CA2352592C - Composes quinazolinone - Google Patents

Composes quinazolinone Download PDF

Info

Publication number: CA2352592C
Authority: CA; Canada
Prior art keywords: compound; alkyl; parp; compounds; hydroxy
Prior art date: 1994-03-09
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.): Expired - Fee Related

Application number

CA002352592A

Other languages

English (en)

Other versions

CA2352592A1 (fr

Inventor

Roger John Griffin

Alan Hilary Calvert

Nicola Jane Curtin

David Richard Newell

Bernard Thomas Golding

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Newcastle University Ventures Ltd

Original Assignee

Newcastle University 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.)

1994-03-09

Filing date

1995-03-09

Publication date

2006-06-06

1994-03-09 Priority claimed from GB9404485A external-priority patent/GB9404485D0/en

1995-03-09 Application filed by Newcastle University Ventures Ltd filed Critical Newcastle University Ventures Ltd

1995-09-14 Publication of CA2352592A1 publication Critical patent/CA2352592A1/fr

2006-06-06 Application granted granted Critical

2006-06-06 Publication of CA2352592C publication Critical patent/CA2352592C/fr

2015-03-09 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title claims abstract description 16
150000001875 compounds Chemical class 0.000 claims abstract description 96
102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract description 42
229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 42
101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims abstract description 40
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
102000004190 Enzymes Human genes 0.000 claims abstract description 20
108090000790 Enzymes Proteins 0.000 claims abstract description 20
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 15
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
231100000433 cytotoxic Toxicity 0.000 claims abstract description 13
230000001472 cytotoxic effect Effects 0.000 claims abstract description 13
230000003389 potentiating effect Effects 0.000 claims abstract description 11
238000001959 radiotherapy Methods 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims abstract description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 8
230000001225 therapeutic effect Effects 0.000 claims abstract description 5
102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims abstract description 4
108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims abstract description 4
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
239000001257 hydrogen Substances 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 3
YJDAOHJWLUNFLX-UHFFFAOYSA-N NU 1025 Chemical compound C1=CC=C2C(=O)NC(C)=NC2=C1O YJDAOHJWLUNFLX-UHFFFAOYSA-N 0.000 claims description 43
-1 quinazolinone compound Chemical class 0.000 claims description 25
239000012661 PARP inhibitor Substances 0.000 claims description 24
229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims description 24
230000002401 inhibitory effect Effects 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
229940127089 cytotoxic agent Drugs 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
ZWCBMSNYXIFTCM-UHFFFAOYSA-N 8-methoxy-2-methyl-1h-quinazolin-4-one Chemical compound N1=C(C)NC(=O)C2=C1C(OC)=CC=C2 ZWCBMSNYXIFTCM-UHFFFAOYSA-N 0.000 claims description 8
XMLHWESTKAFTNA-UHFFFAOYSA-N 8-methoxy-2-phenyl-1h-quinazolin-4-one Chemical compound N1=C2C(OC)=CC=CC2=C(O)N=C1C1=CC=CC=C1 XMLHWESTKAFTNA-UHFFFAOYSA-N 0.000 claims description 8
108010049290 ADP Ribose Transferases Proteins 0.000 claims description 8
102000009062 ADP Ribose Transferases Human genes 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
230000005764 inhibitory process Effects 0.000 claims description 7
238000002560 therapeutic procedure Methods 0.000 claims description 7
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
FKPMZNSEGYFIDN-UHFFFAOYSA-N 8-hydroxy-2-(4-nitrophenyl)-1h-quinazolin-4-one Chemical compound OC1=CC=CC(C(N2)=O)=C1N=C2C1=CC=C([N+]([O-])=O)C=C1 FKPMZNSEGYFIDN-UHFFFAOYSA-N 0.000 claims description 6
239000002254 cytotoxic agent Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
230000008707 rearrangement Effects 0.000 claims description 6
CJXMJXBJIWEHRP-UHFFFAOYSA-N 2,8-dimethyl-1h-quinazolin-4-one Chemical compound C1=CC=C2C(=O)NC(C)=NC2=C1C CJXMJXBJIWEHRP-UHFFFAOYSA-N 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
230000000259 anti-tumor effect Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
JRDFYUFZPYBDNH-UHFFFAOYSA-N 8-hydroxy-2-phenyl-1h-quinazolin-4-one Chemical compound OC1=CC=CC(C(N2)=O)=C1N=C2C1=CC=CC=C1 JRDFYUFZPYBDNH-UHFFFAOYSA-N 0.000 claims description 2
231100000599 cytotoxic agent Toxicity 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical group 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
239000000126 substance Substances 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
241000124008 Mammalia Species 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 19
239000003814 drug Substances 0.000 abstract description 15
229940079593 drug Drugs 0.000 abstract description 11
239000003112 inhibitor Substances 0.000 abstract description 9
125000003710 aryl alkyl group Chemical group 0.000 abstract description 7
125000003545 alkoxy group Chemical group 0.000 abstract description 5
125000003107 substituted aryl group Chemical group 0.000 abstract description 4
102000011724 DNA Repair Enzymes Human genes 0.000 abstract 1
108010076525 DNA Repair Enzymes Proteins 0.000 abstract 1
239000000243 solution Substances 0.000 description 42
210000004027 cell Anatomy 0.000 description 36
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 22
238000003556 assay Methods 0.000 description 22
229960004964 temozolomide Drugs 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
238000002360 preparation method Methods 0.000 description 20
238000000034 method Methods 0.000 description 19
GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 13
229960004319 trichloroacetic acid Drugs 0.000 description 13
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
239000002904 solvent Substances 0.000 description 12
