JPH09512539A - ジヒドロジベンゾ（ｄｅ，ｈ）イソキノリン誘導体および抗癌剤としての該誘導体の使用 - Google Patents
ジヒドロジベンゾ（ｄｅ，ｈ）イソキノリン誘導体および抗癌剤としての該誘導体の使用Info
- Publication number
- JPH09512539A JPH09512539A JP7527954A JP52795495A JPH09512539A JP H09512539 A JPH09512539 A JP H09512539A JP 7527954 A JP7527954 A JP 7527954A JP 52795495 A JP52795495 A JP 52795495A JP H09512539 A JPH09512539 A JP H09512539A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- dihydro
- compound
- bis
- 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.)
- Ceased
Links
- 239000002246 antineoplastic agent Substances 0.000 title description 2
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 3
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract 2
- 125000001302 tertiary amino 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 9
- KSQMWIGJIDTOFT-UHFFFAOYSA-N anthracene-1,9-dicarboxylic anhydride Chemical compound C1=CC(C(=O)OC2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 KSQMWIGJIDTOFT-UHFFFAOYSA-N 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- CKWYOIKYTYWDDP-UHFFFAOYSA-N C1(=CC=CC2=CC3=CC=CC=C3C(=C12)C(=O)O)C(=O)N Chemical compound C1(=CC=CC2=CC3=CC=CC=C3C(=C12)C(=O)O)C(=O)N CKWYOIKYTYWDDP-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
- 229910052757 nitrogen Inorganic materials 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 238000002844 melting Methods 0.000 description 26
- 230000008018 melting Effects 0.000 description 26
- -1 1,2-dihydro-1,3-dioxo-3H-dibenz [De, h] isoquinolin-2-yl Chemical group 0.000 description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 7
- PGCKQBLIVWMPFF-UHFFFAOYSA-N n,n'-bis[2-(1,2-dihydro-1,3-dioxo-3h-dibenz[de,h]isoquinolin-2-yl)ethyl]-1,3-propanediamine Chemical compound C1=CC(C(=O)N(CCNCCCNCCN2C(C=3C4=CC=CC=C4C=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 PGCKQBLIVWMPFF-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical compound C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 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
- 241000124008 Mammalia Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QBPVGVFLUWAMEQ-UHFFFAOYSA-N 2-(2-hydroxyethyl)-1,2-dihydro-3h-dibenz[de,h]isoquinoline-1,3-dione Chemical compound C1=CC=C2C(C(N(CCO)C3=O)=O)=C4C3=CC=CC4=CC2=C1 QBPVGVFLUWAMEQ-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 229930182556 Polyacetal Natural products 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 241000143950 Vanessa Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- RSPOEUCVQSNRRK-UHFFFAOYSA-N ac1l7a3j Chemical compound C1=CC(C(=O)N(CCCNCCNCCCN2C(C=3C4=CC=CC=C4C=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 RSPOEUCVQSNRRK-UHFFFAOYSA-N 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- VFZBASYBHQKISE-UHFFFAOYSA-N chembl140742 Chemical compound C1=CC=C2C(C(N(CCN(CCN(C)CCN3C(C=4C5=CC=CC=C5C=C5C=CC=C(C=45)C3=O)=O)C)C3=O)=O)=C4C3=CC=CC4=CC2=C1 VFZBASYBHQKISE-UHFFFAOYSA-N 0.000 description 1
- SJLDCYXKABNRSN-UHFFFAOYSA-N chembl141593 Chemical compound C1=CC(C(=O)N(CCCNCCCNCCCN2C(C=3C4=CC=CC=C4C=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 SJLDCYXKABNRSN-UHFFFAOYSA-N 0.000 description 1
- MWWJJXMLIVMYCR-UHFFFAOYSA-N chembl141972 Chemical compound C1=CC(C(=O)N(CCNCCCCCNCCN2C(C=3C4=CC=CC=C4C=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 MWWJJXMLIVMYCR-UHFFFAOYSA-N 0.000 description 1
