JP5112583B2 - カソデックス、その誘導体およびその中間体の鏡像体を非対照的に合成する方法 - Google Patents
カソデックス、その誘導体およびその中間体の鏡像体を非対照的に合成する方法 Download PDFInfo
- Publication number
- JP5112583B2 JP5112583B2 JP2001531790A JP2001531790A JP5112583B2 JP 5112583 B2 JP5112583 B2 JP 5112583B2 JP 2001531790 A JP2001531790 A JP 2001531790A JP 2001531790 A JP2001531790 A JP 2001531790A JP 5112583 B2 JP5112583 B2 JP 5112583B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- alkyl
- carbon atoms
- less carbon
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims description 80
- 229940097647 casodex Drugs 0.000 title claims description 33
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 title description 35
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 title description 12
- 239000000543 intermediate Substances 0.000 title description 9
- 230000002194 synthesizing effect Effects 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 156
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 229960000997 bicalutamide Drugs 0.000 claims description 46
- -1 nitro, carboxy, carbamoyl Chemical group 0.000 claims description 46
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- XFTRTWQBIOMVPK-YFKPBYRVSA-N Citramalic acid Natural products OC(=O)[C@](O)(C)CC(O)=O XFTRTWQBIOMVPK-YFKPBYRVSA-N 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- XFTRTWQBIOMVPK-UHFFFAOYSA-N citramalic acid Chemical compound OC(=O)C(O)(C)CC(O)=O XFTRTWQBIOMVPK-UHFFFAOYSA-N 0.000 claims description 26
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 22
- 239000007858 starting material Substances 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 17
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 239000011593 sulfur Substances 0.000 claims description 17
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 17
- 238000011914 asymmetric synthesis Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000001589 carboacyl group Chemical group 0.000 claims description 15
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 230000003647 oxidation Effects 0.000 claims description 12
- 238000007254 oxidation reaction Methods 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
- 238000006114 decarboxylation reaction Methods 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 10
- 125000005277 alkyl imino group Chemical group 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000002346 iodo group Chemical group I* 0.000 claims description 7
- 238000006467 substitution reaction Methods 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
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 239000011260 aqueous acid Substances 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- PMDYLCUKSLBUHO-UHFFFAOYSA-N 4-amino-2-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C#N)C(C(F)(F)F)=C1 PMDYLCUKSLBUHO-UHFFFAOYSA-N 0.000 claims description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 230000031709 bromination Effects 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- YBBJKCMMCRQZMA-UHFFFAOYSA-N pyrithione Chemical compound ON1C=CC=CC1=S YBBJKCMMCRQZMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims 11
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims 6
- 125000002947 alkylene group Chemical group 0.000 claims 5
- 238000006482 condensation reaction Methods 0.000 claims 3
- HVJLGJXEWCPPDB-DOFZRALJSA-N (5z,8z,11z,14z)-3-hydroxyicosa-5,8,11,14-tetraenoic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CC(O)CC(O)=O HVJLGJXEWCPPDB-DOFZRALJSA-N 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims 2
- 230000000911 decarboxylating effect Effects 0.000 claims 2
- 150000003931 anilides Chemical class 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 9
- 229930182820 D-proline Natural products 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000009435 amidation Effects 0.000 description 6
- 238000007112 amidation reaction Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 5
