HRP20050092A2 - Arylcarbonylpiperazines and heteroarylcarbonylpiperazines and the use thereof for treating benign and malignant tumour diseases - Google Patents
Arylcarbonylpiperazines and heteroarylcarbonylpiperazines and the use thereof for treating benign and malignant tumour diseasesInfo
- Publication number
- HRP20050092A2 HRP20050092A2 HR20050092A HRP20050092A HRP20050092A2 HR P20050092 A2 HRP20050092 A2 HR P20050092A2 HR 20050092 A HR20050092 A HR 20050092A HR P20050092 A HRP20050092 A HR P20050092A HR P20050092 A2 HRP20050092 A2 HR P20050092A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- alkylaryl
- cycloalkyl
- Prior art date
Links
- 201000011510 cancer Diseases 0.000 title claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 71
- -1 piperazinylcarbonyl compound Chemical class 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- FLJXVTOBZRZASY-UHFFFAOYSA-N 4-[4-(3,5-dimethoxyphenyl)piperazine-1-carbonyl]fluoren-9-one Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C=2C=3C4=CC=CC=C4C(=O)C=3C=CC=2)=C1 FLJXVTOBZRZASY-UHFFFAOYSA-N 0.000 claims description 11
- KNWDPIZVPTUPHH-UHFFFAOYSA-N 4-[4-(3-hydroxyphenyl)piperazine-1-carbonyl]fluoren-9-one Chemical compound OC1=CC=CC(N2CCN(CC2)C(=O)C=2C=3C4=CC=CC=C4C(=O)C=3C=CC=2)=C1 KNWDPIZVPTUPHH-UHFFFAOYSA-N 0.000 claims description 11
- ZWSVKIGYVMGZLZ-UHFFFAOYSA-N 4-[4-(6-methylpyridin-2-yl)piperazine-1-carbonyl]fluoren-9-one Chemical compound CC1=CC=CC(N2CCN(CC2)C(=O)C=2C=3C4=CC=CC=C4C(=O)C=3C=CC=2)=N1 ZWSVKIGYVMGZLZ-UHFFFAOYSA-N 0.000 claims description 11
- WVHQWDYVYJYULM-UHFFFAOYSA-N 9h-fluoren-1-yl-[4-(3-methoxyphenyl)piperazin-1-yl]methanone Chemical compound COC1=CC=CC(N2CCN(CC2)C(=O)C=2C3=C(C4=CC=CC=C4C3)C=CC=2)=C1 WVHQWDYVYJYULM-UHFFFAOYSA-N 0.000 claims description 11
- VLKUJWHFKPKFRE-UHFFFAOYSA-N 9h-fluoren-9-yl-[4-(3-methoxyphenyl)piperazin-1-yl]methanone Chemical compound COC1=CC=CC(N2CCN(CC2)C(=O)C2C3=CC=CC=C3C3=CC=CC=C32)=C1 VLKUJWHFKPKFRE-UHFFFAOYSA-N 0.000 claims description 11
- GFHYHAMWWWMKJT-UHFFFAOYSA-N [4-(3,5-dimethoxyphenyl)piperazin-1-yl]-(5-methyl-3-phenyl-1,2-oxazol-4-yl)methanone Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C=2C(=NOC=2C)C=2C=CC=CC=2)=C1 GFHYHAMWWWMKJT-UHFFFAOYSA-N 0.000 claims description 11
- QKMMPAFFBHMRBL-UHFFFAOYSA-N [4-(3,5-dimethoxyphenyl)piperazin-1-yl]-(9h-fluoren-1-yl)methanone Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C=2C3=C(C4=CC=CC=C4C3)C=CC=2)=C1 QKMMPAFFBHMRBL-UHFFFAOYSA-N 0.000 claims description 11
- IRERFHPAZVTLNH-UHFFFAOYSA-N [4-(3,5-dimethoxyphenyl)piperazin-1-yl]-(9h-xanthen-9-yl)methanone Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C2C3=CC=CC=C3OC3=CC=CC=C32)=C1 IRERFHPAZVTLNH-UHFFFAOYSA-N 0.000 claims description 11
- MFTWLTJZAORBOY-UHFFFAOYSA-N [4-(3,5-dimethoxyphenyl)piperazin-1-yl]-[1-(4-nitrophenyl)-5-(trifluoromethyl)pyrazol-4-yl]methanone Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C2=C(N(N=C2)C=2C=CC(=CC=2)[N+]([O-])=O)C(F)(F)F)=C1 MFTWLTJZAORBOY-UHFFFAOYSA-N 0.000 claims description 11
- MIQGQNUVNMLISU-UHFFFAOYSA-N [4-(3-hydroxyphenyl)piperazin-1-yl]-(2-phenylpyrazol-3-yl)methanone Chemical compound OC1=CC=CC(N2CCN(CC2)C(=O)C=2N(N=CC=2)C=2C=CC=CC=2)=C1 MIQGQNUVNMLISU-UHFFFAOYSA-N 0.000 claims description 11
