BRPI0712233A2 - método para preparar um composto de fórmula (xiii); método para preparar um composto de fórmula (xiiia); composto de fórmula (xiiia); composto de fórmula (xiii); composto de fórmula (xiv) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (i); composto de fórmula (xiiia); composto de fórmula (xiva) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (ia); e método de preparar um composto de fórmula (i) ou os sais farmaceuticamente aceitáveis do mesmo - Google Patents
método para preparar um composto de fórmula (xiii); método para preparar um composto de fórmula (xiiia); composto de fórmula (xiiia); composto de fórmula (xiii); composto de fórmula (xiv) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (i); composto de fórmula (xiiia); composto de fórmula (xiva) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (ia); e método de preparar um composto de fórmula (i) ou os sais farmaceuticamente aceitáveis do mesmo Download PDFInfo
- Publication number
- BRPI0712233A2 BRPI0712233A2 BRPI0712233-0A BRPI0712233A BRPI0712233A2 BR PI0712233 A2 BRPI0712233 A2 BR PI0712233A2 BR PI0712233 A BRPI0712233 A BR PI0712233A BR PI0712233 A2 BRPI0712233 A2 BR PI0712233A2
- Authority
- BR
- Brazil
- Prior art keywords
- formula
- compound
- alkyl
- aryl
- heteroaryl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 311
- 150000003839 salts Chemical class 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 54
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 116
- 125000003118 aryl group Chemical group 0.000 claims description 80
- -1 magnesium halide Chemical class 0.000 claims description 64
- 125000001072 heteroaryl group Chemical group 0.000 claims description 53
- 239000002253 acid Substances 0.000 claims description 50
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 46
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 25
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 24
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 150000002902 organometallic compounds Chemical class 0.000 claims description 17
- DVROTRJNFMCILR-UHFFFAOYSA-N CC(C)[Zn] Chemical compound CC(C)[Zn] DVROTRJNFMCILR-UHFFFAOYSA-N 0.000 claims description 15
- FRLYMSHUDNORBC-UHFFFAOYSA-N diisopropylzinc Chemical compound [Zn+2].C[CH-]C.C[CH-]C FRLYMSHUDNORBC-UHFFFAOYSA-N 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 238000006434 Ritter amidation reaction Methods 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 229960000583 acetic acid Drugs 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 239000004305 biphenyl Chemical group 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 11
- 150000002306 glutamic acid derivatives Chemical class 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 38
- 239000002585 base Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 238000011260 co-administration Methods 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 102000005741 Metalloproteases Human genes 0.000 description 10
- 108010006035 Metalloproteases Proteins 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000002837 carbocyclic group Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- UBVBNGDADOJVMM-HNNXBMFYSA-N CC(C)(C)OC(=O)[C@H](CCC(=O)NC(C)(C)CC1=CC=C(C=C1)F)N Chemical compound CC(C)(C)OC(=O)[C@H](CCC(=O)NC(C)(C)CC1=CC=C(C=C1)F)N UBVBNGDADOJVMM-HNNXBMFYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 5
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- NVTZVRJGHWXKET-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-methylpropan-1-ol Chemical compound CC(C)C(O)C1=CC=C(F)C=C1 NVTZVRJGHWXKET-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- 238000003776 cleavage reaction Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
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- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- JITFIYFVPMQJOK-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-methylpropan-2-amine Chemical compound CC(C)(N)CC1=CC=C(F)C=C1 JITFIYFVPMQJOK-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 102000029750 ADAMTS Human genes 0.000 description 2