- GQOTWFRUVRGNFF-UHFFFAOYSA-N chembl142086 Chemical compound C1=CC(C(=O)N(CCNCCNCCN2C(C=3C4=CC=CC=C4C=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 GQOTWFRUVRGNFF-UHFFFAOYSA-N 0.000 description 1
- RNJCIKCVFDNGIU-UHFFFAOYSA-N chembl335553 Chemical compound C1=CC=C2C(C(N(CCCN(CCCN3C(C=4C5=CC=CC=C5C=C5C=CC=C(C=45)C3=O)=O)C)C3=O)=O)=C4C3=CC=CC4=CC2=C1 RNJCIKCVFDNGIU-UHFFFAOYSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- SCCWFEKONJHQAC-UHFFFAOYSA-N n,n'-bis[2-(1,2-dihydro-1,3-dioxo-3h-dibenz[de,h]isoquinolin-2-yl)ethyl]hexahydropyrimidine Chemical compound C1=CC(C(=O)N(CCN2CN(CCN3C(C=4C5=CC=CC=C5C=C5C=CC=C(C=45)C3=O)=O)CCC2)C2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 SCCWFEKONJHQAC-UHFFFAOYSA-N 0.000 description 1
- HJFIJDDDBZCGTN-UHFFFAOYSA-N n-[2-(1,2-dihydro-1,3-dioxo-3h-dibenz[de,h]isoquinolin-2-yl)ethyl]-n'-(2-aminoethyl)-1,3-propanediamine Chemical compound C1=CC=C2C(C(N(CCNCCCNCCN)C3=O)=O)=C4C3=CC=CC4=CC2=C1 HJFIJDDDBZCGTN-UHFFFAOYSA-N 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- GSWAOPJLTADLTN-UHFFFAOYSA-N oxidanimine Chemical compound [O-][NH3+] GSWAOPJLTADLTN-UHFFFAOYSA-N 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23399894A | 1994-04-28 | 1994-04-28 | |
| US08/233,998 | 1994-04-28 | ||
| PCT/EP1995/001347 WO1995029895A1 (en) | 1994-04-28 | 1995-04-12 | Dihydrodibenzo(de,h)isoquinolines derivatives and their use as anti-cancer agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09512539A true JPH09512539A (ja) | 1997-12-16 |
Family
ID=22879465
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7527954A Ceased JPH09512539A (ja) | 1994-04-28 | 1995-04-12 | ジヒドロジベンゾ（ｄｅ，ｈ）イソキノリン誘導体および抗癌剤としての該誘導体の使用 |
Country Status (11)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6121278A (en) * | 1997-09-03 | 2000-09-19 | Guilford Pharmaceuticals, Inc. | Di-n-heterocyclic compounds, methods, and compositions for inhibiting parp activity |
| US6197785B1 (en) | 1997-09-03 | 2001-03-06 | Guilford Pharmaceuticals Inc. | Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity |
| US6291425B1 (en) | 1999-09-01 | 2001-09-18 | Guilford Pharmaceuticals Inc. | Compounds, methods and pharmaceutical compositions for treating cellular damage, such as neural or cardiovascular tissue damage |
| US6380193B1 (en) | 1998-05-15 | 2002-04-30 | Guilford Pharmaceuticals Inc. | Fused tricyclic compounds, methods and compositions for inhibiting PARP activity |
| PT103503B (pt) * | 2006-06-19 | 2009-05-18 | Univ Do Porto | Novos derivados do bisnaftalimidopropil, processo para a sua preparação, composições farmacêuticas que os contêm e sua utilização em doenças cancerígenas e parasitárias, nomeadamente leishmanioses, tripanossomíases e malária. |
| CN101638389B (zh) * | 2008-03-03 | 2012-09-05 | 河南大学 | 一种含萘酰亚胺结构的多胺衍生物及其制备方法和应用 |
| CN117074567B (zh) * | 2023-08-25 | 2025-06-27 | 四川汇宇制药股份有限公司 | 高效液相色谱法检测氨磷汀中间体纯度及其有关物质的方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0125439B1 (en) * | 1983-04-01 | 1990-01-24 | Warner-Lambert Company | 3,6-disubstituted-1,8-naphthalimides and methods for their production and use |
| DE3707651A1 (de) * | 1987-03-10 | 1988-09-22 | Knoll Ag | Bis-naphthalimide, ihre herstellung und verwendung |
| WO1992000281A1 (en) * | 1990-06-26 | 1992-01-09 | Research Corporation Technologies, Inc. | 1,2-dihydro-3h-dibenzisoquinoline-1,3-dione anticancer agents |
