forms of (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof
US9572809B2 (en)	2012-07-18	2017-02-21	Spero Trinem, Inc.	Combination therapy to treat Mycobacterium diseases
GB201506658D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
GB201506660D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
MX2017014613A (es) *	2015-05-15	2018-03-01	Gilead Sciences Inc	Compuestos de bencimidazol e imadazopiridin-carboximidamida que tienen actividad como inhibidores de indolamina 2,3-dioxigenasa.
MX2019000179A (es) *	2016-07-27	2019-06-20	Univ Virginia Patent Foundation	Combinacion de terapias para tratar el cancer.
US20200030295A1 (en) *	2016-08-02	2020-01-30	Friedrich-Alexander-Universität Erlangen-Nürnberg	Heterocyclic diamidines

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1542284A (en) *	1976-01-09	1979-03-14	Barcrest Ltd	Recording electrical information
ES467739A1 (es) *	1977-03-16	1979-07-01	Hoechst Ag	Procedimiento para la preparacion de compuestos de bisbenci-midazolil sustituidos
DE2839989A1 (de) *	1978-09-14	1980-04-03	Hoechst Ag	Substituierte bisbenzimidazolylverbindungen, ihre herstellung und ihre verwendung
US4933347A (en) *	1988-10-25	1990-06-12	University Of North Carolina At Chapel Hill	Diamidines and bis(imidazolines) for the treatment of and prophylaxis against pneumocystis carinii pneumonia
US4963589A (en) *	1988-10-25	1990-10-16	The University Of North Carolina At Chapel Hill	Methods for treating Giardia lamblia
US5134152A (en) *	1989-12-07	1992-07-28	Sankyo Company, Limited	Oxetane derivatives and their use as anti-fungal or fungicidal agents
FR2674246B1 (fr) *	1991-03-21	1993-07-09	Roussel Uclaf	Nouveaux derives de l'acide alpha-methylene 5-thiazolacetique, leur procede de preparation et les intermediaires de ce procede, leur application a titre de fongicides et les compositions les renfermant.
EP0508527A1 (en) *	1991-04-11	1992-10-14	UNIROYAL CHEMICAL COMPANY, Inc.	New fungicidally active pyrazole compounds
US5362910A (en) *	1991-10-08	1994-11-08	Nicca Chemical Co., Ltd.	Germicidal and fungicidal agent and a germicidal and fungicidal method
JPH05140114A (ja) *	1991-11-22	1993-06-08	Otsuka Chem Co Ltd	アゾール−１−カルボン酸エステル誘導体及び殺菌剤
US5428051A (en) *	1992-10-13	1995-06-27	University Of North Carolina	Methods of combating pneumocystis carinii pneumonia and compounds useful therefor
US5667975A (en) *	1994-05-06	1997-09-16	The University Of North Carolina	Method of fluorescent detection of nucleic acids and cytoskeleton elements using bis-dicationic aryl furans

1995
- 1995-06-07 US US08/472,996 patent/US5643935A/en not_active Expired - Fee Related
1996
- 1996-05-01 US US08/641,510 patent/US5639755A/en not_active Expired - Fee Related
- 1996-06-03 EP EP96916817A patent/EP0831832B1/en not_active Expired - Lifetime
- 1996-06-03 DE DE69631134T patent/DE69631134T2/de not_active Expired - Fee Related
- 1996-06-03 AU AU59566/96A patent/AU705261B2/en not_active Ceased
- 1996-06-03 JP JP9500868A patent/JPH11507036A/ja not_active Ceased
- 1996-06-03 CA CA002223912A patent/CA2223912A1/en not_active Abandoned
- 1996-06-03 WO PCT/US1996/008084 patent/WO1996040145A1/en not_active Ceased
- 1996-06-03 ES ES96916817T patent/ES2213775T3/es not_active Expired - Lifetime
- 1996-06-03 AT AT96916817T patent/ATE256464T1/de not_active IP Right Cessation
1997
- 1997-05-29 US US08/865,424 patent/US5792782A/en not_active Expired - Lifetime
- 1997-05-29 US US08/865,425 patent/US5817687A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,427 patent/US5817686A/en not_active Expired - Fee Related
1998
- 1998-08-07 US US09/130,496 patent/US5939440A/en not_active Expired - Fee Related
- 1998-09-01 US US09/145,367 patent/US5972969A/en not_active Expired - Lifetime
- 1998-09-01 US US09/145,368 patent/US6017941A/en not_active Expired - Lifetime
1999
- 1999-07-13 US US09/352,391 patent/US6046226A/en not_active Expired - Lifetime
2000
- 2000-01-04 US US09/477,386 patent/US6156779A/en not_active Expired - Lifetime
- 2000-04-06 US US09/544,643 patent/US6294565B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US5817686A (en)	1998-10-06
WO1996040145A1 (en)	1996-12-19
AU5956696A (en)	1996-12-30
EP0831832A4 (en)	1999-07-07
CA2223912A1 (en)	1996-12-19
ES2213775T3 (es)	2004-09-01
US5939440A (en)	1999-08-17
US5643935A (en)	1997-07-01
US5792782A (en)	1998-08-11
AU705261B2 (en)	1999-05-20
US6046226A (en)	2000-04-04
US6017941A (en)	2000-01-25
EP0831832B1 (en)	2003-12-17
DE69631134D1 (de)	2004-01-29
US5639755A (en)	1997-06-17
US6156779A (en)	2000-12-05
US5817687A (en)	1998-10-06
DE69631134T2 (de)	2004-09-02
US5972969A (en)	1999-10-26
EP0831832A1 (en)	1998-04-01
US6294565B1 (en)	2001-09-25
ATE256464T1 (de)	2004-01-15

Legal Events

Date

Code

Title

Description

2007-02-06

A131

Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20070206

2007-07-19

A313

Final decision of rejection without a dissenting response from the applicant

Free format text: JAPANESE INTERMEDIATE CODE: A313

Effective date: 20070627

2007-08-21

A02

Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20070821

Publication	Publication Date	Title
US6156779A (en)	2000-12-05	Methods of combating infectious diseases using dicatoni bis-benzimidazoles
US5686456A (en)	1997-11-11	Methods of treating pneumocystis carinii pneumonia
EP1143959B1 (en)	2006-11-02	Antifungal activity of dicationic molecules
JP2011500577A (ja)	2011-01-06	バルサルタンの医薬製剤
ES2236734T3 (es)	2005-07-16	Metodos para combatir la neumonia pneumocystis carinii y compuestos utiles para ello.
JPH04264030A (ja)	1992-09-18	抗喘息剤
EP0792271B1 (en)	2002-02-27	Furan derivatives for inhibiting pneumocystis carinii pneumonia, giardia lamblia and cryptosporidium parvum
EP0831811B1 (en)	2003-11-19	Carbazoles for treating microbial infections
US6696441B1 (en)	2004-02-24	Inhibition of p53-induced stress response
CN108774220B (zh)	2019-04-23	用于治疗心肌缺血的化合物及其应用
US20030087899A1 (en)	2003-05-08	Novel methods for the treatment and prevention of pain
EP1685836A2 (en)	2006-08-02	Antifungal activity of dicationic molecules
KR20080014017A (ko)	2008-02-13	(5ｚ)-5-(6-퀴녹살리닐메틸리덴)-2-[(2,6-디클로로페닐)아미노]-1,3-티아졸-4(5ｈ)-온
WO2002094270A2 (en)	2002-11-28	Mip-1 alpha receptor ligands - drugs for t-cell mediated and autoimmune diseases