- 108091022879 ADAMTS Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
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- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
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- 208000023715 Ocular surface disease Diseases 0.000 description 2
- 206010049088 Osteopenia Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000000491 Tendinopathy Diseases 0.000 description 2
- 206010043255 Tendonitis Diseases 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 description 2
- WXNVDQWUGUEUMO-UHFFFAOYSA-N [1-(4-fluorophenyl)-2-methylpropan-2-yl]azanium;chloride Chemical compound Cl.CC(C)(N)CC1=CC=C(F)C=C1 WXNVDQWUGUEUMO-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
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- 208000006673 asthma Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
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- 229940125904 compound 1 Drugs 0.000 description 2
- 208000018180 degenerative disc disease Diseases 0.000 description 2
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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- 239000003475 metalloproteinase inhibitor Substances 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 125000002950 monocyclic group Chemical group 0.000 description 2
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
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- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- LZZRHUUMSXNYBI-UHFFFAOYSA-N (2,4-dichlorophenyl)methyl carbamate Chemical compound NC(=O)OCC1=CC=C(Cl)C=C1Cl LZZRHUUMSXNYBI-UHFFFAOYSA-N 0.000 description 1
- XHTUZBFAOYRMHI-UHFFFAOYSA-N (4-bromophenyl)methyl carbamate Chemical compound NC(=O)OCC1=CC=C(Br)C=C1 XHTUZBFAOYRMHI-UHFFFAOYSA-N 0.000 description 1
- HIIOEWGKFCWTJU-UHFFFAOYSA-N (4-chlorophenyl)methyl carbamate Chemical compound NC(=O)OCC1=CC=C(Cl)C=C1 HIIOEWGKFCWTJU-UHFFFAOYSA-N 0.000 description 1
- SDEOSHAQCMPJIJ-UHFFFAOYSA-N (4-methoxyphenyl)methyl carbamate Chemical compound COC1=CC=C(COC(N)=O)C=C1 SDEOSHAQCMPJIJ-UHFFFAOYSA-N 0.000 description 1
- FPBOSUGVPBRYCA-UHFFFAOYSA-N (4-nitrophenyl)methyl carbamate Chemical compound NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 FPBOSUGVPBRYCA-UHFFFAOYSA-N 0.000 description 1
- JWQMTWCFNZSLNR-DEOSSOPVSA-N (4s)-5-[[1-(4-fluorophenyl)-2-methylpropan-2-yl]amino]-5-oxo-4-[(4-phenylbenzoyl)amino]pentanoic acid Chemical compound O=C([C@H](CCC(O)=O)NC(=O)C=1C=CC(=CC=1)C=1C=CC=CC=1)NC(C)(C)CC1=CC=C(F)C=C1 JWQMTWCFNZSLNR-DEOSSOPVSA-N 0.000 description 1
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- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
- C07C233/13—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/05—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/10—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81029206P | 2006-06-02 | 2006-06-02 | |
| US810,292 | 2006-06-02 | ||
| PCT/US2007/012814 WO2007143014A2 (en) | 2006-06-02 | 2007-05-31 | Methods for preparing glutamic acid derivatives and intermediates thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0712233A2 true BRPI0712233A2 (pt) | 2012-01-10 |
Family
ID=38610555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0712233-0A BRPI0712233A2 (pt) | 2006-06-02 | 2007-05-31 | método para preparar um composto de fórmula (xiii); método para preparar um composto de fórmula (xiiia); composto de fórmula (xiiia); composto de fórmula (xiii); composto de fórmula (xiv) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (i); composto de fórmula (xiiia); composto de fórmula (xiva) ou os sais farmaceuticamente aceitáveis do mesmo; composto de fórmula (ia); e método de preparar um composto de fórmula (i) ou os sais farmaceuticamente aceitáveis do mesmo |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US20080119670A1 (enExample) |
| EP (1) | EP2024326A2 (enExample) |
| JP (1) | JP2009539766A (enExample) |
| KR (1) | KR20090016503A (enExample) |
| CN (1) | CN101460449A (enExample) |
| AR (1) | AR061420A1 (enExample) |
| AU (1) | AU2007254960A1 (enExample) |
| BR (1) | BRPI0712233A2 (enExample) |
| CA (1) | CA2653463A1 (enExample) |
| CR (1) | CR10475A (enExample) |
| EC (1) | ECSP088933A (enExample) |
| IL (1) | IL195513A0 (enExample) |
| MX (1) | MX2008015396A (enExample) |
| NO (1) | NO20084839L (enExample) |
| PA (1) | PA8728901A1 (enExample) |
| PE (1) | PE20080312A1 (enExample) |
| RU (1) | RU2008146043A (enExample) |
| TW (1) | TW200808715A (enExample) |
| WO (1) | WO2007143014A2 (enExample) |
| ZA (1) | ZA200810201B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080058436A (ko) * | 2005-10-13 | 2008-06-25 | 와이어쓰 | 글루탐산 유도체의 제조 방법 |
| EP2089012A2 (en) * | 2006-11-09 | 2009-08-19 | Wyeth | Polymorphs of n²-(1,1'- biphenyl- 4-ylcarbonyl)-n¹-[2-(4-fluorophenyl)-1,1-dimethylethyl]-l-alpha -glutamine |
| US20100216886A1 (en) * | 2006-11-09 | 2010-08-26 | Wyeth | Polymorphs of n2-(1,1'-biphenyl-4-ylcarbonyl)-n1-[2-(4-fluorophenyl)-1,1-dimethylethyl]-l-alpha-glutamine |
| JP5499947B2 (ja) * | 2010-06-30 | 2014-05-21 | 日産化学工業株式会社 | ポリ（５−（メタ）アクリロイル−２−アザアダマンタン−ｎ−オキシル）の製造方法 |
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| WO2006051373A1 (en) * | 2004-11-12 | 2006-05-18 | Pfizer Limited | Compounds for the treatment of diseases |
| MY144590A (en) * | 2005-07-11 | 2011-10-14 | Wyeth Corp | Glutamate aggrecanase inhibitors |
| KR20080058436A (ko) * | 2005-10-13 | 2008-06-25 | 와이어쓰 | 글루탐산 유도체의 제조 방법 |
-
2007
- 2007-05-30 AR ARP070102333A patent/AR061420A1/es unknown
- 2007-05-30 PE PE2007000671A patent/PE20080312A1/es not_active Application Discontinuation
- 2007-05-30 TW TW096119313A patent/TW200808715A/zh unknown
- 2007-05-31 CN CNA2007800201259A patent/CN101460449A/zh active Pending
- 2007-05-31 WO PCT/US2007/012814 patent/WO2007143014A2/en not_active Ceased
- 2007-05-31 RU RU2008146043/04A patent/RU2008146043A/ru not_active Application Discontinuation
- 2007-05-31 EP EP07795533A patent/EP2024326A2/en not_active Withdrawn
- 2007-05-31 CA CA002653463A patent/CA2653463A1/en not_active Abandoned
- 2007-05-31 MX MX2008015396A patent/MX2008015396A/es unknown
- 2007-05-31 JP JP2009513267A patent/JP2009539766A/ja not_active Withdrawn
- 2007-05-31 AU AU2007254960A patent/AU2007254960A1/en not_active Abandoned
- 2007-05-31 BR BRPI0712233-0A patent/BRPI0712233A2/pt not_active IP Right Cessation
- 2007-05-31 KR KR1020087032134A patent/KR20090016503A/ko not_active Withdrawn
- 2007-06-01 PA PA20078728901A patent/PA8728901A1/es unknown
- 2007-06-01 US US11/809,426 patent/US20080119670A1/en not_active Abandoned
-
2008
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- 2008-11-25 IL IL195513A patent/IL195513A0/en unknown
- 2008-12-01 CR CR10475A patent/CR10475A/es not_active Application Discontinuation
- 2008-12-01 ZA ZA200810201A patent/ZA200810201B/xx unknown
- 2008-12-02 EC EC2008008933A patent/ECSP088933A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ECSP088933A (es) | 2009-01-30 |
| TW200808715A (en) | 2008-02-16 |
| PE20080312A1 (es) | 2008-05-14 |
| KR20090016503A (ko) | 2009-02-13 |
| US20080119670A1 (en) | 2008-05-22 |
| JP2009539766A (ja) | 2009-11-19 |
| IL195513A0 (en) | 2009-09-01 |
| AR061420A1 (es) | 2008-08-27 |
| CA2653463A1 (en) | 2007-12-13 |
| EP2024326A2 (en) | 2009-02-18 |
| WO2007143014A2 (en) | 2007-12-13 |
| CR10475A (es) | 2009-01-07 |
| WO2007143014A3 (en) | 2008-01-24 |
| CN101460449A (zh) | 2009-06-17 |
| ZA200810201B (en) | 2010-01-27 |
| AU2007254960A1 (en) | 2007-12-13 |
| MX2008015396A (es) | 2008-12-15 |
| PA8728901A1 (es) | 2009-02-09 |
| NO20084839L (no) | 2008-12-18 |
| RU2008146043A (ru) | 2010-07-20 |
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