TW200920366A - 5-membered heterocyclic compound - Google Patents
5-membered heterocyclic compound Download PDFInfo
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- TW200920366A TW200920366A TW097136593A TW97136593A TW200920366A TW 200920366 A TW200920366 A TW 200920366A TW 097136593 A TW097136593 A TW 097136593A TW 97136593 A TW97136593 A TW 97136593A TW 200920366 A TW200920366 A TW 200920366A
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- atom
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- 150000000565 5-membered heterocyclic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 273
- 125000004429 atom Chemical group 0.000 claims abstract description 156
- 125000001424 substituent group Chemical group 0.000 claims abstract description 103
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 91
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 81
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 80
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 80
- 125000005843 halogen group Chemical group 0.000 claims abstract description 79
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 64
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 58
- 125000003118 aryl group Chemical group 0.000 claims abstract description 56
- 125000003277 amino group Chemical group 0.000 claims abstract description 51
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 51
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 40
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 37
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 36
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 30
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 16
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 11
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 10
- 230000009858 acid secretion Effects 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 2-fluoropyridylsulfonyl Chemical group 0.000 claims description 469
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 79
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 74
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 64
- 150000001721 carbon Chemical group 0.000 claims description 47
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 28
- 208000011580 syndromic disease Diseases 0.000 claims description 21
- 239000007789 gas Substances 0.000 claims description 20
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 19
- 150000001412 amines Chemical class 0.000 claims description 18
- 239000003112 inhibitor Substances 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
- 208000025865 Ulcer Diseases 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 16
- 231100000397 ulcer Toxicity 0.000 claims description 15
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 10
- 125000005577 anthracene group Chemical group 0.000 claims description 10
- 206010017758 gastric cancer Diseases 0.000 claims description 10
- 208000000689 peptic esophagitis Diseases 0.000 claims description 10
- 201000011549 stomach cancer Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 208000007882 Gastritis Diseases 0.000 claims description 8
- 206010025323 Lymphomas Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 201000011587 gastric lymphoma Diseases 0.000 claims description 8
- 230000002980 postoperative effect Effects 0.000 claims description 8
- 208000023514 Barrett esophagus Diseases 0.000 claims description 7
- 208000023665 Barrett oesophagus Diseases 0.000 claims description 7
- 206010017866 Gastritis haemorrhagic Diseases 0.000 claims description 7
- 208000004210 Pressure Ulcer Diseases 0.000 claims description 7
- 230000000472 traumatic effect Effects 0.000 claims description 7
- 206010011985 Decubitus ulcer Diseases 0.000 claims description 6
- 206010020601 Hyperchlorhydria Diseases 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 201000006549 dyspepsia Diseases 0.000 claims description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 5
- 235000013336 milk Nutrition 0.000 claims description 5
- 239000008267 milk Chemical group 0.000 claims description 5
- 210000004080 milk Anatomy 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 210000002784 stomach Anatomy 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 230000036269 ulceration Effects 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 208000032843 Hemorrhage Diseases 0.000 claims description 2
