HRP980357A2 - Bis-indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them - Google Patents
Bis-indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing themInfo
- Publication number
- HRP980357A2 HRP980357A2 HR97110336.1A HRP980357A HRP980357A2 HR P980357 A2 HRP980357 A2 HR P980357A2 HR P980357 A HRP980357 A HR P980357A HR P980357 A2 HRP980357 A2 HR P980357A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- bis
- indol
- benzene
- carboxy
- Prior art date
Links
- 230000002001 anti-metastasis Effects 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000000034 method Methods 0.000 title description 13
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 4
- 230000008569 process Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 49
- -1 hydroxy, hydroxymethyl Chemical group 0.000 claims description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229910018828 PO3H2 Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 230000000259 anti-tumor effect Effects 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- ROTWPTVOZDTHBW-UHFFFAOYSA-N 3-[(5-hydroxy-1h-indol-3-yl)-pyridin-3-ylmethyl]-1h-indol-5-ol Chemical compound C12=CC(O)=CC=C2NC=C1C(C=1C2=CC(O)=CC=C2NC=1)C1=CC=CN=C1 ROTWPTVOZDTHBW-UHFFFAOYSA-N 0.000 claims description 4
- SPMXWAZPSFLJAG-UHFFFAOYSA-N 3-[1h-indol-3-yl(pyridin-3-yl)methyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1C(C=1C2=CC=CC=C2NC=1)C1=CC=CN=C1 SPMXWAZPSFLJAG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- MMOQRAOSYPGHLQ-UHFFFAOYSA-N 2-[bis(5-hydroxy-1h-indol-3-yl)methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(C=1C2=CC(O)=CC=C2NC=1)C1=CNC2=CC=C(O)C=C12 MMOQRAOSYPGHLQ-UHFFFAOYSA-N 0.000 claims description 2
- SGDIXEGWNBHWFF-UHFFFAOYSA-N 2-[bis(5-hydroxy-1h-indol-3-yl)methyl]quinolin-8-ol Chemical compound C1=CC=C(O)C2=NC(C(C=3C4=CC(O)=CC=C4NC=3)C3=CNC4=CC=C(C=C43)O)=CC=C21 SGDIXEGWNBHWFF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- HWVSOZHLQBQRHJ-UHFFFAOYSA-N 3,3-bis(2-ethyl-1h-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(C(CC(O)=O)C=3C4=CC=CC=C4NC=3CC)=C(CC)NC2=C1 HWVSOZHLQBQRHJ-UHFFFAOYSA-N 0.000 claims description 2
- SFPKEPNOHMCYKU-UHFFFAOYSA-N 3,3-bis(5-butyl-1h-indol-3-yl)propanoic acid Chemical compound C1=C(CCCC)C=C2C(C(CC(O)=O)C3=CNC4=CC=C(C=C43)CCCC)=CNC2=C1 SFPKEPNOHMCYKU-UHFFFAOYSA-N 0.000 claims description 2
- ZYSBMWCLNSOHNC-UHFFFAOYSA-N 3,3-bis(5-hydroxy-1h-indol-3-yl)propanoic acid Chemical compound C1=C(O)C=C2C(C(C=3C4=CC(O)=CC=C4NC=3)CC(=O)O)=CNC2=C1 ZYSBMWCLNSOHNC-UHFFFAOYSA-N 0.000 claims description 2
