AU2003265348B2 - Thiophene compounds - Google Patents
Thiophene compounds Download PDFInfo
- Publication number
- AU2003265348B2 AU2003265348B2 AU2003265348A AU2003265348A AU2003265348B2 AU 2003265348 B2 AU2003265348 B2 AU 2003265348B2 AU 2003265348 A AU2003265348 A AU 2003265348A AU 2003265348 A AU2003265348 A AU 2003265348A AU 2003265348 B2 AU2003265348 B2 AU 2003265348B2
- Authority
- AU
- Australia
- Prior art keywords
- formula
- group
- alkyl
- compound
- benzimidazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- 150000003577 thiophenes Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 461
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 239
- 238000000034 method Methods 0.000 claims description 134
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- -1 -N(alkyl)2 Chemical group 0.000 claims description 107
- 125000005843 halogen group Chemical group 0.000 claims description 69
- 125000005842 heteroatom Chemical group 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 206010028980 Neoplasm Diseases 0.000 claims description 55
- 125000003342 alkenyl group Chemical group 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000000304 alkynyl group Chemical group 0.000 claims description 47
- 239000012453 solvate Substances 0.000 claims description 43
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 claims description 28
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 241001465754 Metazoa Species 0.000 claims description 25
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 25
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
- 201000011510 cancer Diseases 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 12
- 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
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 11
- 125000004450 alkenylene group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 206010014733 Endometrial cancer Diseases 0.000 claims description 7
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 241000894007 species Species 0.000 claims description 7
- 125000004419 alkynylene group Chemical group 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
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 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
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 5
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 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
- 150000003857 carboxamides Chemical class 0.000 claims description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 102100021850 Nardilysin Human genes 0.000 claims description 3
- 108090000970 Nardilysin Proteins 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
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 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
- 201000001441 melanoma Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 102100021277 Beta-secretase 2 Human genes 0.000 claims 2
- 101710150190 Beta-secretase 2 Proteins 0.000 claims 2
- WFRXSXUDWCVSPI-UHFFFAOYSA-N 3h-benzimidazol-5-amine Chemical compound NC1=CC=C2NC=NC2=C1 WFRXSXUDWCVSPI-UHFFFAOYSA-N 0.000 claims 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims 1
- QKDCLUARMDUUKN-XMMPIXPASA-N 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3r)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide Chemical compound N1=C(O[C@H]2CN(CC2)C(=O)C=C)C(CC)=NC(C(N)=O)=C1NC(C=C1)=CC=C1N(CC1)CCC1N1CCN(C)CC1 QKDCLUARMDUUKN-XMMPIXPASA-N 0.000 claims 1
- 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 1
- 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 1
- STOOMQFEJUVAKR-KKUMJFAQSA-N His-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CNC=N1 STOOMQFEJUVAKR-KKUMJFAQSA-N 0.000 claims 1
- 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 1
- 240000004713 Pisum sativum Species 0.000 claims 1
- 235000010582 Pisum sativum Nutrition 0.000 claims 1
- 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 1
- 108010020688 glycylhistidine Proteins 0.000 claims 1
- 108010028295 histidylhistidine Proteins 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 241000701447 unidentified baculovirus Species 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 218
- 238000006243 chemical reaction Methods 0.000 description 200
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 199
- 239000007787 solid Substances 0.000 description 164
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 238000005481 NMR spectroscopy Methods 0.000 description 150
- 239000000203 mixture Substances 0.000 description 126
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
- 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 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- 239000010410 layer Substances 0.000 description 55
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 53
- 210000004027 cell Anatomy 0.000 description 52
- 239000012044 organic layer Substances 0.000 description 50
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
- 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 47
- 239000002904 solvent Substances 0.000 description 47
- 239000000543 intermediate Substances 0.000 description 46
- 235000002639 sodium chloride Nutrition 0.000 description 46
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 238000011282 treatment Methods 0.000 description 41
- 238000003756 stirring Methods 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- 239000003153 chemical reaction reagent Substances 0.000 description 38
- 239000002253 acid Substances 0.000 description 37
- 239000003112 inhibitor Substances 0.000 description 34
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 28
- 230000002401 inhibitory effect Effects 0.000 description 28
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 27
- 239000012267 brine Substances 0.000 description 27
- 239000012442 inert solvent Substances 0.000 description 27
- 230000002829 reductive effect Effects 0.000 description 27
- 229910002027 silica gel Inorganic materials 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 27
