OA10661A - Benzimidazole compounds - Google Patents

Benzimidazole compounds Download PDF

Info

Publication number: OA10661A
Authority: OA; OAPI
Prior art keywords: alkyl; benzimidazole; carboxamide; compound; group
Prior art date: 1995-08-02

Application number

OA9800017A

Other languages

English (en)

Inventor

Roger John Griffin

Alan Hilary Calvert

Nicola Jane Curtin

David Richard Newell

Bernard Thomas Golding

Original Assignee

Univ Newcastle Ventures Ltd

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.)

1995-08-02

Filing date

1998-01-30

Publication date

2002-11-25

1995-08-02 Priority claimed from GBGB9515843.2A external-priority patent/GB9515843D0/en

1996-05-30 Priority claimed from GBGB9611245.3A external-priority patent/GB9611245D0/en

1998-01-30 Application filed by Univ Newcastle Ventures Ltd filed Critical Univ Newcastle Ventures Ltd

2002-11-25 Publication of OA10661A publication Critical patent/OA10661A/en

Links

125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 95
125000000217 alkyl group Chemical group 0.000 claims abstract description 51
-1 CH2CH2OH) Chemical class 0.000 claims abstract description 42
102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract description 32
229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 32
JJDMKDXGNVJWCD-UHFFFAOYSA-N 1h-benzimidazole-4-carboxamide Chemical class NC(=O)C1=CC=CC2=C1N=CN2 JJDMKDXGNVJWCD-UHFFFAOYSA-N 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 31
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
108090000790 Enzymes Proteins 0.000 claims abstract description 16
102000004190 Enzymes Human genes 0.000 claims abstract description 16
239000000651 prodrug Substances 0.000 claims abstract description 16
229940002612 prodrug Drugs 0.000 claims abstract description 16
230000000694 effects Effects 0.000 claims abstract description 15
239000003814 drug Substances 0.000 claims abstract description 13
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 11
229940079593 drug Drugs 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 10
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 9
125000002252 acyl group Chemical group 0.000 claims abstract description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 8
238000001959 radiotherapy Methods 0.000 claims abstract description 8
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 8
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims abstract description 7
230000001225 therapeutic effect Effects 0.000 claims abstract description 6
102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims abstract description 3
108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims abstract description 3
125000003710 aryl alkyl group Chemical group 0.000 claims abstract 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
239000000203 mixture Substances 0.000 claims description 17
230000002401 inhibitory effect Effects 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 15
238000000034 method Methods 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
229910019142 PO4 Inorganic materials 0.000 claims description 11
125000003118 aryl group Chemical group 0.000 claims description 11
239000010452 phosphate Substances 0.000 claims description 11
150000003536 tetrazoles Chemical class 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
229940127089 cytotoxic agent Drugs 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 9
JCMGIFLIMIXLTP-UHFFFAOYSA-N 2-methyl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C(N)=O)=C2NC(C)=NC2=C1 JCMGIFLIMIXLTP-UHFFFAOYSA-N 0.000 claims description 8
238000002560 therapeutic procedure Methods 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
239000002254 cytotoxic agent Substances 0.000 claims description 7
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 6
OBBJGEVEIULNEO-UHFFFAOYSA-N 2-phenyl-1h-benzimidazole-4-carboxamide Chemical compound N=1C=2C(C(=O)N)=CC=CC=2NC=1C1=CC=CC=C1 OBBJGEVEIULNEO-UHFFFAOYSA-N 0.000 claims description 6
108010049290 ADP Ribose Transferases Proteins 0.000 claims description 6
102000009062 ADP Ribose Transferases Human genes 0.000 claims description 6
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
150000003857 carboxamides Chemical class 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
230000005764 inhibitory process Effects 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
MKRGNKRNZLHINT-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=CC(C(N)=O)=C2N1 MKRGNKRNZLHINT-UHFFFAOYSA-N 0.000 claims description 5
150000001408 amides Chemical class 0.000 claims description 5
KOUGHMOSYJCJLE-UHFFFAOYSA-N chembl131719 Chemical compound N=1C=2C(C(=O)N)=CC=CC=2NC=1C1=CC=C(O)C=C1 KOUGHMOSYJCJLE-UHFFFAOYSA-N 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
NVVWVYYHTKCIAE-UHFFFAOYSA-N 2-(3'-methoxyphenyl) benzimidazole-4-carboxamide Chemical compound COC1=CC=CC(C=2NC3=CC=CC(=C3N=2)C(N)=O)=C1 NVVWVYYHTKCIAE-UHFFFAOYSA-N 0.000 claims description 3
PMISIOUALHNLES-UHFFFAOYSA-N 2-[2-(trifluoromethyl)phenyl]-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(C(=O)N)=CC=CC=2N=C1C1=CC=CC=C1C(F)(F)F PMISIOUALHNLES-UHFFFAOYSA-N 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
150000001413 amino acids Chemical class 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 claims description 3
150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 3
238000007363 ring formation reaction Methods 0.000 claims description 3
VANPTVOCOWCFLO-UHFFFAOYSA-N 2-(trifluoromethyl)-1h-benzimidazole-4-carboxamide Chemical compound NC(=O)C1=CC=CC2=C1NC(C(F)(F)F)=N2 VANPTVOCOWCFLO-UHFFFAOYSA-N 0.000 claims description 2
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
235000010290 biphenyl Nutrition 0.000 claims description 2
239000004305 biphenyl Substances 0.000 claims description 2
125000006267 biphenyl group Chemical group 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
239000002552 dosage form Substances 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
239000003513 alkali Substances 0.000 claims 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
DSPHFASHOJAOKN-UHFFFAOYSA-N 1-[(7-oxobenzo[a]phenalen-2-yl)amino]anthracene-9,10-dione Chemical compound C1=CC2=CC(NC3=C4C(=O)C5=CC=CC=C5C(C4=CC=C3)=O)=CC(C=3C(=CC=CC=3)C3=O)=C2C3=C1 DSPHFASHOJAOKN-UHFFFAOYSA-N 0.000 claims 1
XIQDETZLOXHMNE-UHFFFAOYSA-N 1-benzoyl-2-(4-methoxyphenyl)benzimidazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=C(C(N)=O)C=CC=C2N1C(=O)C1=CC=CC=C1 XIQDETZLOXHMNE-UHFFFAOYSA-N 0.000 claims 1