- 230000000740 bleeding effect Effects 0.000 claims description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 2
- 239000008177 pharmaceutical agent Substances 0.000 claims 2
- 230000001568 sexual effect Effects 0.000 claims 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 229940045799 anthracyclines and related substance Drugs 0.000 claims 1
- 230000004888 barrier function Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- CTYRPMDGLDAWRQ-UHFFFAOYSA-N phenyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1=CC=CC=C1 CTYRPMDGLDAWRQ-UHFFFAOYSA-N 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- FTIMWVSQXCWTAW-UHFFFAOYSA-N ruthenium Chemical compound [Ru].[Ru] FTIMWVSQXCWTAW-UHFFFAOYSA-N 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 abstract description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 26
- 125000000168 pyrrolyl group Chemical group 0.000 abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 13
- 125000002252 acyl group Chemical group 0.000 abstract description 3
- 230000000767 anti-ulcer Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 349
- 239000002585 base Substances 0.000 description 157
- 235000019439 ethyl acetate Nutrition 0.000 description 151
- 239000000203 mixture Substances 0.000 description 128
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- 239000011541 reaction mixture Substances 0.000 description 83
- 235000002639 sodium chloride Nutrition 0.000 description 83
- 239000000243 solution Substances 0.000 description 64
- 230000002829 reductive effect Effects 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 239000000284 extract Substances 0.000 description 55
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 54
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 51
- 235000017557 sodium bicarbonate Nutrition 0.000 description 49
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 49
- 229910052801 chlorine Inorganic materials 0.000 description 46
- 229910052731 fluorine Inorganic materials 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 41
- 125000001309 chloro group Chemical group Cl* 0.000 description 41
- 125000001153 fluoro group Chemical group F* 0.000 description 40
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 38
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 34
- 125000003545 alkoxy group Chemical group 0.000 description 34
- 239000007864 aqueous solution Substances 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 31
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 30
- 125000001544 thienyl group Chemical group 0.000 description 30
- 125000004076 pyridyl group Chemical group 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 28
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 28
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- 229910052740 iodine Inorganic materials 0.000 description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 125000002883 imidazolyl group Chemical group 0.000 description 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 26
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 26
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 25
- 125000001183 hydrocarbyl group Chemical group 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 24
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 235000019441 ethanol Nutrition 0.000 description 22
- 125000002541 furyl group Chemical group 0.000 description 22
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 22
- 239000012046 mixed solvent Substances 0.000 description 20
- CUKCCWBFUGCFBJ-UHFFFAOYSA-N 5-(benzenesulfonyl)-4-bromothiophene-2-carbaldehyde Chemical compound C1=C(C=O)SC(S(=O)(=O)C=2C=CC=CC=2)=C1Br CUKCCWBFUGCFBJ-UHFFFAOYSA-N 0.000 description 19
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 19
- 229960005286 carbaryl Drugs 0.000 description 19
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 229920002678 cellulose Polymers 0.000 description 18
- 239000001913 cellulose Substances 0.000 description 18
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 17
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 17
- 150000002923 oximes Chemical class 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 description 16
- 239000002689 soil Substances 0.000 description 16
- 125000000335 thiazolyl group Chemical group 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 13
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 13
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- 125000003226 pyrazolyl group Chemical group 0.000 description 13
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 12
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 12
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 12
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 229910052751 metal Inorganic materials 0.000 description 12
- 239000002184 metal Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 10
- 150000003973 alkyl amines Chemical class 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 10
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 10
- 229930195733 hydrocarbon Natural products 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 125000003386 piperidinyl group Chemical group 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 9
- 125000003282 alkyl amino group Chemical group 0.000 description 9
- 150000004982 aromatic amines Chemical class 0.000 description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 9
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- ATBKVKDEMSGMTQ-UHFFFAOYSA-N hydrazine triphenylphosphane Chemical compound NN.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 ATBKVKDEMSGMTQ-UHFFFAOYSA-N 0.000 description 9
- 150000002430 hydrocarbons Chemical group 0.000 description 9
- 229910017053 inorganic salt Inorganic materials 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 125000002971 oxazolyl group Chemical group 0.000 description 9
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 9
- 229910052707 ruthenium Inorganic materials 0.000 description 9
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 9
- 241000219112 Cucumis Species 0.000 description 8
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 8
- 239000007983 Tris buffer Substances 0.000 description 8
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 125000006612 decyloxy group Chemical group 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 210000003296 saliva Anatomy 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
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- 235000019354 vermiculite Nutrition 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 150000003772 α-tocopherols Chemical class 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/24—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/64—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007256274 | 2007-09-28 | ||
| JP2008218076 | 2008-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200920366A true TW200920366A (en) | 2009-05-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| TW097136593A TW200920366A (en) | 2007-09-28 | 2008-09-24 | 5-membered heterocyclic compound |
Country Status (9)
| Country | Link |
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| US (1) | US20090156642A1 (enExample) |
| EP (1) | EP2190822B1 (enExample) |
| JP (1) | JP5345140B2 (enExample) |
| KR (1) | KR101558011B1 (enExample) |
| AR (1) | AR068538A1 (enExample) |
| CL (1) | CL2008002834A1 (enExample) |
| PE (1) | PE20090709A1 (enExample) |
| TW (1) | TW200920366A (enExample) |
| WO (1) | WO2009041705A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2009041447A1 (ja) * | 2007-09-28 | 2009-04-02 | Takeda Pharmaceutical Company Limited | 5員複素環化合物 |
| NZ602592A (en) | 2008-07-28 | 2014-01-31 | Takeda Pharmaceutical | Light irradiation resistant pharmaceutical composition |
| KR101629181B1 (ko) | 2008-08-27 | 2016-06-13 | 다케다 야쿠힌 고교 가부시키가이샤 | 피롤 화합물 |
| EP2412713B1 (en) * | 2009-03-26 | 2016-11-30 | Takeda Pharmaceutical Company Limited | Pyrazole compound |
| MX2012000275A (es) | 2009-07-09 | 2012-02-08 | Raqualia Pharma Inc | Antagonista de bomba de acido para el tratamiento de enfermedades involucradas en la motilidad gastrointestinal anormal. |
| EP2526095A1 (en) | 2010-01-19 | 2012-11-28 | Theravance, Inc. | Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents |
| US10039813B2 (en) | 2012-02-07 | 2018-08-07 | Massachusetts Institute Of Technology | Use of antagonists of ghrelin or ghrelin receptor to prevent or treat stress-sensitive psychiatric illness |
| TWI623327B (zh) | 2012-06-27 | 2018-05-11 | 武田藥品工業股份有限公司 | 液狀製劑 |
| WO2014144878A2 (en) * | 2013-03-15 | 2014-09-18 | The Scripps Research Institute | Novel thiol & amino modifying reagents for protein chemistry and methods of use thereof |
| US9724396B2 (en) | 2013-03-15 | 2017-08-08 | Massachusetts Institute Of Technology | Use of antagonists of growth hormone or growth hormone receptor to prevent or treat stress-sensitive psychiatric illness |
| WO2016138099A1 (en) | 2015-02-24 | 2016-09-01 | Massachusetts Institute Of Technology | Use of ghrelin or functional ghrelin receptor agonists to prevent and treat stress-sensitive psychiatric illness |
| CN108191829B (zh) * | 2016-06-30 | 2020-07-03 | 珠海赛隆药业股份有限公司(长沙)医药研发中心 | 应用富马酸沃诺拉赞中间体ⅳ制备富马酸沃诺拉赞的方法 |
| CN108203430A (zh) * | 2016-12-16 | 2018-06-26 | 天地人和生物科技有限公司 | 一种新型可逆性质子泵抑制剂及其制备方法和用途 |
| CN110582503B (zh) | 2017-04-24 | 2022-05-31 | 拜耳公司 | 作为有害物防治剂的稠合双环杂环化合物衍生物 |
| WO2021104256A1 (zh) * | 2019-11-25 | 2021-06-03 | 杭州华东医药集团新药研究院有限公司 | 一种杂环衍生物、其药物组合物及用途 |
| GB201919213D0 (en) | 2019-12-23 | 2020-02-05 | Ucb Biopharma Sprl | Dihydrocyclopenta-Isoquinoline-Sulfanamide derivatives compounds |
| CN111943932B (zh) * | 2020-08-06 | 2023-07-14 | 四川国康药业有限公司 | 一种可以治疗消化性溃疡的3-吡啶磺酰-1-n-杂吡咯衍生物及其制备方法和用途 |
| CN113620930B (zh) * | 2021-07-12 | 2022-08-16 | 南京烁慧医药科技有限公司 | 一种含磺酰胺结构的化合物及其制备方法和应用、一种药物组合物及应用 |
| WO2024196828A2 (en) * | 2023-03-17 | 2024-09-26 | Xibin Liao | Sigma-1 receptor ligands and use thereof |
| CN120208865A (zh) * | 2025-03-11 | 2025-06-27 | 宿迁海德医药化工有限公司 | 一种2-氯-3-肼基吡啶的合成方法 |
Family Cites Families (10)
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| US3285991A (en) * | 1963-03-26 | 1966-11-15 | Union Carbide Corp | Polyepoxides cured with the reaction product of a dihydroxydiphenylsul-fone, an amine, and an aldehyde |
| DK0786455T3 (da) * | 1994-09-26 | 2004-03-29 | Shionogi & Co | Imidazolderivater |
| WO2004012659A2 (en) * | 2002-08-01 | 2004-02-12 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| ES2351393T3 (es) * | 2003-05-26 | 2011-02-03 | Takeda Pharmaceutical Company Limited | Sulfopirroles. |
| US8048909B2 (en) * | 2004-09-30 | 2011-11-01 | Takeda Pharmaceutical Company Limited | Proton pump inhibitors |
| FR2881744B1 (fr) * | 2005-02-09 | 2007-04-27 | Sanofi Aventis Sa | Derives de n-[(4,5-diphenyl-2-thienyl)methyl]amine, leur preparation et leur application en therapeutique |
| US7977488B2 (en) * | 2005-08-30 | 2011-07-12 | Takeda Pharmaceutical Company Limited | 1-heterocyclylsulfonyl, 2-aminomethyl, 5-(hetero-) aryl substituted 1-H-pyrrole derivatives as acid secretion inhibitors |
| FR2894578B1 (fr) * | 2005-12-12 | 2008-02-01 | Sanofi Aventis Sa | Derives heterocycliques, leur preparation et leur application en therapeutique. |
| US7994205B2 (en) * | 2006-03-31 | 2011-08-09 | Takeda Pharmaceutical Company Limited | Aryl-or heteroaryl-sulfonyl compounds as acid secretion inhibitors |
| WO2009041447A1 (ja) * | 2007-09-28 | 2009-04-02 | Takeda Pharmaceutical Company Limited | 5員複素環化合物 |
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2008
- 2008-09-24 US US12/284,636 patent/US20090156642A1/en not_active Abandoned
- 2008-09-24 CL CL2008002834A patent/CL2008002834A1/es unknown
- 2008-09-24 EP EP08834057.5A patent/EP2190822B1/en active Active
- 2008-09-24 PE PE2008001664A patent/PE20090709A1/es not_active Application Discontinuation
- 2008-09-24 TW TW097136593A patent/TW200920366A/zh unknown
- 2008-09-24 KR KR1020107009249A patent/KR101558011B1/ko active Active
- 2008-09-24 WO PCT/JP2008/067784 patent/WO2009041705A2/en not_active Ceased
- 2008-09-24 JP JP2010512025A patent/JP5345140B2/ja active Active
- 2008-09-24 AR ARP080104134A patent/AR068538A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010540412A (ja) | 2010-12-24 |
| WO2009041705A3 (en) | 2009-06-25 |
| AR068538A1 (es) | 2009-11-18 |
| WO2009041705A9 (en) | 2009-08-13 |
| EP2190822A2 (en) | 2010-06-02 |
| EP2190822B1 (en) | 2014-12-31 |
| WO2009041705A2 (en) | 2009-04-02 |
| KR20100080544A (ko) | 2010-07-08 |
| US20090156642A1 (en) | 2009-06-18 |
| JP5345140B2 (ja) | 2013-11-20 |
| CL2008002834A1 (es) | 2009-09-11 |
| PE20090709A1 (es) | 2009-07-15 |
| KR101558011B1 (ko) | 2015-10-06 |
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