238000002474 experimental method Methods 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
231100000135 cytotoxicity Toxicity 0.000 description 10
230000004083 survival effect Effects 0.000 description 10
230000003013 cytotoxicity Effects 0.000 description 9
230000008439 repair process Effects 0.000 description 9
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 8
108091034117 Oligonucleotide Proteins 0.000 description 8
239000000872 buffer Substances 0.000 description 8
238000000921 elemental analysis Methods 0.000 description 8
IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 8
239000000203 mixture Substances 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
239000007787 solid Substances 0.000 description 8
231100001074 DNA strand break Toxicity 0.000 description 7
150000003936 benzamides Chemical class 0.000 description 7
230000009036 growth inhibition Effects 0.000 description 7
238000000338 in vitro Methods 0.000 description 7
229950006238 nadide Drugs 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
238000001914 filtration Methods 0.000 description 6
230000008569 process Effects 0.000 description 6
238000012360 testing method Methods 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
239000006285 cell suspension Substances 0.000 description 5
230000005251 gamma ray Effects 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
230000005855 radiation Effects 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000002002 slurry Substances 0.000 description 5
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 5
229940048086 sodium pyrophosphate Drugs 0.000 description 5
235000019818 tetrasodium diphosphate Nutrition 0.000 description 5
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 5
KTSGITANKLIJRS-UHFFFAOYSA-N 2-amino-3-methoxybenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1N KTSGITANKLIJRS-UHFFFAOYSA-N 0.000 description 4
230000005526 G1 to G0 transition Effects 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
229940054066 benzamide antipsychotics Drugs 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
230000010261 cell growth Effects 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
NGMMGKYJUWYIIG-UHFFFAOYSA-N 3-hydroxybenzamide Chemical compound NC(=O)C1=CC=CC(O)=C1 NGMMGKYJUWYIIG-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
108020004414 DNA Proteins 0.000 description 3
230000005778 DNA damage Effects 0.000 description 3
231100000277 DNA damage Toxicity 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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 3
108091026813 Poly(ADPribose) Proteins 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
230000005025 clonogenic survival Effects 0.000 description 3
230000005757 colony formation Effects 0.000 description 3
230000006378 damage Effects 0.000 description 3
238000010828 elution Methods 0.000 description 3
238000009650 gentamicin protection assay Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
239000002609 medium Substances 0.000 description 3
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 3
238000010899 nucleation Methods 0.000 description 3
239000008188 pellet Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
230000009467 reduction Effects 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
HZIDLPHYFPKXIE-UHFFFAOYSA-N 1,3-benzoxazole-4-carboxamide Chemical class NC(=O)C1=CC=CC2=C1N=CO2 HZIDLPHYFPKXIE-UHFFFAOYSA-N 0.000 description 2
SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical group C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 2
229910015845 BBr3 Inorganic materials 0.000 description 2
125000006519 CCH3 Chemical group 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241001529936 Murinae Species 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
108091081548 Palindromic sequence Proteins 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
239000012190 activator Substances 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
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239000003054 catalyst Substances 0.000 description 2
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229940043239 cytotoxic antineoplastic drug Drugs 0.000 description 2
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229910001629 magnesium chloride Inorganic materials 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
QOQQXWUKTONEOY-UHFFFAOYSA-N methyl 2-(4-nitrophenyl)-1,3-benzoxazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=CC=2OC=1C1=CC=C([N+]([O-])=O)C=C1 QOQQXWUKTONEOY-UHFFFAOYSA-N 0.000 description 2
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UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
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FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
KLOXEYMSPNBMHD-UHFFFAOYSA-N 2-(4-nitrophenyl)-1,3-benzoxazole Chemical class C1=CC([N+](=O)[O-])=CC=C1C1=NC2=CC=CC=C2O1 KLOXEYMSPNBMHD-UHFFFAOYSA-N 0.000 description 1
BRXOIQRFICJYLV-UHFFFAOYSA-N 2-amino-3-methoxybenzamide;3-methoxy-2-nitrobenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1N.COC1=CC=CC(C(N)=O)=C1[N+]([O-])=O BRXOIQRFICJYLV-UHFFFAOYSA-N 0.000 description 1
FEBQTMQGJXZYKX-UHFFFAOYSA-N 2-amino-3-methylbenzamide Chemical compound CC1=CC=CC(C(N)=O)=C1N FEBQTMQGJXZYKX-UHFFFAOYSA-N 0.000 description 1
MZGJDLQJIXSZRB-UHFFFAOYSA-N 3-methoxy-2-nitrobenzamide Chemical compound COC1=CC=CC(C(N)=O)=C1[N+]([O-])=O MZGJDLQJIXSZRB-UHFFFAOYSA-N 0.000 description 1
YMOMYSDAOXOCID-UHFFFAOYSA-N 3-methoxy-2-nitrobenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1[N+]([O-])=O YMOMYSDAOXOCID-UHFFFAOYSA-N 0.000 description 1
SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
QKPZCZRZTKKYRQ-UHFFFAOYSA-N 8-hydroxy-1h-quinazolin-2-one Chemical class C1=NC(=O)NC2=C1C=CC=C2O QKPZCZRZTKKYRQ-UHFFFAOYSA-N 0.000 description 1
PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
102000053602 DNA Human genes 0.000 description 1
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239000012623 DNA damaging agent Substances 0.000 description 1
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229930006000 Sucrose Natural products 0.000 description 1
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ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

CA002352592A 1994-03-09 1995-03-09 Composes quinazolinone Expired - Fee Related CA2352592C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB9404485A GB9404485D0 (en)	1994-03-09	1994-03-09	Benzamide analogues
GB9404485.6		1994-03-09
CA002184747A CA2184747C (fr)	1994-03-09	1995-03-09	Analogues de benzamide, utiles comme inhibiteurs de l'enzyme parp (adp-ribosyltransferase, adprt), reparatrice de l'adn

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002184747A Division CA2184747C (fr)	1994-03-09	1995-03-09	Analogues de benzamide, utiles comme inhibiteurs de l'enzyme parp (adp-ribosyltransferase, adprt), reparatrice de l'adn

Publications (2)

Publication Number	Publication Date
CA2352592A1 CA2352592A1 (fr)	1995-09-14
CA2352592C true CA2352592C (fr)	2006-06-06

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Application Number	Title	Priority Date	Filing Date
CA002352592A Expired - Fee Related CA2352592C (fr)	1994-03-09	1995-03-09	Composes quinazolinone
CA002350941A Abandoned CA2350941A1 (fr)	1994-03-09	1995-03-09	Analogues de benzamide comme inhibiteurs de l'enzyme parp reparatrice de l'adn

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA002350941A Abandoned CA2350941A1 (fr)	1994-03-09	1995-03-09	Analogues de benzamide comme inhibiteurs de l'enzyme parp reparatrice de l'adn

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CA (2)	CA2352592C (fr)

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US20140051737A1 (en) *	2011-05-10	2014-02-20	Universite Laval	Methods for the treatment and diagnostic of pulmonary arterial hypertension

1995
- 1995-03-09 CA CA002352592A patent/CA2352592C/fr not_active Expired - Fee Related
- 1995-03-09 CA CA002350941A patent/CA2350941A1/fr not_active Abandoned

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CA2350941A1 (fr)	1995-09-14

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2008-03-10	MKLA	Lapsed

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