- FELGQPKOZDYMIR-UHFFFAOYSA-N 3,3-bis(5-hydroxy-1h-indol-3-yl)propylphosphonic acid Chemical compound C1=C(O)C=C2C(C(CCP(O)(O)=O)C3=CNC4=CC=C(C=C43)O)=CNC2=C1 FELGQPKOZDYMIR-UHFFFAOYSA-N 0.000 claims description 2
- GBJLOJLXAFFDMF-UHFFFAOYSA-N 3,3-bis(6-methylsulfanyl-1h-indol-3-yl)propanoic acid Chemical compound CSC1=CC=C2C(C(CC(O)=O)C=3C4=CC=C(C=C4NC=3)SC)=CNC2=C1 GBJLOJLXAFFDMF-UHFFFAOYSA-N 0.000 claims description 2
- JGUYMUMCMNNZTI-UHFFFAOYSA-N 3-[(2-amino-1h-indol-3-yl)-pyridin-2-ylmethyl]-1h-indol-2-amine Chemical compound NC=1NC2=CC=CC=C2C=1C(C=1C2=CC=CC=C2NC=1N)C1=CC=CC=N1 JGUYMUMCMNNZTI-UHFFFAOYSA-N 0.000 claims description 2
- VHJDRRCDFYETLT-UHFFFAOYSA-N 3-[(5-hydroxy-1h-indol-3-yl)-(2-sulfanylphenyl)methyl]-1h-indol-5-ol Chemical compound C12=CC(O)=CC=C2NC=C1C(C=1C2=CC(O)=CC=C2NC=1)C1=CC=CC=C1S VHJDRRCDFYETLT-UHFFFAOYSA-N 0.000 claims description 2
- ZKCZOWLZPFTDTG-UHFFFAOYSA-N 3-[(5-hydroxy-1h-indol-3-yl)-quinolin-2-ylmethyl]-1h-indol-5-ol Chemical compound C1=CC=CC2=NC(C(C=3C4=CC(O)=CC=C4NC=3)C3=CNC4=CC=C(C=C43)O)=CC=C21 ZKCZOWLZPFTDTG-UHFFFAOYSA-N 0.000 claims description 2
- MYUBONKXBUBANG-UHFFFAOYSA-N 3-[(5-methylfuran-2-yl)-(5-sulfanyl-1h-indol-3-yl)methyl]-1h-indole-5-thiol Chemical compound O1C(C)=CC=C1C(C=1C2=CC(S)=CC=C2NC=1)C1=CNC2=CC=C(S)C=C12 MYUBONKXBUBANG-UHFFFAOYSA-N 0.000 claims description 2
- JANIXKORCLKFEU-UHFFFAOYSA-N 3-[1h-imidazol-2-yl(1h-indol-3-yl)methyl]-1h-indole Chemical compound C1=CNC(C(C=2C3=CC=CC=C3NC=2)C=2C3=CC=CC=C3NC=2)=N1 JANIXKORCLKFEU-UHFFFAOYSA-N 0.000 claims description 2
- PVSJNTALMOTREX-UHFFFAOYSA-N 3-[1h-imidazol-2-yl-(2-propan-2-yl-1h-indol-3-yl)methyl]-2-propan-2-yl-1h-indole Chemical compound CC(C)C=1NC2=CC=CC=C2C=1C(C=1C2=CC=CC=C2NC=1C(C)C)C1=NC=CN1 PVSJNTALMOTREX-UHFFFAOYSA-N 0.000 claims description 2
- VQWZIPRNTRIIKA-UHFFFAOYSA-N 3-[1h-indol-3-yl-(5-methylfuran-2-yl)methyl]-1h-indole Chemical compound O1C(C)=CC=C1C(C=1C2=CC=CC=C2NC=1)C1=CNC2=CC=CC=C12 VQWZIPRNTRIIKA-UHFFFAOYSA-N 0.000 claims description 2
- BQCPGUWRRVIZPU-UHFFFAOYSA-N 3-[1h-indol-3-yl-(6-pyridin-2-ylpyridin-3-yl)methyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1C(C=1C2=CC=CC=C2NC=1)C(C=N1)=CC=C1C1=CC=CC=N1 BQCPGUWRRVIZPU-UHFFFAOYSA-N 0.000 claims description 2
- AQMYNEBCPSMUOR-UHFFFAOYSA-N 3-[3-amino-1-(5-hydroxy-1h-indol-3-yl)propyl]-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(C(C=3C4=CC(O)=CC=C4NC=3)CCN)=CNC2=C1 AQMYNEBCPSMUOR-UHFFFAOYSA-N 0.000 claims description 2
