NZ538134A - Thiophene compounds - Google Patents
Thiophene compoundsInfo
- Publication number
- NZ538134A NZ538134A NZ538134A NZ53813403A NZ538134A NZ 538134 A NZ538134 A NZ 538134A NZ 538134 A NZ538134 A NZ 538134A NZ 53813403 A NZ53813403 A NZ 53813403A NZ 538134 A NZ538134 A NZ 538134A
- Authority
- NZ
- New Zealand
- Prior art keywords
- nr7r8
- benzimidazol
- formula
- group
- thiophene
- Prior art date
Links
- 150000003577 thiophenes Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 483
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 111
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 60
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 58
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 55
- 238000011282 treatment Methods 0.000 claims abstract description 48
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
- 241001465754 Metazoa Species 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 19
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- 208000035269 cancer or benign tumor Diseases 0.000 claims abstract description 17
- 230000001404 mediated effect Effects 0.000 claims abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 15
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 180
- 238000000034 method Methods 0.000 claims description 136
- -1 -N(alkyl)2 Chemical group 0.000 claims description 121
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 94
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 claims description 61
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 51
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 50
- 239000012453 solvate Substances 0.000 claims description 46
- 230000002401 inhibitory effect Effects 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 230000011278 mitosis Effects 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 239000002246 antineoplastic agent Substances 0.000 claims description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 21
- 230000004663 cell proliferation Effects 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 15
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 15
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical class C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 125000004450 alkenylene group Chemical group 0.000 claims description 9
- 229940127089 cytotoxic agent Drugs 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 7
- 206010014733 Endometrial cancer Diseases 0.000 claims description 7
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 5
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 125000004419 alkynylene group Chemical group 0.000 claims description 5
- 150000003857 carboxamides Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 201000003911 head and neck carcinoma Diseases 0.000 claims description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 241000701447 unidentified baculovirus Species 0.000 claims description 3
- UHCHLTQBLNUYRT-UHFFFAOYSA-N 3-[1-(2-chlorophenyl)ethoxy]-5-(5,6-dimethoxybenzimidazol-1-yl)thiophene-2-carboxamide Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(N)=O)=CC=1OC(C)C1=CC=CC=C1Cl UHCHLTQBLNUYRT-UHFFFAOYSA-N 0.000 claims description 2
- WDJVBZGRDHWJGN-UHFFFAOYSA-N 3-[[2-(difluoromethoxy)phenyl]methoxy]-5-(5,6-dimethoxybenzimidazol-1-yl)thiophene-2-carboxamide Chemical compound C1=2C=C(OC)C(OC)=CC=2N=CN1C(SC=1C(N)=O)=CC=1OCC1=CC=CC=C1OC(F)F WDJVBZGRDHWJGN-UHFFFAOYSA-N 0.000 claims description 2
- TVTINSNESRAREL-UHFFFAOYSA-N 5-(6-bromobenzimidazol-1-yl)-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide Chemical compound NC(=O)C=1SC(N2C3=CC(Br)=CC=C3N=C2)=CC=1OCC1=CC=CC=C1C(F)(F)F TVTINSNESRAREL-UHFFFAOYSA-N 0.000 claims description 2
- KRMSSGBQVGFASL-UHFFFAOYSA-N 5-[6-[3-(dimethylamino)propoxy]-5-methoxybenzimidazol-1-yl]-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide Chemical compound C1=2C=C(OCCCN(C)C)C(OC)=CC=2N=CN1C(SC=1C(N)=O)=CC=1OCC1=CC=CC=C1C(F)(F)F KRMSSGBQVGFASL-UHFFFAOYSA-N 0.000 claims description 2
- 102100021277 Beta-secretase 2 Human genes 0.000 claims 3
- 101710150190 Beta-secretase 2 Proteins 0.000 claims 3