- 150000002596 lactones Chemical class 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000003956 nonsteroidal anti androgen Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000010287 polarization Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 0 ***N*C(*)(*)O Chemical compound ***N*C(*)(*)O 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 238000005882 aldol condensation reaction Methods 0.000 description 2
- 230000002280 anti-androgenic effect Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- LKJPYSCBVHEWIU-QGZVFWFLSA-N (S)-bicalutamide Chemical compound C([C@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-QGZVFWFLSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- VGLCALNOUHFYAD-UHFFFAOYSA-N 3,3-dimethyloxiran-2-ol Chemical compound CC1(C)OC1O VGLCALNOUHFYAD-UHFFFAOYSA-N 0.000 description 1
- CTYJERNWLVBMTF-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-2-hydroxy-2-methylpropanoic acid Chemical compound OC(=O)C(O)(C)CSC1=CC=C(F)C=C1 CTYJERNWLVBMTF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- XFTRTWQBIOMVPK-RXMQYKEDSA-N D-citramalic acid Chemical compound OC(=O)[C@@](O)(C)CC(O)=O XFTRTWQBIOMVPK-RXMQYKEDSA-N 0.000 description 1
- 238000007241 Hunsdiecker-Borodin reaction Methods 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229960003473 androstanolone Drugs 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- GCGWWKKSGPETMI-UHFFFAOYSA-N n-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfanyl-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CSC1=CC=C(F)C=C1 GCGWWKKSGPETMI-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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
- C07D317/34—Oxygen atoms
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16041299P | 1999-10-19 | 1999-10-19 | |
| US60/160,412 | 1999-10-19 | ||
| PCT/US2000/041233 WO2001028990A2 (en) | 1999-10-19 | 2000-10-18 | Methods of asymmetrically synthesizing enantiomers of casodex, its derivatives and intermediates thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003512351A JP2003512351A (ja) | 2003-04-02 |
| JP2003512351A5 JP2003512351A5 (enExample) | 2007-11-29 |
| JP5112583B2 true JP5112583B2 (ja) | 2013-01-09 |
Family
ID=22576803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001531790A Expired - Fee Related JP5112583B2 (ja) | 1999-10-19 | 2000-10-18 | カソデックス、その誘導体およびその中間体の鏡像体を非対照的に合成する方法 |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US6583306B1 (enExample) |
| EP (1) | EP1222165A2 (enExample) |
| JP (1) | JP5112583B2 (enExample) |
| KR (1) | KR20020091047A (enExample) |
| CN (1) | CN1409702A (enExample) |
| AU (1) | AU1968601A (enExample) |
| BR (1) | BR0014889A (enExample) |
| CA (1) | CA2387570A1 (enExample) |
| CZ (1) | CZ20021340A3 (enExample) |
| HK (1) | HK1048298A1 (enExample) |
| HU (1) | HUP0203785A2 (enExample) |
| IL (2) | IL149056A0 (enExample) |
| MX (1) | MXPA02003884A (enExample) |
| NO (1) | NO20021831L (enExample) |
| NZ (1) | NZ518392A (enExample) |
| PL (1) | PL354620A1 (enExample) |
| WO (1) | WO2001028990A2 (enExample) |
| ZA (1) | ZA200202947B (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6071957A (en) | 1996-11-27 | 2000-06-06 | The University Of Tennessee Research Corporation | Irreversible non-steroidal antagonist compound and its use in the treatment of prostate cancer |
| US7759520B2 (en) | 1996-11-27 | 2010-07-20 | University Of Tennessee Research Foundation | Synthesis of selective androgen receptor modulators |
| US6995284B2 (en) | 2000-08-24 | 2006-02-07 | The University Of Tennessee Research Foundation | Synthesis of selective androgen receptor modulators |
| US7026500B2 (en) | 2000-08-24 | 2006-04-11 | University Of Tennessee Research Foundation | Halogenated selective androgen receptor modulators and methods of use thereof |
| US8008348B2 (en) | 2001-12-06 | 2011-08-30 | University Of Tennessee Research Foundation | Treating muscle wasting with selective androgen receptor modulators |