| EP0660824A1 (en) * | 1992-09-11 | 1995-07-05 | Research Corporation Technologies | 1,2 DIHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3 DIONE AND THEIR USE AS ANTICANCER AGENTS |
| DE4232739A1 (de) * | 1992-09-30 | 1994-03-31 | Knoll Ag | Neue asymmetrisch substituierte bis-Naphthalimide |
-
1995
- 1995-04-12 JP JP7527954A patent/JPH09512539A/ja not_active Ceased
- 1995-04-12 CN CN95193192A patent/CN1092185C/zh not_active Expired - Fee Related
- 1995-04-12 SG SG1996008471A patent/SG73418A1/en unknown
- 1995-04-12 CA CA002188833A patent/CA2188833A1/en not_active Abandoned
- 1995-04-12 AU AU23065/95A patent/AU2306595A/en not_active Abandoned
- 1995-04-12 WO PCT/EP1995/001347 patent/WO1995029895A1/en not_active Application Discontinuation
- 1995-04-12 EP EP95916636A patent/EP0757676A1/en not_active Withdrawn
- 1995-04-18 TW TW084103805A patent/TW307764B/zh active
- 1995-04-18 IL IL11341595A patent/IL113415A/xx not_active IP Right Cessation
- 1995-04-25 HR HR08/233,998A patent/HRP950250A2/hr not_active Application Discontinuation
- 1995-04-26 ZA ZA953379A patent/ZA953379B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL113415A (en) | 1999-11-30 |
| CN1148851A (zh) | 1997-04-30 |
| IL113415A0 (en) | 1995-07-31 |
| AU2306595A (en) | 1995-11-29 |
| ZA953379B (en) | 1996-10-28 |
| CN1092185C (zh) | 2002-10-09 |
| EP0757676A1 (en) | 1997-02-12 |
| CA2188833A1 (en) | 1995-11-09 |
| WO1995029895A1 (en) | 1995-11-09 |
| TW307764B (enrdf_load_stackoverflow) | 1997-06-11 |
| SG73418A1 (en) | 2000-06-20 |
| HRP950250A2 (en) | 1997-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3391796B2 (ja) | 新規化合物、その製法および抗腫瘍剤 | |
| CN1039414C (zh) | 双萘二甲酰亚胺类化合物 | |
| JPS6225670B2 (enrdf_load_stackoverflow) | ||
| US5416089A (en) | Polycyclic and heterocyclic chromophores for bis-imide tumoricidals | |
| US5703089A (en) | Dihydrodibenzisoquinolinediones | |
| JPH0764819B2 (ja) | フエニルキノリン誘導体、その製造法および医薬組成物 | |
| JPH09512539A (ja) | ジヒドロジベンゾ（ｄｅ，ｈ）イソキノリン誘導体および抗癌剤としての該誘導体の使用 | |
| US20050222418A1 (en) | Novel tyloindicines and related processes, pharmaceutical compositions and methods | |
| JP2003525940A (ja) | 抗−腫瘍活性を有する、１，８−ナフタルイミドイミダゾ〔４，５，１−ｄｅ〕アクリドン類 | |
| JPH0733743A (ja) | ２−アリール−４−キノリノール誘導体 | |
| US5641782A (en) | 3-aromatic and 3-heteroaromatic substituted bisnaphthalimides | |
| EP0639183B1 (en) | Nitrogen oxides of aza- and diaza-anthracenedione derivatives, their preparation and their use as antitumor agents | |
| IE49469B1 (en) | Substituted quinazolines | |
| JPH1067750A (ja) | 新規なビスイミド化合物、その製造方法及びそれを含有する医薬組成物 | |
| JPH0676409B2 (ja) | ピラゾロアクリドン誘導体 | |
| JP3145533B2 (ja) | 新規メトトレキセート誘導体 | |
| EP0980372A2 (en) | CYTOTOXIC COMPOUNDS: DERIVATIVES OF THE PYRIDO 2,3,4-$i(kl)] ACRIDINE RING SYSTEM | |
| WO1994005641A1 (en) | 4-SUBSTITUTED 6,9,-BIS (SUBSTITUTED-AMINO) BENZO [g] ISOQUINOLINE-5,10,DIONES | |
| ITMI971850A1 (it) | Derivati di pirazolo-acridine aventi attivita' antitumorale | |
| ITMI971851A1 (it) | Derivati di ammino-acridine carbossiammidi aventi attivita' antitumorale | |
| JPH09208466A (ja) | 縮合多環式ヘテロ環誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20040907 |
|
| A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20050131 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20060117 |