- WOPJVEMFXYHZEE-SRVKXCTJSA-N Asp-Phe-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O WOPJVEMFXYHZEE-SRVKXCTJSA-N 0.000 claims 2
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 claims 2
- CQIIXEHDSZUSAG-QWRGUYRKSA-N Gly-His-His Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 CQIIXEHDSZUSAG-QWRGUYRKSA-N 0.000 claims 2
- KAFZDWMZKGQDEE-SRVKXCTJSA-N His-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KAFZDWMZKGQDEE-SRVKXCTJSA-N 0.000 claims 2
- HAQLBBVZAGMESV-IHRRRGAJSA-N Met-Lys-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O HAQLBBVZAGMESV-IHRRRGAJSA-N 0.000 claims 2
- GDUZTEQRAOXYJS-SRVKXCTJSA-N Ser-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GDUZTEQRAOXYJS-SRVKXCTJSA-N 0.000 claims 2
- 108010028295 histidylhistidine Proteins 0.000 claims 2
- 239000000758 substrate Substances 0.000 claims 2
- INZNSBQAVOKNOU-UHFFFAOYSA-N 5-[5-fluoro-6-(2-morpholin-4-ylethoxy)benzimidazol-1-yl]-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide Chemical compound NC(=O)C=1SC(N2C3=CC(OCCN4CCOCC4)=C(F)C=C3N=C2)=CC=1OCC1=CC=CC=C1C(F)(F)F INZNSBQAVOKNOU-UHFFFAOYSA-N 0.000 claims 1
- YEXNALRMYMPINB-UHFFFAOYSA-N 5-[6-(piperidin-4-ylmethoxy)benzimidazol-1-yl]-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide Chemical compound NC(=O)C=1SC(N2C3=CC(OCC4CCNCC4)=CC=C3N=C2)=CC=1OCC1=CC=CC=C1C(F)(F)F YEXNALRMYMPINB-UHFFFAOYSA-N 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 249
- 238000006243 chemical reaction Methods 0.000 description 202
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 198
- 239000007787 solid Substances 0.000 description 170
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 155
- 239000000203 mixture Substances 0.000 description 128
- 238000005160 1H NMR spectroscopy Methods 0.000 description 110
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 103
- 238000005481 NMR spectroscopy Methods 0.000 description 102
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 73
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 69
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
- 229940093499 ethyl acetate Drugs 0.000 description 62
- 125000001475 halogen functional group Chemical group 0.000 description 59
- 239000010410 layer Substances 0.000 description 58
- 239000000243 solution Substances 0.000 description 58
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 53
- 239000012044 organic layer Substances 0.000 description 52
- 239000000543 intermediate Substances 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 239000002904 solvent Substances 0.000 description 47
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- 235000002639 sodium chloride Nutrition 0.000 description 45
- 238000003756 stirring Methods 0.000 description 44
- 229910001868 water Inorganic materials 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000003153 chemical reaction reagent Substances 0.000 description 37
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- 239000003112 inhibitor Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 29
- 239000012267 brine Substances 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 27
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 27
- 239000004305 biphenyl Substances 0.000 description 27
- 235000010290 biphenyl Nutrition 0.000 description 27
- 239000012442 inert solvent Substances 0.000 description 27
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 27
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
- 125000006267 biphenyl group Chemical group 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- 125000006239 protecting group Chemical group 0.000 description 24
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 24
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 22
- 238000005859 coupling reaction Methods 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- 238000007796 conventional method Methods 0.000 description 19
- 230000008878 coupling Effects 0.000 description 19
- 238000010168 coupling process Methods 0.000 description 19
- 238000000746 purification Methods 0.000 description 18
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
- 238000009472 formulation Methods 0.000 description 17
- 239000012038 nucleophile Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 229960000583 acetic acid Drugs 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229910021529 ammonia Inorganic materials 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
- 229940086542 triethylamine Drugs 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 230000022131 cell cycle Effects 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 108091000080 Phosphotransferase Proteins 0.000 description 13
- 229940034982 antineoplastic agent Drugs 0.000 description 13
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 102000020233 phosphotransferase Human genes 0.000 description 13
- 230000035755 proliferation Effects 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000004429 atom Chemical group 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- UPPIGVQUNSWIIL-UHFFFAOYSA-N methyl 2-chloro-3-oxothiophene-2-carboxylate Chemical compound COC(=O)C1(Cl)SC=CC1=O UPPIGVQUNSWIIL-UHFFFAOYSA-N 0.000 description 10
- 108010056274 polo-like kinase 1 Proteins 0.000 description 10
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 9
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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| US40200802P | 2002-08-08 | 2002-08-08 | |
| PCT/US2003/024272 WO2004014899A1 (en) | 2002-08-08 | 2003-08-04 | Thiophene compounds |
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| DE4329177A1 (de) * | 1993-08-30 | 1995-03-02 | Chemotherapeutisches Forschungsinstitut Georg Speyer Haus | Klonierung eines neuen Mitgliedes der Familie der Serin-Threonin-Kinasen |
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| US20040002524A1 (en) * | 2002-06-24 | 2004-01-01 | Richard Chesworth | Benzimidazole compounds and their use as estrogen agonists/antagonists |
-
2003
- 2003-08-04 BR BR0313160-2A patent/BR0313160A/pt not_active IP Right Cessation
- 2003-08-04 WO PCT/US2003/024272 patent/WO2004014899A1/en not_active Ceased
- 2003-08-04 CA CA002493908A patent/CA2493908A1/en not_active Abandoned
- 2003-08-04 RU RU2005102390/04A patent/RU2296758C2/ru not_active IP Right Cessation
- 2003-08-04 CN CNA038237555A patent/CN1688576A/zh active Pending
- 2003-08-04 KR KR1020057002244A patent/KR20050071471A/ko not_active Ceased
- 2003-08-04 JP JP2004527723A patent/JP2006505522A/ja active Pending
- 2003-08-04 MX MXPA05001544A patent/MXPA05001544A/es unknown
- 2003-08-04 NZ NZ538134A patent/NZ538134A/en unknown
- 2003-08-04 US US10/522,958 patent/US20060074119A1/en not_active Abandoned
- 2003-08-04 PL PL03375532A patent/PL375532A1/xx not_active Application Discontinuation
- 2003-08-04 EP EP03784888A patent/EP1546137A1/en not_active Ceased
- 2003-08-04 AU AU2003265348A patent/AU2003265348B2/en not_active Ceased
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2005
- 2005-01-17 IL IL16632805A patent/IL166328A0/xx unknown
- 2005-01-20 IS IS7657A patent/IS7657A/is unknown
- 2005-01-28 ZA ZA200500864A patent/ZA200500864B/en unknown
- 2005-01-31 NO NO20050525A patent/NO20050525L/no not_active Application Discontinuation
- 2005-03-04 MA MA28130A patent/MA27427A1/fr unknown
-
2008
- 2008-05-01 US US12/113,224 patent/US20080269298A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200500864B (en) | 2006-04-26 |
| MA27427A1 (fr) | 2005-07-01 |
| RU2005102390A (ru) | 2006-01-10 |
| EP1546137A1 (en) | 2005-06-29 |
| US20060074119A1 (en) | 2006-04-06 |
| AU2003265348A1 (en) | 2004-02-25 |
| AU2003265348B2 (en) | 2007-08-16 |
| MXPA05001544A (es) | 2005-04-19 |
| CN1688576A (zh) | 2005-10-26 |
| KR20050071471A (ko) | 2005-07-07 |
| BR0313160A (pt) | 2005-07-12 |
| US20080269298A1 (en) | 2008-10-30 |
| CA2493908A1 (en) | 2004-02-19 |
| NO20050525L (no) | 2005-05-06 |
| IS7657A (is) | 2005-01-20 |
| PL375532A1 (en) | 2005-11-28 |
| WO2004014899A1 (en) | 2004-02-19 |
| IL166328A0 (en) | 2006-01-15 |
| JP2006505522A (ja) | 2006-02-16 |
| RU2296758C2 (ru) | 2007-04-10 |
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