AKWIAIDKXNKXDI-UHFFFAOYSA-N 1h-pyrrole-3-carboxamide Chemical compound NC(=O)C=1C=CNC=1 AKWIAIDKXNKXDI-UHFFFAOYSA-N 0.000 claims 1
KXFVEKRQOAGNIL-UHFFFAOYSA-N 2-(4-methoxyphenyl)-n-methyl-1h-benzimidazole-4-carboxamide Chemical compound N1C=2C(C(=O)NC)=CC=CC=2N=C1C1=CC=C(OC)C=C1 KXFVEKRQOAGNIL-UHFFFAOYSA-N 0.000 claims 1
244000182067 Fraxinus ornus Species 0.000 claims 1
102000004357 Transferases Human genes 0.000 claims 1
108090000992 Transferases Proteins 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
150000002460 imidazoles Chemical class 0.000 claims 1
239000007788 liquid Substances 0.000 claims 1
101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 abstract description 29
239000003112 inhibitor Substances 0.000 abstract description 8
230000003389 potentiating effect Effects 0.000 abstract description 7
231100000433 cytotoxic Toxicity 0.000 abstract description 6
230000001472 cytotoxic effect Effects 0.000 abstract description 6
150000003839 salts Chemical class 0.000 abstract description 3
102000011724 DNA Repair Enzymes Human genes 0.000 abstract 1
108010076525 DNA Repair Enzymes Proteins 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 98
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 50
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
239000000243 solution Substances 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
210000004027 cell Anatomy 0.000 description 29
239000007787 solid Substances 0.000 description 28
239000002904 solvent Substances 0.000 description 25
238000010561 standard procedure Methods 0.000 description 25
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
238000003556 assay Methods 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
229940093499 ethyl acetate Drugs 0.000 description 16
235000019439 ethyl acetate Nutrition 0.000 description 16
238000001953 recrystallisation Methods 0.000 description 16
229940064734 aminobenzoate Drugs 0.000 description 15
239000000047 product Substances 0.000 description 15
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
BLJHLOLVEXWHFS-UHFFFAOYSA-N methyl 2,3-diaminobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1N BLJHLOLVEXWHFS-UHFFFAOYSA-N 0.000 description 13
239000012661 PARP inhibitor Substances 0.000 description 12
229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 12
229960004964 temozolomide Drugs 0.000 description 12
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 12
229960004319 trichloroacetic acid Drugs 0.000 description 12
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 10
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
230000008439 repair process Effects 0.000 description 8
238000012360 testing method Methods 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
229940086542 triethylamine Drugs 0.000 description 8
239000000872 buffer Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
229960000443 hydrochloric acid Drugs 0.000 description 7
235000011167 hydrochloric acid Nutrition 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
230000004083 survival effect Effects 0.000 description 7
KKTUQAYCCLMNOA-UHFFFAOYSA-N 2,3-diaminobenzoic acid Chemical compound NC1=CC=CC(C(O)=O)=C1N KKTUQAYCCLMNOA-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 6
108091034117 Oligonucleotide Proteins 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
238000010992 reflux Methods 0.000 description 6
229960000549 4-dimethylaminophenol Drugs 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
235000011114 ammonium hydroxide Nutrition 0.000 description 5
150000003936 benzamides Chemical class 0.000 description 5
238000009835 boiling Methods 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
239000006285 cell suspension Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000002609 medium Substances 0.000 description 5
230000008569 process Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000002253 acid Substances 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
150000001556 benzimidazoles Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000003013 cytotoxicity Effects 0.000 description 4
231100000135 cytotoxicity Toxicity 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
HDCLJQZLTMJECA-UHFFFAOYSA-N methyl 2-amino-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1N HDCLJQZLTMJECA-UHFFFAOYSA-N 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 4
229940048086 sodium pyrophosphate Drugs 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
235000019818 tetrasodium diphosphate Nutrition 0.000 description 4
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 4
VVQNAFBGAWCMLU-UHFFFAOYSA-N 1h-benzimidazole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1N=CN2 VVQNAFBGAWCMLU-UHFFFAOYSA-N 0.000 description 3
JJPIVRWTAGQTPQ-UHFFFAOYSA-N 2-amino-3-nitrobenzoic acid Chemical compound NC1=C(C(O)=O)C=CC=C1[N+]([O-])=O JJPIVRWTAGQTPQ-UHFFFAOYSA-N 0.000 description 3
IGLWGHRTQOYFDV-UHFFFAOYSA-N 2-carbamoyl-3-nitrobenzoic acid Chemical compound NC(=O)C1=C(C(O)=O)C=CC=C1[N+]([O-])=O IGLWGHRTQOYFDV-UHFFFAOYSA-N 0.000 description 3
VKPLPDIMEREJJF-UHFFFAOYSA-N 3-methoxybenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1 VKPLPDIMEREJJF-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
108020004414 DNA Proteins 0.000 description 3
230000005778 DNA damage Effects 0.000 description 3
231100000277 DNA damage Toxicity 0.000 description 3
231100001074 DNA strand break Toxicity 0.000 description 3
230000005526 G1 to G0 transition Effects 0.000 description 3
208000001953 Hypotension Diseases 0.000 description 3
241001529936 Murinae Species 0.000 description 3
108091026813 Poly(ADPribose) Proteins 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
230000005757 colony formation Effects 0.000 description 3
239000012043 crude product Substances 0.000 description 3
230000009036 growth inhibition Effects 0.000 description 3
208000032839 leukemia Diseases 0.000 description 3
239000000463 material Substances 0.000 description 3
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
230000005855 radiation Effects 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
LVUZVFVJPPDROZ-UHFFFAOYSA-N 2-methyl-1h-benzimidazole-4-carboxylic acid Chemical compound C1=CC(C(O)=O)=C2NC(C)=NC2=C1 LVUZVFVJPPDROZ-UHFFFAOYSA-N 0.000 description 2
GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 2
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Classifications