- VZBCPQZENJXEFQ-UHFFFAOYSA-N 3-[bis(1h-indol-3-yl)methyl]-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC(C(C=2C3=CC=CC=C3NC=2)C=2C3=CC=CC=C3NC=2)=C1 VZBCPQZENJXEFQ-UHFFFAOYSA-N 0.000 claims description 2
- MGCSYMDFXDNXBE-UHFFFAOYSA-N 3-[bis(1h-indol-3-yl)methyl]benzene-1,2-diol Chemical compound OC1=CC=CC(C(C=2C3=CC=CC=C3NC=2)C=2C3=CC=CC=C3NC=2)=C1O MGCSYMDFXDNXBE-UHFFFAOYSA-N 0.000 claims description 2
- VKCTUWGLBAAHPL-UHFFFAOYSA-N 3-[bis(2-hydroxy-1h-indol-3-yl)methyl]benzene-1,2-diol Chemical compound OC=1NC2=CC=CC=C2C=1C(C=1C2=CC=CC=C2NC=1O)C1=CC=CC(O)=C1O VKCTUWGLBAAHPL-UHFFFAOYSA-N 0.000 claims description 2
- UTERKXARGODRDL-UHFFFAOYSA-N 3-[bis(2-methyl-1h-indol-3-yl)methyl]quinoline Chemical compound C1=CC=CC2=CC(C(C=3C4=CC=CC=C4NC=3C)C=3C4=CC=CC=C4NC=3C)=CN=C21 UTERKXARGODRDL-UHFFFAOYSA-N 0.000 claims description 2
- VNCNBHVAIXCQEN-UHFFFAOYSA-N 3-[bis(6-ethylsulfanyl-1h-indol-3-yl)methyl]benzoic acid Chemical compound C=1NC2=CC(SCC)=CC=C2C=1C(C=1C2=CC=C(SCC)C=C2NC=1)C1=CC=CC(C(O)=O)=C1 VNCNBHVAIXCQEN-UHFFFAOYSA-N 0.000 claims description 2
- YVFOVABQXGPMOK-UHFFFAOYSA-N 3-[bis[6-(diethylamino)-1h-indol-3-yl]methyl]benzene-1,2-diol Chemical compound C=1NC2=CC(N(CC)CC)=CC=C2C=1C(C=1C2=CC=C(C=C2NC=1)N(CC)CC)C1=CC=CC(O)=C1O YVFOVABQXGPMOK-UHFFFAOYSA-N 0.000 claims description 2
- FYLVVGIPRDNWHG-UHFFFAOYSA-N 3-[furan-2-yl-(5-hydroxy-1h-indol-3-yl)methyl]-1h-indol-5-ol Chemical compound C12=CC(O)=CC=C2NC=C1C(C=1C2=CC(O)=CC=C2NC=1)C1=CC=CO1 FYLVVGIPRDNWHG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- IFMKPGPGNRHHDO-UHFFFAOYSA-N 4,4-bis(1h-indol-3-yl)butane-1-thiol Chemical compound C1=CC=C2C(C(C=3C4=CC=CC=C4NC=3)CCCS)=CNC2=C1 IFMKPGPGNRHHDO-UHFFFAOYSA-N 0.000 claims description 2
- LFWXMAFQHHQECL-UHFFFAOYSA-N 4,4-bis(6-ethyl-1h-indol-3-yl)butan-1-amine Chemical compound CCC1=CC=C2C(C(CCCN)C=3C4=CC=C(C=C4NC=3)CC)=CNC2=C1 LFWXMAFQHHQECL-UHFFFAOYSA-N 0.000 claims description 2
- PSHZFRNSCVAEJZ-UHFFFAOYSA-N 4,4-bis(6-methoxy-1h-indol-3-yl)butanoic acid Chemical compound COC1=CC=C2C(C(CCC(O)=O)C=3C4=CC=C(C=C4NC=3)OC)=CNC2=C1 PSHZFRNSCVAEJZ-UHFFFAOYSA-N 0.000 claims description 2
- OTXDTWXEFXVSFA-UHFFFAOYSA-N 4-[bis(5-bromo-1h-indol-3-yl)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C=1C2=CC(Br)=CC=C2NC=1)C1=CNC2=CC=C(Br)C=C12 OTXDTWXEFXVSFA-UHFFFAOYSA-N 0.000 claims description 2
- ZALZWCJXBOZPRO-UHFFFAOYSA-N 4-[bis(5-methoxy-1h-indol-3-yl)methyl]isoquinoline Chemical compound C1=CC=C2C(C(C=3C4=CC(OC)=CC=C4NC=3)C3=CNC4=CC=C(C=C43)OC)=CN=CC2=C1 ZALZWCJXBOZPRO-UHFFFAOYSA-N 0.000 claims description 2