| US6838484B2 (en) | 2000-08-24 | 2005-01-04 | University Of Tennessee Research Foundation | Formulations comprising selective androgen receptor modulators |
| US6998500B2 (en) | 2000-08-24 | 2006-02-14 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| US7622503B2 (en) | 2000-08-24 | 2009-11-24 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| US8445534B2 (en) | 2000-08-24 | 2013-05-21 | University Of Tennessee Research Foundation | Treating androgen decline in aging male (ADAM)-associated conditions with SARMs |
| WO2002100339A2 (en) * | 2001-06-13 | 2002-12-19 | Biogal Gyogyszergyar Rt. | Novel process for preparing rac-bicalutamide and its intermediates |
| US8853266B2 (en) | 2001-12-06 | 2014-10-07 | University Of Tennessee Research Foundation | Selective androgen receptor modulators for treating diabetes |
| PT1463497E (pt) | 2001-12-06 | 2011-12-20 | Gtx Inc | Tratamento do desgaste muscular com moduladores selectivos do receptor de androgénios |
| PT1462442E (pt) | 2001-12-13 | 2009-10-09 | Sumitomo Chemical Co | Cristais de bicalutamida e processo para a sua produção |
| JP4677516B2 (ja) | 2002-02-07 | 2011-04-27 | ユニバーシティ オブ テネシー リサーチ ファウンデーション | Sarmを用いた前立腺肥大症治療 |
| US7344700B2 (en) | 2002-02-28 | 2008-03-18 | University Of Tennessee Research Corporation | Radiolabeled selective androgen receptor modulators and their use in prostate cancer imaging and therapy |
| ES2528764T3 (es) | 2002-02-28 | 2015-02-12 | University Of Tennessee Research Foundation | Moduladores selectivos multisustituidos del receptor de andrógeno y métodos de uso de los mismos |
| US7803970B2 (en) | 2002-02-28 | 2010-09-28 | University Of Tennessee Research Foundation | Multi-substitued selective androgen receptor modulators and methods of use thereof |
| US7772433B2 (en) | 2002-02-28 | 2010-08-10 | University Of Tennessee Research Foundation | SARMS and method of use thereof |
| DE10222104A1 (de) * | 2002-05-17 | 2003-12-04 | Helm Ag | Verfahren zur Herstellung von N-(4'-Cyano-3'-trifluormethyl)-3-(4"-fluorphenylsulfonyl)-2-hydroxy-2-methylpropionamid |
| US7022870B2 (en) | 2002-06-17 | 2006-04-04 | University Of Tennessee Research Foundation | N-bridged selective androgen receptor modulators and methods of use thereof |
| US7741371B2 (en) | 2002-06-17 | 2010-06-22 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
| EP1402924B1 (de) * | 2002-09-04 | 2008-12-31 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Verwendung eines Mittel zur Therapie der Herzhypertrophie |
| US20040063782A1 (en) * | 2002-09-27 | 2004-04-01 | Westheim Raymond J.H. | Bicalutamide forms |
| US6818766B2 (en) | 2002-10-02 | 2004-11-16 | Synthon Bv | Process for making bicalutamide and intermediates thereof |
| CN1726034A (zh) | 2002-10-15 | 2006-01-25 | 田纳西大学研究基金会 | 亚甲基桥连的选择性雄激素受体调节剂及其应用方法 |
| US8309603B2 (en) | 2004-06-07 | 2012-11-13 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| JP4322621B2 (ja) | 2003-10-16 | 2009-09-02 | 住友化学株式会社 | 4’−シアノ−3−[(4−フルオロフェニル)スルホニル]−2−ヒドロキシ−2−メチル−3’−トリフルオロメチルプロピオンアニリドの製造方法 |
| EA200501761A1 (ru) | 2003-12-16 | 2006-04-28 | Джи Ти Икс, ИНК. | Пролекарственные формы селективных модуляторов андрогеновых рецепторов и способы их применения |
| US9889110B2 (en) | 2004-06-07 | 2018-02-13 | University Of Tennessee Research Foundation | Selective androgen receptor modulator for treating hormone-related conditions |
| US9884038B2 (en) | 2004-06-07 | 2018-02-06 | University Of Tennessee Research Foundation | Selective androgen receptor modulator and methods of use thereof |
| WO2008013791A2 (en) * | 2006-07-24 | 2008-01-31 | University Of Delaware | Pan-antagonists for the androgen receptor and androgen receptor mutants associated with anti-androgen withdrawal |
| US10010521B2 (en) | 2006-08-24 | 2018-07-03 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| KR101264820B1 (ko) | 2006-08-24 | 2013-05-22 | 유니버시티 오브 테네시 리서치 파운데이션 | 치환된 아실아닐리드 및 그의 사용 방법 |