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- 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
- A61K31/415—1,2-Diazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- A—HUMAN NECESSITIES
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- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/10—Radicals substituted by halogen atoms or nitro radicals
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
- C—CHEMISTRY; METALLURGY
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2

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OA9800017A 1995-08-02 1998-01-30 Benzimidazole compounds OA10661A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9515843.2A GB9515843D0 (en)	1995-08-02	1995-08-02	Benzimidazole compounds
GBGB9611245.3A GB9611245D0 (en)	1996-05-30	1996-05-30	Benzimidazole compounds

Publications (1)

Publication Number	Publication Date
OA10661A true OA10661A (en)	2002-11-25

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ID=26307504

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9800017A OA10661A (en)	1995-08-02	1998-01-30	Benzimidazole compounds

Country Status (26)

Country	Link
US (2)	US6100283A (de)
EP (1)	EP0841924B1 (de)
JP (1)	JPH11510154A (de)
KR (1)	KR100447539B1 (de)
CN (1)	CN1159007C (de)
AP (1)	AP866A (de)
AT (1)	ATE225173T1 (de)
AU (1)	AU714873B2 (de)
BR (1)	BR9610051A (de)
CA (1)	CA2225465A1 (de)
CZ (1)	CZ30398A3 (de)
DE (1)	DE69624115T2 (de)
DK (1)	DK0841924T3 (de)
EA (1)	EA000999B1 (de)
ES (1)	ES2183004T3 (de)
HU (1)	HUP9901092A3 (de)
IL (1)	IL123147A (de)
MX (1)	MX9800927A (de)
NO (1)	NO317033B1 (de)
NZ (1)	NZ313713A (de)
OA (1)	OA10661A (de)
PL (1)	PL324869A1 (de)
PT (1)	PT841924E (de)
SK (1)	SK13598A3 (de)
TR (1)	TR199800127T1 (de)
WO (1)	WO1997004771A1 (de)

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1996
- 1996-07-30 EP EP96925875A patent/EP0841924B1/de not_active Expired - Lifetime
- 1996-07-30 SK SK135-98A patent/SK13598A3/sk unknown
- 1996-07-30 DK DK96925875T patent/DK0841924T3/da active
- 1996-07-30 ES ES96925875T patent/ES2183004T3/es not_active Expired - Lifetime
- 1996-07-30 HU HU9901092A patent/HUP9901092A3/hu not_active Application Discontinuation
- 1996-07-30 WO PCT/GB1996/001832 patent/WO1997004771A1/en not_active Ceased
- 1996-07-30 AP APAP/P/1998/001183A patent/AP866A/en active
- 1996-07-30 PL PL96324869A patent/PL324869A1/xx unknown
- 1996-07-30 IL IL12314796A patent/IL123147A/en not_active IP Right Cessation
- 1996-07-30 PT PT96925875T patent/PT841924E/pt unknown
- 1996-07-30 AU AU66240/96A patent/AU714873B2/en not_active Ceased
- 1996-07-30 KR KR10-1998-0700752A patent/KR100447539B1/ko not_active Expired - Fee Related
- 1996-07-30 CZ CZ98303A patent/CZ30398A3/cs unknown
- 1996-07-30 DE DE69624115T patent/DE69624115T2/de not_active Expired - Fee Related
- 1996-07-30 CA CA002225465A patent/CA2225465A1/en not_active Abandoned
- 1996-07-30 EA EA199800184A patent/EA000999B1/ru not_active IP Right Cessation
- 1996-07-30 TR TR1998/00127T patent/TR199800127T1/xx unknown
- 1996-07-30 BR BR9610051-6A patent/BR9610051A/pt not_active Application Discontinuation
- 1996-07-30 JP JP9507360A patent/JPH11510154A/ja not_active Ceased
- 1996-07-30 AT AT96925875T patent/ATE225173T1/de not_active IP Right Cessation
- 1996-07-30 NZ NZ313713A patent/NZ313713A/en unknown
- 1996-07-31 CN CNB961968818A patent/CN1159007C/zh not_active Expired - Fee Related
1998
- 1998-01-30 NO NO19980414A patent/NO317033B1/no not_active IP Right Cessation
- 1998-01-30 OA OA9800017A patent/OA10661A/en unknown
- 1998-02-02 US US09/017,314 patent/US6100283A/en not_active Expired - Fee Related
- 1998-02-02 MX MX9800927A patent/MX9800927A/es not_active IP Right Cessation
2000
- 2000-06-16 US US09/594,776 patent/US6310082B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HUP9901092A2 (hu)	1999-07-28
JPH11510154A (ja)	1999-09-07
IL123147A0 (en)	1998-09-24
BR9610051A (pt)	1999-12-21
AP866A (en)	2000-08-17
NO980414L (no)	1998-04-02
NZ313713A (en)	2001-03-30
AU6624096A (en)	1997-02-26
US6100283A (en)	2000-08-08
NO980414D0 (no)	1998-01-30
PL324869A1 (en)	1998-06-22
CN1159007C (zh)	2004-07-28
ATE225173T1 (de)	2002-10-15
NO317033B1 (no)	2004-07-26
MX9800927A (es)	1998-10-31
CA2225465A1 (en)	1997-02-13
KR19990036086A (ko)	1999-05-25
EA000999B1 (ru)	2000-08-28
IL123147A (en)	2004-02-19
EA199800184A1 (ru)	1998-10-29
SK13598A3 (en)	1998-06-03
US6310082B1 (en)	2001-10-30
CN1195985A (zh)	1998-10-14
WO1997004771A1 (en)	1997-02-13
ES2183004T3 (es)	2003-03-16
DE69624115T2 (de)	2003-06-18
EP0841924B1 (de)	2002-10-02
EP0841924A1 (de)	1998-05-20
AP9801183A0 (en)	1998-01-31
PT841924E (pt)	2003-02-28
KR100447539B1 (ko)	2004-11-10
CZ30398A3 (cs)	1998-06-17
TR199800127T1 (xx)	1998-04-21
DK0841924T3 (da)	2003-02-10
DE69624115D1 (de)	2002-11-07
AU714873B2 (en)	2000-01-13
HUP9901092A3 (en)	2001-11-28

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