- LHGHGSUAKKRTNX-UHFFFAOYSA-N 4-[bis(5-propan-2-yl-1h-indol-3-yl)methyl]benzene-1,2-diol Chemical compound C12=CC(C(C)C)=CC=C2NC=C1C(C=1C2=CC(=CC=C2NC=1)C(C)C)C1=CC=C(O)C(O)=C1 LHGHGSUAKKRTNX-UHFFFAOYSA-N 0.000 claims description 2
- UPGDFHKCMBZQGS-UHFFFAOYSA-N 4-[bis[6-(methylamino)-1h-indol-3-yl]methyl]benzene-1,2-diol Chemical compound C=1NC2=CC(NC)=CC=C2C=1C(C=1C2=CC=C(NC)C=C2NC=1)C1=CC=C(O)C(O)=C1 UPGDFHKCMBZQGS-UHFFFAOYSA-N 0.000 claims description 2
- BXJVSNWWJWQPBL-UHFFFAOYSA-N 5-[bis(1h-indol-3-yl)methyl]-2-hydroxybenzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C(C=2C3=CC=CC=C3NC=2)C=2C3=CC=CC=C3NC=2)=C1 BXJVSNWWJWQPBL-UHFFFAOYSA-N 0.000 claims description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
- LAOGUDMOCKJKCY-UHFFFAOYSA-N 5-fluoro-3-[(5-fluoro-1h-indol-3-yl)-(1h-imidazol-2-yl)methyl]-1h-indole Chemical compound C12=CC(F)=CC=C2NC=C1C(C=1C2=CC(F)=CC=C2NC=1)C1=NC=CN1 LAOGUDMOCKJKCY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- WZLUMQFXJDMNPE-UHFFFAOYSA-N 6-chloro-3-[(6-chloro-1h-indol-3-yl)-(1h-pyrrol-3-yl)methyl]-1h-indole Chemical compound C=1NC2=CC(Cl)=CC=C2C=1C(C=1C2=CC=C(Cl)C=C2NC=1)C=1C=CNC=1 WZLUMQFXJDMNPE-UHFFFAOYSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- QSMGNJZGMRGROP-UHFFFAOYSA-N 8-[bis(5-methyl-1h-indol-3-yl)methyl]quinoline Chemical compound C1=CN=C2C(C(C=3C4=CC(C)=CC=C4NC=3)C3=CNC4=CC=C(C=C43)C)=CC=CC2=C1 QSMGNJZGMRGROP-UHFFFAOYSA-N 0.000 claims description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- KYUAOMVMIHZVNP-UHFFFAOYSA-N [3-[[2-(hydroxymethyl)-1h-indol-3-yl]-isoquinolin-1-ylmethyl]-1h-indol-2-yl]methanol Chemical compound C1=CC=C2C(C(C=3C4=CC=CC=C4NC=3CO)C=3C4=CC=CC=C4NC=3CO)=NC=CC2=C1 KYUAOMVMIHZVNP-UHFFFAOYSA-N 0.000 claims description 2
- UQWXWBGWWPFYDH-UHFFFAOYSA-N [3-[bis(5-iodo-1h-indol-3-yl)methyl]phenyl]phosphonic acid Chemical compound OP(O)(=O)C1=CC=CC(C(C=2C3=CC(I)=CC=C3NC=2)C=2C3=CC(I)=CC=C3NC=2)=C1 UQWXWBGWWPFYDH-UHFFFAOYSA-N 0.000 claims description 2
- ZFAOOUUHZKMPSL-UHFFFAOYSA-N [5-[bis(1h-indol-3-yl)methyl]furan-2-yl]methanol Chemical compound O1C(CO)=CC=C1C(C=1C2=CC=CC=C2NC=1)C1=CNC2=CC=CC=C12 ZFAOOUUHZKMPSL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- MVMDVZUZLMFWNP-UHFFFAOYSA-N ethyl 3-[3-(dimethylamino)-1-(5-ethoxycarbonyl-1h-indol-3-yl)propyl]-1h-indole-5-carboxylate Chemical compound C1=C(C(=O)OCC)C=C2C(C(CCN(C)C)C3=CNC4=CC=C(C=C43)C(=O)OCC)=CNC2=C1 MVMDVZUZLMFWNP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- ZBUIUZRMMDVIJR-UHFFFAOYSA-N methyl 4-[bis(5-amino-1h-indol-3-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C=1C2=CC(N)=CC=C2NC=1)C1=CNC2=CC=C(N)C=C12 ZBUIUZRMMDVIJR-UHFFFAOYSA-N 0.000 claims description 2