| US9730908B2 (en) | 2006-08-24 | 2017-08-15 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| US9844528B2 (en) | 2006-08-24 | 2017-12-19 | University Of Tennessee Research Foundation | SARMs and method of use thereof |
| US7968603B2 (en) | 2007-09-11 | 2011-06-28 | University Of Tennessee Research Foundation | Solid forms of selective androgen receptor modulators |
| ITBO20090236A1 (it) * | 2009-04-10 | 2010-10-11 | Consiglio Nazionale Ricerche | Procedimento per la sintesi di composti per il trattamento del tumore alla prostata |
| US8741951B2 (en) | 2009-04-10 | 2014-06-03 | CNR—Consiglio Nazionale Delle Ricerche | Non-steroidal compounds for androgen receptor modulation |
| WO2011008543A2 (en) * | 2009-06-29 | 2011-01-20 | University Of Delaware | Pan-antagonists for the androgen receptor and androgen receptor mutants associated with anti-androgen withdrawal |
| CN103539710A (zh) * | 2012-07-02 | 2014-01-29 | 国药一心制药有限公司 | 一种(r)-比卡鲁胺的合成方法 |
| JP6226978B2 (ja) | 2012-07-13 | 2017-11-08 | ジーティーエックス・インコーポレイテッド | 選択的アンドロゲン受容体モジュレーター(sarm)によりアンドロゲン受容体(ar)陽性乳癌を処置する方法 |
| US9969683B2 (en) | 2012-07-13 | 2018-05-15 | Gtx, Inc. | Method of treating estrogen receptor (ER)-positive breast cancers with selective androgen receptor modulator (SARMS) |
| US10258596B2 (en) | 2012-07-13 | 2019-04-16 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| US10987334B2 (en) | 2012-07-13 | 2021-04-27 | University Of Tennessee Research Foundation | Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs) |
| US10314807B2 (en) | 2012-07-13 | 2019-06-11 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
| US9622992B2 (en) | 2012-07-13 | 2017-04-18 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
| US9744149B2 (en) | 2012-07-13 | 2017-08-29 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0100172B1 (en) | 1982-07-23 | 1987-08-12 | Imperial Chemical Industries Plc | Amide derivatives |
| GB8617652D0 (en) | 1986-07-18 | 1986-08-28 | Ici Plc | Acylanilide derivatives |
| EP0748220A4 (en) * | 1994-01-21 | 1997-09-10 | Sepracor Inc | METHOD AND COMPOSITIONS FOR TREATING ANDROGEN-DEPENDENT DISEASES USING OPTICALLY PURE R - (-) CASODEX |
| WO1998055153A1 (en) | 1997-06-04 | 1998-12-10 | The University Of Tennessee Research Corporation | Non-steroidal radiolabeled agonist/antagonist compounds and their use in prostate cancer imaging |
| US6186674B1 (en) * | 1998-09-15 | 2001-02-13 | Lucent Technologies, Inc. | Optical sub-assembly package mount |
| US6252762B1 (en) * | 1999-04-21 | 2001-06-26 | Telcordia Technologies, Inc. | Rechargeable hybrid battery/supercapacitor system |
| US6331992B1 (en) * | 2000-04-07 | 2001-12-18 | Stratos Lightwave, Inc. | Small format optical subassembly |
| AU2002231027A1 (en) * | 2000-12-13 | 2002-06-24 | Teraconnect, Inc. | A packaging system for two-dimensional optoelectronic arrays |
| US6821032B2 (en) * | 2002-05-28 | 2004-11-23 | Intel Corporation | Methods of sealing electronic, optical and electro-optical packages and related package and substrate designs |
-
2000
- 2000-10-18 IL IL14905600A patent/IL149056A0/xx unknown
- 2000-10-18 WO PCT/US2000/041233 patent/WO2001028990A2/en not_active Ceased
- 2000-10-18 NZ NZ518392A patent/NZ518392A/en unknown
- 2000-10-18 PL PL00354620A patent/PL354620A1/xx not_active Application Discontinuation
- 2000-10-18 CN CN00817022A patent/CN1409702A/zh active Pending
- 2000-10-18 EP EP00982690A patent/EP1222165A2/en not_active Withdrawn
- 2000-10-18 JP JP2001531790A patent/JP5112583B2/ja not_active Expired - Fee Related
- 2000-10-18 HK HK03100367.2A patent/HK1048298A1/zh unknown
- 2000-10-18 KR KR1020027004966A patent/KR20020091047A/ko not_active Withdrawn
- 2000-10-18 BR BR0014889-0A patent/BR0014889A/pt not_active Application Discontinuation
- 2000-10-18 AU AU19686/01A patent/AU1968601A/en not_active Abandoned
- 2000-10-18 CA CA002387570A patent/CA2387570A1/en not_active Abandoned
- 2000-10-18 US US09/691,621 patent/US6583306B1/en not_active Expired - Lifetime
- 2000-10-18 CZ CZ20021340A patent/CZ20021340A3/cs unknown