- PGBCNRJBTPSOKW-UHFFFAOYSA-N [4-(3-methoxyphenyl)piperazin-1-yl]-(2-phenylpyrazol-3-yl)methanone Chemical compound COC1=CC=CC(N2CCN(CC2)C(=O)C=2N(N=CC=2)C=2C=CC=CC=2)=C1 PGBCNRJBTPSOKW-UHFFFAOYSA-N 0.000 claims description 11
- NQQRHAGTVYKGPN-UHFFFAOYSA-N [4-(3-methoxyphenyl)piperazin-1-yl]-(9h-xanthen-9-yl)methanone Chemical compound COC1=CC=CC(N2CCN(CC2)C(=O)C2C3=CC=CC=C3OC3=CC=CC=C32)=C1 NQQRHAGTVYKGPN-UHFFFAOYSA-N 0.000 claims description 11
- WKPLMFYVYLQMPS-UHFFFAOYSA-N [4-(6-methylpyridin-2-yl)piperazin-1-yl]-(2-phenylpyrazol-3-yl)methanone Chemical compound CC1=CC=CC(N2CCN(CC2)C(=O)C=2N(N=CC=2)C=2C=CC=CC=2)=N1 WKPLMFYVYLQMPS-UHFFFAOYSA-N 0.000 claims description 11
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 150000003254 radicals Chemical class 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- BSFGOBABAPXFGY-UHFFFAOYSA-N [3,5-bis(methylsulfanyl)-1,2-thiazol-4-yl]-[4-(6-methylpyridin-2-yl)piperazin-1-yl]methanone Chemical compound CSC1=NSC(SC)=C1C(=O)N1CCN(C=2N=C(C)C=CC=2)CC1 BSFGOBABAPXFGY-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- XXISHMRKDDBJJA-UHFFFAOYSA-N [4-(3,5-dimethoxyphenyl)piperazin-1-yl]-isoquinolin-1-ylmethanone Chemical compound COC1=CC(OC)=CC(N2CCN(CC2)C(=O)C=2C3=CC=CC=C3C=CN=2)=C1 XXISHMRKDDBJJA-UHFFFAOYSA-N 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000003367 polycyclic group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 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 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 4
- 229910006069 SO3H Inorganic materials 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 125000006519 CCH3 Chemical group 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical group [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000002015 acyclic group Chemical group 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 2
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002390 heteroarenes Chemical class 0.000 claims description 2
- 125000006038 hexenyl group Chemical group 0.000 claims description 2
- 125000005980 hexynyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 229910001437 manganese ion Inorganic materials 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 claims description 2
- 125000006194 pentinyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 claims description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004306 triazinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 4
- 239000000654 additive Substances 0.000 claims 2
- 238000006386 neutralization reaction Methods 0.000 claims 2
- 239000003981 vehicle Substances 0.000 claims 2
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims 1
- 150000007514 bases Chemical class 0.000 claims 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 25
- 239000000126 substance Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 238000012360 testing method Methods 0.000 description 14
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 11
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- 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
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/02—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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
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)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39302702P | 2002-06-29 | 2002-06-29 | |
| PCT/EP2003/006555 WO2004002965A1 (de) | 2002-06-29 | 2003-06-20 | Aryl- und heteroarylcarbonylpiperazine und deren verwendung zur behandlung gutartiger und bösartiger tumorerkrankungen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20050092A2 true HRP20050092A2 (en) | 2005-02-28 |
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| HR20050092A HRP20050092A2 (en) | 2002-06-29 | 2005-01-27 | Arylcarbonylpiperazines and heteroarylcarbonylpiperazines and the use thereof for treating benign and malignant tumour diseases |
Country Status (18)
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| US (1) | US20040097734A1 (es) |
| EP (1) | EP1517898A1 (es) |
| JP (1) | JP2005538968A (es) |
| CN (1) | CN100509790C (es) |
| AR (1) | AR040315A1 (es) |
| AU (1) | AU2003246571B2 (es) |
| BR (1) | BR0312294A (es) |
| CA (1) | CA2433983A1 (es) |
| HK (1) | HK1080840A1 (es) |
| HR (1) | HRP20050092A2 (es) |
| MX (1) | MXPA04012959A (es) |
| NO (1) | NO20050428L (es) |
| NZ (1) | NZ537916A (es) |
| PL (1) | PL375527A1 (es) |
| RU (1) | RU2335496C2 (es) |
| UA (1) | UA79286C2 (es) |
| WO (1) | WO2004002965A1 (es) |
| ZA (1) | ZA200409610B (es) |
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| EP1590329A1 (fr) * | 2003-01-28 | 2005-11-02 | Aventis Pharma S.A. | Produits n-aryl-heteroaromatiques, compositions les contenant et utilisation |
| EP1620405A2 (en) * | 2003-05-01 | 2006-02-01 | Abbott Laboratories | Pyrazole-amides and sulfonamides as sodium channel modulators |
| AR044586A1 (es) * | 2003-06-04 | 2005-09-21 | Aventis Pharma Sa | Productos aril - heteroaromaticos, composiciones que los contienen y su utilizacion |
| FR2855825B1 (fr) * | 2003-06-04 | 2008-08-22 | Aventis Pharma Sa | Produits aryl-heteroaromatiques, compositions les contenant et utilisation |
| EP1645556A1 (en) * | 2004-10-07 | 2006-04-12 | Boehringer Ingelheim International GmbH | Arylpiperazine-benzoylamide derivatives useful as pharmaceutical agents |
| JP5149177B2 (ja) | 2005-07-25 | 2013-02-20 | シンタ ファーマシューティカルズ コーポレーション | 増殖性疾患の治療のための、チューブリンポリマー化の１，２，３−トリアゾール系抑制剤 |
| AU2007275301A1 (en) * | 2006-07-20 | 2008-01-24 | Amgen Inc. | Substituted azole aromatic heterocycles as inhibitors of 11-beta-HSD-1 |
| KR100932093B1 (ko) | 2006-09-27 | 2009-12-16 | 주식회사종근당 | 미세소관 형성 저해제로서 유용한 벤조페논 유도체 |
| RU2454412C2 (ru) * | 2007-08-13 | 2012-06-27 | Ф.Хоффманн-Ля Рош Аг | Новые пиперазинамидные производные |
| CN101597278B (zh) | 2008-06-04 | 2013-04-17 | 中国中化股份有限公司 | 酰胺类化合物及其制备与应用 |
| US9212177B2 (en) * | 2009-08-05 | 2015-12-15 | Versitech Limited | Antiviral compounds and methods of making and using thereof |
| US20120149715A1 (en) * | 2010-05-28 | 2012-06-14 | Yi Tsun Richard Kao | Compounds and methods for the treatment of viral infections |
| KR101369584B1 (ko) | 2011-04-19 | 2014-03-06 | 일양약품주식회사 | 페닐-이속사졸 유도체 및 그의 제조방법 |
| AU2017311691B2 (en) * | 2016-08-18 | 2021-12-02 | Vidac Pharma Ltd. | Piperazine derivatives, pharmaceutical compositions and methods of use thereof |
| US10682346B2 (en) | 2016-11-07 | 2020-06-16 | Vidac Pharma Ltd. | Use of hexokinase 2/mitochondria-detaching compounds for activating immune responses |
| US11266639B2 (en) | 2016-11-07 | 2022-03-08 | Vidac Pharma Ltd. | Use of hexokinase 2/mitochondria-detaching compounds for treating hexokinase-2 (HK2)-expressing cancers |
| RU2700576C1 (ru) * | 2019-05-07 | 2019-09-18 | Федеральное государственное бюджетное научное учреждение "Институт экспериментальной медицины" (ФГБНУ "ИЭМ") | Анксиолитическое средство |
| CN111303132B (zh) * | 2020-03-19 | 2023-05-23 | 辽宁孚音生物科技有限公司 | 一种抗癌化合物及其制备方法和应用 |
| KR20230043222A (ko) * | 2020-08-12 | 2023-03-30 | 스프루스 바이오사이언시스 인코포레이티드 | 다낭성 난소 증후군을 치료하기 위한 방법 및 조성물 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DE1620016C3 (de) * | 1966-07-02 | 1979-08-30 | Merck Patent Gmbh, 6100 Darmstadt | 3-{Piperazinoalkyl)-pyrazole und Verfahren zu ihrer Herstellung |
| US3468882A (en) * | 1966-10-07 | 1969-09-23 | Sterling Drug Inc | Phenylhydrazone derivatives as intermediates for preparing indoles |
| BE791501A (fr) * | 1971-11-19 | 1973-05-17 | Albert Ag Chem Werke | Diamines cycliques n,n'-disubstituees et leur procede de preparation |
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- 2003-06-20 WO PCT/EP2003/006555 patent/WO2004002965A1/de active IP Right Grant
- 2003-06-20 MX MXPA04012959A patent/MXPA04012959A/es active IP Right Grant
- 2003-06-20 EP EP03761482A patent/EP1517898A1/de not_active Withdrawn
- 2003-06-20 BR BR0312294-8A patent/BR0312294A/pt not_active IP Right Cessation
- 2003-06-20 JP JP2004516632A patent/JP2005538968A/ja active Pending
- 2003-06-20 CN CNB038154854A patent/CN100509790C/zh not_active Expired - Fee Related
- 2003-06-20 AU AU2003246571A patent/AU2003246571B2/en not_active Ceased
- 2003-06-20 UA UA20041210297A patent/UA79286C2/uk unknown
- 2003-06-20 NZ NZ537916A patent/NZ537916A/en unknown
- 2003-06-20 RU RU2005102478/04A patent/RU2335496C2/ru not_active IP Right Cessation
- 2003-06-20 PL PL03375527A patent/PL375527A1/xx not_active Application Discontinuation
- 2003-06-27 AR ARP030102359A patent/AR040315A1/es unknown
- 2003-06-27 CA CA002433983A patent/CA2433983A1/en not_active Abandoned
- 2003-06-27 US US10/608,520 patent/US20040097734A1/en not_active Abandoned
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2004
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- 2005-01-25 NO NO20050428A patent/NO20050428L/no not_active Application Discontinuation
- 2005-01-27 HR HR20050092A patent/HRP20050092A2/hr not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2003246571B2 (en) | 2008-06-26 |
| US20040097734A1 (en) | 2004-05-20 |
| RU2335496C2 (ru) | 2008-10-10 |
| EP1517898A1 (de) | 2005-03-30 |
| HK1080840A1 (en) | 2006-05-04 |
| PL375527A1 (en) | 2005-11-28 |
| MXPA04012959A (es) | 2005-05-16 |
| ZA200409610B (en) | 2005-05-25 |
| CN100509790C (zh) | 2009-07-08 |
| AR040315A1 (es) | 2005-03-23 |
| AU2003246571A1 (en) | 2004-01-19 |
| BR0312294A (pt) | 2005-04-12 |
| NZ537916A (en) | 2005-11-25 |
| NO20050428L (no) | 2005-01-25 |
| WO2004002965A1 (de) | 2004-01-08 |
| UA79286C2 (en) | 2007-06-11 |
| CN1665792A (zh) | 2005-09-07 |
| RU2005102478A (ru) | 2005-07-20 |
| JP2005538968A (ja) | 2005-12-22 |
| CA2433983A1 (en) | 2003-12-29 |
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