- OPVZSFPTYCUGCF-UHFFFAOYSA-N n-hydroxy-3,3-bis(1h-indol-3-yl)propanamide Chemical compound C1=CC=C2C(C(C=3C4=CC=CC=C4NC=3)CC(=O)NO)=CNC2=C1 OPVZSFPTYCUGCF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- FALCCBVEPDBPGU-UHFFFAOYSA-N [3-[(6-acetyloxy-1h-indol-3-yl)-thiophen-2-ylmethyl]-1h-indol-6-yl] acetate Chemical compound C=1NC2=CC(OC(=O)C)=CC=C2C=1C(C=1C2=CC=C(OC(C)=O)C=C2NC=1)C1=CC=CS1 FALCCBVEPDBPGU-UHFFFAOYSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 206010027476 Metastases Diseases 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 7
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 230000009401 metastasis Effects 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
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- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97110336A EP0887348A1 (fr) | 1997-06-25 | 1997-06-25 | Dérivés de bisindole ayant une activité antimétastatique, leur procédé de préparation et compositions pharmaceutiques les contenant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP980357A2 true HRP980357A2 (en) | 1999-02-28 |
Family
ID=8226954
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR97110336.1A HRP980357A2 (en) | 1997-06-25 | 1998-06-24 | Bis-indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP0887348A1 (fr) |
| JP (1) | JP2002507206A (fr) |
| KR (1) | KR20010014215A (fr) |
| CN (1) | CN1268134A (fr) |
| AR (1) | AR016283A1 (fr) |
| AU (1) | AU8629598A (fr) |
| BR (1) | BR9810947A (fr) |
| CA (1) | CA2294250A1 (fr) |
| CO (1) | CO4940464A1 (fr) |
| HR (1) | HRP980357A2 (fr) |
| MA (1) | MA26513A1 (fr) |
| TR (1) | TR199903218T2 (fr) |
| WO (1) | WO1999000381A1 (fr) |
| ZA (1) | ZA985482B (fr) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE277010T1 (de) | 1998-07-08 | 2004-10-15 | Harbor Branch Oceanographic | Bis-indolederivate und ihre verwendung als entzündungshemmende mittel |
| US7709520B2 (en) * | 2000-10-06 | 2010-05-04 | The Texas A&M University System | Diindolylmethane and C-substituted diindolylmethane compositions and methods for the treatment of multiple cancers |
| IT1317925B1 (it) | 2000-11-03 | 2003-07-15 | Sigma Tau Ind Farmaceuti | Bis-eterocicli ad attivita' antitumorale e chemosensibilizzante. |
| GB2368843A (en) * | 2000-11-08 | 2002-05-15 | Leuven K U Res & Dev | Non-porphyrin multipurpose contrast agents |
| WO2002038546A1 (fr) | 2000-11-08 | 2002-05-16 | K.U. Leuven Research & Development | Derives de bis-indole substitue utilises comme agents de contraste, compositions pharmaceutiques contenant lesdits derives et intermediaires permettant de preparer ces derives |