- 2000-10-18 HU HU0203785A patent/HUP0203785A2/hu unknown
- 2000-10-18 MX MXPA02003884A patent/MXPA02003884A/es active IP Right Grant
-
2002
- 2002-04-09 IL IL149056A patent/IL149056A/en not_active IP Right Cessation
- 2002-04-15 ZA ZA200202947A patent/ZA200202947B/xx unknown
- 2002-04-18 NO NO20021831A patent/NO20021831L/no not_active Application Discontinuation
-
2003
- 2003-05-23 US US10/444,343 patent/US7022869B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NZ518392A (en) | 2004-02-27 |
| BR0014889A (pt) | 2002-12-31 |
| HK1048298A1 (zh) | 2003-03-28 |
| CN1409702A (zh) | 2003-04-09 |
| WO2001028990A3 (en) | 2001-09-07 |
| ZA200202947B (en) | 2003-09-23 |
| EP1222165A2 (en) | 2002-07-17 |
| US7022869B2 (en) | 2006-04-04 |
| CZ20021340A3 (cs) | 2002-08-14 |
| KR20020091047A (ko) | 2002-12-05 |
| AU1968601A (en) | 2001-04-30 |
| WO2001028990A2 (en) | 2001-04-26 |
| IL149056A (en) | 2011-05-31 |
| JP2003512351A (ja) | 2003-04-02 |
| IL149056A0 (en) | 2002-11-10 |
| US6583306B1 (en) | 2003-06-24 |
| NO20021831D0 (no) | 2002-04-18 |
| CA2387570A1 (en) | 2001-04-26 |
| PL354620A1 (en) | 2004-02-09 |
| US20040030130A1 (en) | 2004-02-12 |
| HUP0203785A2 (hu) | 2003-04-28 |
| NO20021831L (no) | 2002-06-19 |
| MXPA02003884A (es) | 2004-09-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5112583B2 (ja) | カソデックス、その誘導体およびその中間体の鏡像体を非対照的に合成する方法 | |
| TWI271397B (en) | Resolution of intermediates in the synthesis of substantially enantiomerically pure bicalutamide | |
| EP1189898B1 (en) | Process for the synthesis of n-(4-cyano-3-trifluoromethylphenyl)-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methylpropionamide | |
| AU577622B2 (en) | Preparation of (threo)-1-aryl-2-acylamido-3-fluro-1-propanols | |
| JP4358518B2 (ja) | ビカルタミドを含むアシルアニリドおよびそれらの誘導体を合成する方法 | |
| KR20030048408A (ko) | N-(치환 페닐)-3-알킬-, 아릴- 및헤테로아릴설포닐-2-히드록시-2-알킬- 및할로알킬프로판아미드 화합물의 제조방법 | |
| JP2005530795A (ja) | ビカルタミドの製造方法 | |
| CN116217426B (zh) | 由(r)-2-磺酰基丁酸烷基酯合成s-氟丁酰草胺的方法 | |
| JP3361334B2 (ja) | トランスー(5r)−2,4,5−トリ置換2−オキサゾリンの製造方法 | |
| CN117069612B (zh) | 一种合成氰基丙烯酸酯的新方法 | |
| JP2007522115A (ja) | 触媒不斉エポキシ化 | |
| KR100612779B1 (ko) | 키랄 글리시딜프탈이미드를 고광학순도로 제조하는 방법 | |
| RU2414464C2 (ru) | Способ получения n-[3-[(2-метоксифенил)сульфанил]-2-метилпропил]-3,4-дигидро-2н-1,5-бензоксатиепин-3-амина | |
| KR100451414B1 (ko) | 인돌 유도체 및 그 제조 방법 | |
| EP1669347A1 (en) | Process for the preparation of 3-¬(4-fluorophenyl) sulfonyl|-2-hydroxy-2-methyl propionic acid | |
| JP2008534575A (ja) | ビカルタミドの調製のための新規プロセス | |
| EP0403250B1 (en) | Phenylglycidamides useful for preparing alpha-hydroxy-beta-sulfido-arylpropionic acid derivatives | |
| JP2004099505A (ja) | ジアステレオマーヒドロキシカルボン酸アミド及びその製造方法並びに光学活性β置換ラクトンの製造方法 | |
| JPWO2004065368A1 (ja) | トランドラプリル合成中間体の製造方法 | |
| Chand et al. | Novel synthesis of bicalutamide drug substance and their impurities using imidazolium type of ionic liquid | |
| JPH0528210B2 (enExample) | ||
| JP2000080057A (ja) | ラセミ型ビアリ―ルジカルボン酸化合物の製法 | |
| JPH0547526B2 (enExample) | ||
| WO2004043905A1 (ja) | 2−アミノ−3−ヒドロキシプロパン酸誘導体の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20060829 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071012 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071012 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110225 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110518 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110525 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110825 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120302 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120601 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120608 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120903 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120928 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121011 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151019 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |