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 them

Info

Publication number: HRP980357A2
Authority: HR; Croatia
Prior art keywords: methyl; bis; indol; benzene; carboxy
Prior art date: 1997-06-25

Application number

HR97110336.1A

Other languages

English (en)

Croatian (hr)

Inventor

Hans Willi Krell

Original Assignee

Hans Willi Krell

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.)

1997-06-25

Filing date

1998-06-24

Publication date

1999-02-28

1998-06-24 Application filed by Hans Willi Krell filed Critical Hans Willi Krell

1999-02-28 Publication of HRP980357A2 publication Critical patent/HRP980357A2/hr

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
238000002560 therapeutic procedure Methods 0.000 description 6
101000990908 Homo sapiens Neutrophil collagenase Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
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STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
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150000003815 prostacyclins Chemical class 0.000 description 1
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)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oncology (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Pyridine Compounds (AREA)

HR97110336.1A 1997-06-25 1998-06-24 Bis-indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them HRP980357A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP97110336A EP0887348A1 (en)	1997-06-25	1997-06-25	Bis-Indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them

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 (xx)
JP (1)	JP2002507206A (xx)
KR (1)	KR20010014215A (xx)
CN (1)	CN1268134A (xx)
AR (1)	AR016283A1 (xx)
AU (1)	AU8629598A (xx)
BR (1)	BR9810947A (xx)
CA (1)	CA2294250A1 (xx)
CO (1)	CO4940464A1 (xx)
HR (1)	HRP980357A2 (xx)
MA (1)	MA26513A1 (xx)
TR (1)	TR199903218T2 (xx)
WO (1)	WO1999000381A1 (xx)
ZA (1)	ZA985482B (xx)

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US6323233B1 (en)	1998-07-08	2001-11-27	Harbor Branch Oceanographic Institution Inc.	Synthetic compounds for treatment of inflammation
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 (en)	2000-11-08	2002-05-16	K.U. Leuven Research & Development	Substituted bis-indole derivatives useful as contrast agents, pharmaceutical compositions containing them and intermediates for producing them
EP1438044A1 (en)	2001-10-19	2004-07-21	Transtech Pharma, Inc.	Bis-heteroaryl alkanes as therapeutic agents
WO2004076386A2 (en)	2003-02-25	2004-09-10	Topotarget Uk Limited	Carbamic acid compounds comprising a bicyclic heteroaryl group as hdac inhibitors
WO2005118539A1 (en)	2004-06-01	2005-12-15	F.Hoffmann-La Roche Ag	3-amino-1-arylpropyl indoles as monoamine reuptake inhibitor
US20060084694A1 (en) *	2004-08-23	2006-04-20	Safe Stephen H	Ligand-dependant activation of Nur77 and uses thereof
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
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
TW200716545A (en) *	2005-06-10	2007-05-01	Sigma Tau Ind Farmaceuti	Indole derivatives having anti-tumor activity
ATE517086T1 (de)	2005-11-30	2011-08-15	Hoffmann La Roche	Verfahren zur synthese von 3-amino-1- arylpropylindolen
RU2008120138A (ru)	2005-11-30	2010-01-10	Ф. Хоффманн-Ля Рош Аг (Ch)	3-амино-1-арилпропилиндолы и аза-замещенные индолы
KR101026570B1 (ko)	2005-11-30	2011-03-31	에프. 호프만-라 로슈 아게	3-아미노-1-아릴프로필 아자인돌 및 이의 용도
CA2750086C (en) *	2009-01-28	2018-01-02	Karus Therapeutics Limited	Scriptaid isosteres and their use in therapy
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 (en)	2011-02-01	2021-07-13	The Board Of Trustees Of The University Of Illinois	4-methyl-n-hydroxybenzamide compounds as histone deacetylase (hdac) inhibitors
CN104797573A (zh)	2012-11-07	2015-07-22	卡鲁斯治疗有限公司	新的组蛋白脱乙酰基酶抑制剂及其在治疗中的用途
WO2014181137A1 (en)	2013-05-10	2014-11-13	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
GB201419264D0 (en)	2014-10-29	2014-12-10	Karus Therapeutics Ltd	Compounds
GB201419228D0 (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
CA3173724A1 (en) *	2020-02-25	2021-09-02	Stephen Safe	Methods for treating endometriosis

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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/en not_active Withdrawn
1998
- 1998-06-19 MA MA25125A patent/MA26513A1/fr unknown
- 1998-06-23 KR KR1019997012300A patent/KR20010014215A/ko not_active Application Discontinuation
- 1998-06-23 AU AU86295/98A patent/AU8629598A/en not_active Abandoned
- 1998-06-23 EP EP98937539A patent/EP0991645A1/en not_active Withdrawn
- 1998-06-23 TR TR1999/03218T patent/TR199903218T2/xx unknown
- 1998-06-23 BR BR9810947-2A patent/BR9810947A/pt not_active Application Discontinuation
- 1998-06-23 CA CA002294250A patent/CA2294250A1/en not_active Abandoned
- 1998-06-23 WO PCT/EP1998/003837 patent/WO1999000381A1/en not_active Application Discontinuation
- 1998-06-23 JP JP50527199A patent/JP2002507206A/ja active Pending
- 1998-06-23 CN CN98808565A patent/CN1268134A/zh active Pending
- 1998-06-24 HR HR97110336.1A patent/HRP980357A2/hr not_active Application Discontinuation
- 1998-06-24 AR ARP980103029A patent/AR016283A1/es unknown
- 1998-06-24 ZA ZA9805482A patent/ZA985482B/xx unknown
- 1998-06-25 CO CO98036361A patent/CO4940464A1/es unknown

Also Published As

Publication number	Publication date
EP0991645A1 (en)	2000-04-12
WO1999000381A1 (en)	1999-01-07
JP2002507206A (ja)	2002-03-05
CA2294250A1 (en)	1999-01-07
AR016283A1 (es)	2001-07-04
MA26513A1 (fr)	2004-12-20
KR20010014215A (ko)	2001-02-26
CO4940464A1 (es)	2000-07-24
TR199903218T2 (xx)	2000-07-21
ZA985482B (en)	1999-12-24
BR9810947A (pt)	2000-09-26
EP0887348A1 (en)	1998-12-30
CN1268134A (zh)	2000-09-27
AU8629598A (en)	1999-01-19

Publication	Publication Date	Title
HRP980357A2 (en)	1999-02-28	Bis-indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them
EP2178870B1 (en)	2018-09-19	Indole and indazole compounds as an inhibitor of cellular necrosis
JP4542783B2 (ja)	2010-09-15	スルホンアミド含有複素環化合物及び血管新生抑制剤とを組み合わせてなる抗腫瘍剤
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