| JP2005508355A (ja) | 2001-10-19 | 2005-03-31 | トランス テック ファーマ，インコーポレイテッド | 治療薬としてのビス−ヘテロアリールアルカン |
| WO2004076386A2 (fr) | 2003-02-25 | 2004-09-10 | Topotarget Uk Limited | Composes d'acide carbamique comprenant un groupe heteroaryle bicyclique utilises en tant qu'inhibiteurs de hdac |
| CA2569238A1 (fr) | 2004-06-01 | 2005-12-15 | F. Hoffmann-La Roche Ag | Inhibiteur du recaptage des monoamines |
| EP1793820A2 (fr) * | 2004-08-23 | 2007-06-13 | The Texas A & M University System | Activation dependant des ligands de nur77 et ses applications |
| CN1332948C (zh) * | 2005-05-12 | 2007-08-22 | 苏州大学 | 双吲哚烷基衍生物的合成方法 |
| CN100412058C (zh) * | 2005-05-12 | 2008-08-20 | 苏州大学 | 一种双吲哚烷基化合物的合成方法 |
| TW200716545A (en) * | 2005-06-10 | 2007-05-01 | Sigma Tau Ind Farmaceuti | Indole derivatives having anti-tumor activity |
| WO2007062996A1 (fr) | 2005-11-30 | 2007-06-07 | F. Hoffmann-La Roche Ag | 3-amino-1-arylpropyl indoles et indoles a substitution azo |
| AU2006319229B2 (en) | 2005-11-30 | 2011-09-15 | F. Hoffmann-La Roche Ag | Methods for synthesis of 3-amino-1-arylpropyl indoles |
| RU2008120141A (ru) | 2005-11-30 | 2010-01-10 | Ф. Хоффманн-Ля Рош Аг (Ch) | 3-амино-2-арилпропилазаиндолы и их применения |
| ES2650810T3 (es) | 2009-01-28 | 2018-01-22 | Karus Therapeutics Limited | Isósteros de Scriptaid y su uso en terapia |
| CN101585800B (zh) * | 2009-06-19 | 2011-06-15 | 中国科学院上海有机化学研究所 | 具有生物活性双吲哚甲烷类化合物 |
| CA2825599C (fr) | 2011-02-01 | 2021-07-13 | The Board Of Trustees Of The University Of Illinois | Composes 4-methyl-n-hydroxybenzamide comme inhibiteurs d'histone deacetylase (hdac) |
| EP2917202B1 (fr) * | 2012-11-07 | 2018-05-02 | Karus Therapeutics Limited | Nouveaux inhibiteurs d'histone déacétylase et leur utilisation en thérapie |
| AU2014264370B2 (en) | 2013-05-10 | 2017-12-14 | Karus Therapeutics Ltd | Novel histone deacetylase inhibitors |
| CN103274987A (zh) * | 2013-06-07 | 2013-09-04 | 华东师范大学 | 3,3-二取代氧化吲哚衍生物及其合成方法和应用 |
| CN104030964B (zh) * | 2014-06-05 | 2016-06-29 | 天津科技大学 | 双吲哚类化合物及合成方法 |
| GB201419228D0 (en) | 2014-10-29 | 2014-12-10 | Karus Therapeutics Ltd | Compounds |
| GB201419264D0 (en) | 2014-10-29 | 2014-12-10 | Karus Therapeutics Ltd | Compounds |
| CN107698658B (zh) * | 2015-06-23 | 2021-02-12 | 首都医科大学 | 双[3-(乙酰-Lys-AA-OBzl)-吲哚-2-基]乙烷,其制备,活性和应用 |
| JP2020530477A (ja) * | 2017-08-10 | 2020-10-22 | ザ テキサス エーアンドエム ユニヴァーシティ システム | Ｎｒ４ａ１リガンド、医薬組成物、及び関連する使用方法 |
