CA2350941A1 - Analogues de benzamide comme inhibiteurs de l'enzyme parp reparatrice de l'adn - Google Patents

Analogues de benzamide comme inhibiteurs de l'enzyme parp reparatrice de l'adn Download PDF

Info

Publication number: CA2350941A1
Authority: CA; Canada
Prior art keywords: compound; carboxamide; alkyl; parp; compounds
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.): Abandoned

Application number

CA002350941A

Other languages

English (en)

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

Individual

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

1995-09-14

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

1995-03-09 Application filed by Individual filed Critical Individual

1995-09-14 Publication of CA2350941A1 publication Critical patent/CA2350941A1/fr

Status Abandoned legal-status Critical Current

Links

150000003936 benzamides Chemical class 0.000 title abstract description 11
102000011724 DNA Repair Enzymes Human genes 0.000 title abstract 2
108010076525 DNA Repair Enzymes Proteins 0.000 title abstract 2
239000002532 enzyme inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 85
102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract description 37
229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 37
101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims abstract description 35
102000004190 Enzymes Human genes 0.000 claims abstract description 20
108090000790 Enzymes Proteins 0.000 claims abstract description 20
125000000217 alkyl group Chemical group 0.000 claims abstract description 16
239000003814 drug Substances 0.000 claims abstract description 14
125000003118 aryl group Chemical group 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 11
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
230000001225 therapeutic effect Effects 0.000 claims abstract description 5
HZIDLPHYFPKXIE-UHFFFAOYSA-N 1,3-benzoxazole-4-carboxamide Chemical class NC(=O)C1=CC=CC2=C1N=CO2 HZIDLPHYFPKXIE-UHFFFAOYSA-N 0.000 claims abstract description 4
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
-1 benzoxazole-4-carboxamide compound Chemical class 0.000 claims description 22
230000002401 inhibitory effect Effects 0.000 claims description 19
239000008194 pharmaceutical composition Substances 0.000 claims description 10
FFTBZJKGYRMFHQ-UHFFFAOYSA-N 2-methyl-1,3-benzoxazole-4-carboxamide Chemical compound C1=CC=C2OC(C)=NC2=C1C(N)=O FFTBZJKGYRMFHQ-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
229940127089 cytotoxic agent Drugs 0.000 claims description 7
230000005764 inhibitory process Effects 0.000 claims description 7
238000011282 treatment Methods 0.000 claims description 7
KTVVJXLUQDPXAB-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1,3-benzoxazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=NC2=C(C(N)=O)C=CC=C2O1 KTVVJXLUQDPXAB-UHFFFAOYSA-N 0.000 claims description 6
RMVXDWHQMBASON-UHFFFAOYSA-N 2-phenyl-1,3-benzoxazole-4-carboxamide Chemical compound N=1C=2C(C(=O)N)=CC=CC=2OC=1C1=CC=CC=C1 RMVXDWHQMBASON-UHFFFAOYSA-N 0.000 claims description 6
238000002560 therapeutic procedure Methods 0.000 claims description 6
BRRCJXBWNQBJOY-UHFFFAOYSA-N 2-tert-butyl-1,3-benzoxazole-4-carboxamide Chemical compound C1=CC=C2OC(C(C)(C)C)=NC2=C1C(N)=O BRRCJXBWNQBJOY-UHFFFAOYSA-N 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
239000002254 cytotoxic agent Substances 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
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125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
239000012661 PARP inhibitor Substances 0.000 description 11
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
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239000000047 product Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
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 7
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125000001424 substituent group Chemical group 0.000 description 6
238000012360 testing method Methods 0.000 description 6
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical class NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
230000005855 radiation Effects 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
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
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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 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-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
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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
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BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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AUZVVSMHJHRXSD-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)-1,3-benzoxazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=CC=2OC=1C1=CC=C(OC)C=C1 AUZVVSMHJHRXSD-UHFFFAOYSA-N 0.000 description 1
NXYOCMUHXDRQJP-UHFFFAOYSA-N methyl 2-(4-nitrophenyl)-1,3-benzoxazole-4-carboxylate;2-(4-nitrophenyl)-1,3-benzoxazole-4-carboxylic acid Chemical compound N=1C=2C(C(=O)O)=CC=CC=2OC=1C1=CC=C([N+]([O-])=O)C=C1.N=1C=2C(C(=O)OC)=CC=CC=2OC=1C1=CC=C([N+]([O-])=O)C=C1 NXYOCMUHXDRQJP-UHFFFAOYSA-N 0.000 description 1
OBVQJFCAYWKRBZ-UHFFFAOYSA-N methyl 2-amino-3-hydroxybenzoate;methyl 3-hydroxy-2-[(4-nitrobenzoyl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(O)=C1N.COC(=O)C1=CC=CC(O)=C1NC(=O)C1=CC=C([N+]([O-])=O)C=C1 OBVQJFCAYWKRBZ-UHFFFAOYSA-N 0.000 description 1
ULCYIMXEMJLOOA-UHFFFAOYSA-N methyl 3-hydroxy-2-[(4-nitrobenzoyl)amino]benzoate;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.COC(=O)C1=CC=CC(O)=C1NC(=O)C1=CC=C([N+]([O-])=O)C=C1 ULCYIMXEMJLOOA-UHFFFAOYSA-N 0.000 description 1
FHCNMPYMCKHBTK-UHFFFAOYSA-N methyl 3-hydroxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC=CC(O)=C1[N+]([O-])=O FHCNMPYMCKHBTK-UHFFFAOYSA-N 0.000 description 1
230000001035 methylating effect Effects 0.000 description 1
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238000012986 modification Methods 0.000 description 1
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FVLVBVSILSHUAF-UHFFFAOYSA-N n-benzyl-3,5-dimethyl-n-propan-2-ylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(C(C)C)CC1=CC=CC=C1 FVLVBVSILSHUAF-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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239000011570 nicotinamide Substances 0.000 description 1
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108090000623 proteins and genes Proteins 0.000 description 1
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230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1

Landscapes

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

CA002350941A 1994-03-09 1995-03-09 Analogues de benzamide comme inhibiteurs de l'enzyme parp reparatrice de l'adn Abandoned CA2350941A1 (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 (1)

Publication Number	Publication Date
CA2350941A1 true CA2350941A1 (fr)	1995-09-14

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

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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

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CA (2)	CA2350941A1 (fr)

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CA2833914A1 (fr) *	2011-05-10	2012-11-15	Universite Laval	Procedes pour le traitement et le diagnostic de l'hypertension arterielle pulmonaire

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

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CA2352592C (fr)	2006-06-06

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Publication	Publication Date	Title
EP0879820B1 (fr)	2001-12-12	Analogues de benzamide utile pour en tant au'inhibiteurs de l'enzyme parp (adp-ribosyltransferase, adprt) de réparation de l'adn
US6100283A (en)	2000-08-08	Benzimidazole compounds
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