ES2359131T3 - Derivados de ftalazinona. - Google Patents
Derivados de ftalazinona. Download PDFInfo
- Publication number
- ES2359131T3 ES2359131T3 ES01976521T ES01976521T ES2359131T3 ES 2359131 T3 ES2359131 T3 ES 2359131T3 ES 01976521 T ES01976521 T ES 01976521T ES 01976521 T ES01976521 T ES 01976521T ES 2359131 T3 ES2359131 T3 ES 2359131T3
- Authority
- ES
- Spain
- Prior art keywords
- heterocyclyl
- aryl
- ether
- amino
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- -1 amino, sulfonamido Chemical group 0.000 claims abstract description 169
- 150000001875 compounds Chemical class 0.000 claims abstract description 113
- 125000003118 aryl group Chemical group 0.000 claims abstract description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 58
- 125000001424 substituent group Chemical group 0.000 claims abstract description 44
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 150000003568 thioethers Chemical class 0.000 claims abstract description 28
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims abstract description 27
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract description 27
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 27
- 230000000694 effects Effects 0.000 claims abstract description 23
- 150000002148 esters Chemical class 0.000 claims abstract description 19
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 18
- 125000003368 amide group Chemical group 0.000 claims abstract description 18
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- 150000003457 sulfones Chemical class 0.000 claims abstract description 18
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 17
- 150000003462 sulfoxides Chemical class 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 9
- 125000002252 acyl group Chemical group 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 230000003287 optical effect Effects 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- XNBNXFVMQIZMBM-UHFFFAOYSA-N nitroperoxy nitrate Chemical compound [O-][N+](=O)OOO[N+]([O-])=O XNBNXFVMQIZMBM-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000003573 thiols Chemical class 0.000 claims abstract 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 150000003839 salts Chemical group 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 5
- 230000005865 ionizing radiation Effects 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000001174 sulfone group Chemical group 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 238000011275 oncology therapy Methods 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 8
- 239000011780 sodium chloride Substances 0.000 abstract description 5
- 239000000203 mixture Substances 0.000 description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- 239000000243 solution Substances 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 28
- 238000009472 formulation Methods 0.000 description 28
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- 125000006413 ring segment Chemical group 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 125000003277 amino group Chemical group 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- 125000004429 atom Chemical group 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- FAYRFYMUTFVGLI-UHFFFAOYSA-N 5-amino-4-benzyl-2h-phthalazin-1-one Chemical compound NC1=CC=CC(C(NN=2)=O)=C1C=2CC1=CC=CC=C1 FAYRFYMUTFVGLI-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 125000005842 heteroatom Chemical group 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 108010006654 Bleomycin Proteins 0.000 description 7
- 229960001561 bleomycin Drugs 0.000 description 7
- 239000003995 emulsifying agent Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical group 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000000468 ketone group Chemical group 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 125000004430 oxygen atom Chemical group O* 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 239000012258 stirred mixture Substances 0.000 description 6
- RMDVIIZPRLZSOT-UHFFFAOYSA-N 4-benzyl-5-hydroxy-2H-phthalazin-1-one Chemical class OC1=CC=CC(C(NN=2)=O)=C1C=2CC1=CC=CC=C1 RMDVIIZPRLZSOT-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- 239000012661 PARP inhibitor Substances 0.000 description 5
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 238000009795 derivation Methods 0.000 description 5
- 239000003925 fat Substances 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000006072 paste Substances 0.000 description 5
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical class C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 229930194542 Keto Natural products 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000000129 anionic group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 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 4
- 239000000839 emulsion Substances 0.000 description 4
- 208000015756 familial Alzheimer disease Diseases 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000000155 isotopic effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- 0 *N1c2ccccc2CC1C(Oc1cc(CC(c2c3cccc2)=NNC3=*)ccc1)=O Chemical compound *N1c2ccccc2CC1C(Oc1cc(CC(c2c3cccc2)=NNC3=*)ccc1)=O 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 3
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 230000033616 DNA repair Effects 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000002723 alicyclic group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
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- 239000001110 calcium chloride Substances 0.000 description 3
- 235000011148 calcium chloride Nutrition 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 125000005488 carboaryl group Chemical group 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 150000002085 enols Chemical class 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0026505 | 2000-10-30 | ||
| GBGB0026505.8A GB0026505D0 (en) | 2000-10-30 | 2000-10-30 | Phthalazinone derivatives |
| US275066P | 2001-03-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2359131T3 true ES2359131T3 (es) | 2011-05-18 |
Family
ID=9902199
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01976521T Expired - Lifetime ES2359131T3 (es) | 2000-10-30 | 2001-10-25 | Derivados de ftalazinona. |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JP4903355B2 (de) |
| AT (1) | ATE496034T1 (de) |
| DE (1) | DE60143905D1 (de) |
| DK (1) | DK1330442T3 (de) |
| ES (1) | ES2359131T3 (de) |
| GB (1) | GB0026505D0 (de) |
| PT (1) | PT1330442E (de) |
| ZA (1) | ZA200302112B (de) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU228960B1 (hu) * | 2000-10-30 | 2013-07-29 | Kudos Pharm Ltd | Ftalazinon-származékok |
| JP2008510783A (ja) * | 2004-08-26 | 2008-04-10 | クドス ファーマシューティカルズ リミテッド | 4−ヘテロアリールメチル置換フタラジノン誘導体 |
| GB0428111D0 (en) * | 2004-12-22 | 2005-01-26 | Kudos Pharm Ltd | Pthalazinone derivatives |
| ES2548353T3 (es) * | 2006-12-28 | 2015-10-15 | Abbvie Inc. | Inhibidores de poli(ADP-ribosa)polimerasa |
| JP2013532683A (ja) * | 2010-07-27 | 2013-08-19 | カディラ ヘルスケア リミティド | ポリ(adpリボース)ポリメラーゼ−1阻害剤としての、置換4−(4−フルオロ−3−(ピペラジン−1−カルボニル)ベンジル)フタラジン−1(2h)−オン誘導体 |
| CN103130723B (zh) | 2011-11-30 | 2015-01-14 | 成都地奥制药集团有限公司 | 一种多聚(adp-核糖)聚合酶抑制剂 |
| EP2968323A4 (de) * | 2013-03-13 | 2016-12-14 | Flatley Discovery Lab | Pyridazinonverbindungen und verfahren zur behandlung von zystischer fibrose |
-
2000
- 2000-10-30 GB GBGB0026505.8A patent/GB0026505D0/en not_active Ceased
-
2001
- 2001-10-25 DK DK01976521.3T patent/DK1330442T3/da active
- 2001-10-25 DE DE60143905T patent/DE60143905D1/de not_active Expired - Lifetime
- 2001-10-25 PT PT01976521T patent/PT1330442E/pt unknown
- 2001-10-25 AT AT01976521T patent/ATE496034T1/de active
- 2001-10-25 ES ES01976521T patent/ES2359131T3/es not_active Expired - Lifetime
- 2001-10-25 JP JP2002539335A patent/JP4903355B2/ja not_active Expired - Lifetime
-
2003
- 2003-03-17 ZA ZA200302112A patent/ZA200302112B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB0026505D0 (en) | 2000-12-13 |
| PT1330442E (pt) | 2011-04-20 |
| ATE496034T1 (de) | 2011-02-15 |
| DE60143905D1 (de) | 2011-03-03 |
| ZA200302112B (en) | 2004-02-20 |
| JP2004513121A (ja) | 2004-04-30 |
| JP4903355B2 (ja) | 2012-03-28 |
| DK1330442T3 (da) | 2011-04-11 |
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