| US20210401803A1 (en) * | 2018-11-21 | 2021-12-30 | The University Of The West Indies | Compounds and uses thereof |
| US20230113363A1 (en) * | 2020-02-25 | 2023-04-13 | The Texas A&M University System | Methods for treating endometriosis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4866084A (en) * | 1987-07-17 | 1989-09-12 | Harbor Branch Oceanographic Institution, Inc. | Topsentin compounds effective against viruses and certain tumors |
| US5380746A (en) * | 1989-05-05 | 1995-01-10 | Goedecke Aktiengesellschaft | Bis-(1H-indol-3-YL)-maleinimide derivatives, processes for the preparation thereof and pharmaceutical compositions containing them |
| GB9516943D0 (en) * | 1995-08-18 | 1995-10-18 | Cancer Soc Auckland Div Nz Inc | Novel cyclopropylindoles and their secoprecursors,and their use as prodrugs |
-
1997
- 1997-06-25 EP EP97110336A patent/EP0887348A1/fr not_active Withdrawn
-
1998
- 1998-06-19 MA MA25125A patent/MA26513A1/fr unknown
- 1998-06-23 CN CN98808565A patent/CN1268134A/zh active Pending
- 1998-06-23 CA CA002294250A patent/CA2294250A1/fr not_active Abandoned
- 1998-06-23 TR TR1999/03218T patent/TR199903218T2/xx unknown
- 1998-06-23 JP JP50527199A patent/JP2002507206A/ja active Pending
- 1998-06-23 WO PCT/EP1998/003837 patent/WO1999000381A1/fr not_active Application Discontinuation
- 1998-06-23 AU AU86295/98A patent/AU8629598A/en not_active Abandoned
- 1998-06-23 EP EP98937539A patent/EP0991645A1/fr not_active Withdrawn
- 1998-06-23 BR BR9810947-2A patent/BR9810947A/pt not_active Application Discontinuation
- 1998-06-23 KR KR1019997012300A patent/KR20010014215A/ko not_active Application Discontinuation
- 1998-06-24 ZA ZA9805482A patent/ZA985482B/xx unknown
- 1998-06-24 HR HR97110336.1A patent/HRP980357A2/hr not_active Application Discontinuation
- 1998-06-24 AR ARP980103029A patent/AR016283A1/es unknown
- 1998-06-25 CO CO98036361A patent/CO4940464A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1268134A (zh) | 2000-09-27 |
| WO1999000381A1 (fr) | 1999-01-07 |
| MA26513A1 (fr) | 2004-12-20 |
| ZA985482B (en) | 1999-12-24 |
| CO4940464A1 (es) | 2000-07-24 |
| TR199903218T2 (xx) | 2000-07-21 |
| EP0887348A1 (fr) | 1998-12-30 |
| AR016283A1 (es) | 2001-07-04 |
| BR9810947A (pt) | 2000-09-26 |
| KR20010014215A (ko) | 2001-02-26 |
| CA2294250A1 (fr) | 1999-01-07 |
| EP0991645A1 (fr) | 2000-04-12 |
| JP2002507206A (ja) | 2002-03-05 |
| AU8629598A (en) | 1999-01-19 |
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| A1OB | Publication of a patent application | ||
| OBST | Application withdrawn |