- 230000011278 mitosis Effects 0.000 description 24
- 125000006239 protecting group Chemical group 0.000 description 24
- 239000002246 antineoplastic agent Substances 0.000 description 23
- 238000005859 coupling reaction Methods 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 21
- 229910052740 iodine Inorganic materials 0.000 description 21
- 239000004305 biphenyl Substances 0.000 description 20
- 235000010290 biphenyl Nutrition 0.000 description 20
- 230000008878 coupling Effects 0.000 description 20
- 238000010168 coupling process Methods 0.000 description 20
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 20
- 238000007796 conventional method Methods 0.000 description 19
- 125000006267 biphenyl group Chemical group 0.000 description 18
- 230000004663 cell proliferation Effects 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
- 238000000746 purification Methods 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 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
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 229910021529 ammonia Inorganic materials 0.000 description 16
- 108010056274 polo-like kinase 1 Proteins 0.000 description 16
- 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 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 230000022131 cell cycle Effects 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 229940086542 triethylamine Drugs 0.000 description 14
- 229940034982 antineoplastic agent Drugs 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 12
- 125000001475 halogen functional group Chemical group 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
- 125000004429 atom Chemical group 0.000 description 11
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 108091000080 Phosphotransferase Proteins 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 102000020233 phosphotransferase Human genes 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 229940127089 cytotoxic agent Drugs 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 125000006178 methyl benzyl group Chemical group 0.000 description 9
- 230000002062 proliferating effect Effects 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 239000003039 volatile agent Substances 0.000 description 9
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 102000009465 Growth Factor Receptors Human genes 0.000 description 8
- 108010009202 Growth Factor Receptors Proteins 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
- 229910000024 caesium carbonate Inorganic materials 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 229940088597 hormone Drugs 0.000 description 8
- 239000005556 hormone Substances 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
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Classifications
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- 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
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- 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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
Landscapes
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- Veterinary Medicine (AREA)
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- Diabetes (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40200802P | 2002-08-08 | 2002-08-08 | |
| US60/402,008 | 2002-08-08 | ||
| PCT/US2003/024272 WO2004014899A1 (en) | 2002-08-08 | 2003-08-04 | Thiophene compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2003265348A1 AU2003265348A1 (en) | 2004-02-25 |
| AU2003265348B2 true AU2003265348B2 (en) | 2007-08-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2003265348A Ceased AU2003265348B2 (en) | 2002-08-08 | 2003-08-04 | Thiophene compounds |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20060074119A1 (enExample) |
| EP (1) | EP1546137A1 (enExample) |
| JP (1) | JP2006505522A (enExample) |
| KR (1) | KR20050071471A (enExample) |
| CN (1) | CN1688576A (enExample) |
| AU (1) | AU2003265348B2 (enExample) |
| BR (1) | BR0313160A (enExample) |
| CA (1) | CA2493908A1 (enExample) |
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| IS (1) | IS7657A (enExample) |
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- 2003-08-04 RU RU2005102390/04A patent/RU2296758C2/ru not_active IP Right Cessation
- 2003-08-04 JP JP2004527723A patent/JP2006505522A/ja active Pending
- 2003-08-04 KR KR1020057002244A patent/KR20050071471A/ko not_active Ceased
- 2003-08-04 US US10/522,958 patent/US20060074119A1/en not_active Abandoned
- 2003-08-04 BR BR0313160-2A patent/BR0313160A/pt not_active IP Right Cessation
- 2003-08-04 AU AU2003265348A patent/AU2003265348B2/en not_active Ceased
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- 2003-08-04 WO PCT/US2003/024272 patent/WO2004014899A1/en not_active Ceased
- 2003-08-04 CN CNA038237555A patent/CN1688576A/zh active Pending
- 2003-08-04 EP EP03784888A patent/EP1546137A1/en not_active Ceased
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- 2005-03-04 MA MA28130A patent/MA27427A1/fr unknown
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2008
- 2008-05-01 US US12/113,224 patent/US20080269298A1/en not_active Abandoned
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| MXPA05001544A (es) | 2005-04-19 |
| KR20050071471A (ko) | 2005-07-07 |
| US20080269298A1 (en) | 2008-10-30 |
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| PL375532A1 (en) | 2005-11-28 |
| IS7657A (is) | 2005-01-20 |
| RU2296758C2 (ru) | 2007-04-10 |
| AU2003265348A1 (en) | 2004-02-25 |
| NO20050525L (no) | 2005-05-06 |
| IL166328A0 (en) | 2006-01-15 |
| WO2004014899A1 (en) | 2004-02-19 |
| RU2005102390A (ru) | 2006-01-10 |
| MA27427A1 (fr) | 2005-07-01 |
| NZ538134A (en) | 2006-03-31 |
| US20060074119A1 (en) | 2006-04-06 |
| CA2493908A1 (en) | 2004-02-19 |
| CN1688576A (zh) | 2005-10-26 |
| BR0313160A (pt) | 2005-07-12 |
| EP1546137A1 (en) | 2005-06-29 |
| JP2006505522A (ja) | 2006-02-16 |
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