NZ518392A - Methods of asymmetrically synthesizing enantiomers of casodex, its derivatives and intermediates thereof - Google Patents
Methods of asymmetrically synthesizing enantiomers of casodex, its derivatives and intermediates thereofInfo
- Publication number
- NZ518392A NZ518392A NZ518392A NZ51839200A NZ518392A NZ 518392 A NZ518392 A NZ 518392A NZ 518392 A NZ518392 A NZ 518392A NZ 51839200 A NZ51839200 A NZ 51839200A NZ 518392 A NZ518392 A NZ 518392A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- formula
- alkyl
- carbon atoms
- hydrogen
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 183
- 230000002194 synthesizing effect Effects 0.000 title claims description 41
- 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 31
- 229940097647 casodex Drugs 0.000 title description 30
- 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 13
- 239000000543 intermediate Substances 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 329
- 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 abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 188
- -1 nitro, carboxy, carbamoyl Chemical group 0.000 claims description 179
- 125000004432 carbon atom Chemical group C* 0.000 claims description 127
- 229910052739 hydrogen Inorganic materials 0.000 claims description 80
- 239000001257 hydrogen Substances 0.000 claims description 80
- 229910052736 halogen Inorganic materials 0.000 claims description 77
- 150000002367 halogens Chemical class 0.000 claims description 77
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
- XFTRTWQBIOMVPK-YFKPBYRVSA-N Citramalic acid Natural products OC(=O)[C@](O)(C)CC(O)=O XFTRTWQBIOMVPK-YFKPBYRVSA-N 0.000 claims description 62
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical group 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 59
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 57
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 57
- 125000004414 alkyl thio group Chemical group 0.000 claims description 57
- XFTRTWQBIOMVPK-UHFFFAOYSA-N citramalic acid Chemical compound OC(=O)C(O)(C)CC(O)=O XFTRTWQBIOMVPK-UHFFFAOYSA-N 0.000 claims description 56
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 54
- 229910052717 sulfur Chemical group 0.000 claims description 54
- 239000011593 sulfur Chemical group 0.000 claims description 54
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 50
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 49
- 229960000997 bicalutamide Drugs 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 46
- 229910052760 oxygen Inorganic materials 0.000 claims description 46
- 239000001301 oxygen Substances 0.000 claims description 46
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 42
- 125000001589 carboacyl group Chemical group 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 36
- 125000005277 alkyl imino group Chemical group 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 229920006395 saturated elastomer Polymers 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 31
- 239000007858 starting material Substances 0.000 claims description 25
- 230000003301 hydrolyzing effect Effects 0.000 claims description 24
- 230000000911 decarboxylating effect Effects 0.000 claims description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000001246 bromo group Chemical group Br* 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 125000002346 iodo group Chemical group I* 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000005605 benzo group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 13
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- 150000001261 hydroxy acids Chemical class 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 12
- 238000006114 decarboxylation reaction Methods 0.000 claims description 11
- 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 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 150000002596 lactones Chemical class 0.000 claims description 8
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 claims description 7
- YTGSYRVSBPFKMQ-UHFFFAOYSA-N 2,2,2-tribromoacetaldehyde Chemical compound BrC(Br)(Br)C=O YTGSYRVSBPFKMQ-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- XNNQFQFUQLJSQT-UHFFFAOYSA-N bromo(trichloro)methane Chemical compound ClC(Cl)(Cl)Br XNNQFQFUQLJSQT-UHFFFAOYSA-N 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 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 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- YBBJKCMMCRQZMA-UHFFFAOYSA-N pyrithione Chemical compound ON1C=CC=CC1=S YBBJKCMMCRQZMA-UHFFFAOYSA-N 0.000 claims description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 238000005882 aldol condensation reaction Methods 0.000 claims description 4
- 229910014033 C-OH Inorganic materials 0.000 claims description 3
- 229910014570 C—OH Inorganic materials 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- XFTRTWQBIOMVPK-RXMQYKEDSA-N D-citramalic acid Chemical compound OC(=O)[C@@](O)(C)CC(O)=O XFTRTWQBIOMVPK-RXMQYKEDSA-N 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- GAYDGVKMRJRIBA-UHFFFAOYSA-N dioxolan-4-one Chemical compound O=C1COOC1 GAYDGVKMRJRIBA-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims 9
- 230000002378 acidificating effect Effects 0.000 claims 7
- 239000003637 basic solution Substances 0.000 claims 6
- 239000007800 oxidant agent Substances 0.000 claims 5
- LKJPYSCBVHEWIU-QGZVFWFLSA-N (S)-bicalutamide Chemical group 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 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- ROWMQJJMCWDJDT-UHFFFAOYSA-N tribromomethane Chemical group Br[C](Br)Br ROWMQJJMCWDJDT-UHFFFAOYSA-N 0.000 claims 1
- 239000003643 water by type Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 11
- 238000007254 oxidation reaction Methods 0.000 description 11
- 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
- 230000009435 amidation Effects 0.000 description 6
- 238000007112 amidation reaction Methods 0.000 description 6
- 238000011914 asymmetric synthesis Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000003956 nonsteroidal anti androgen Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 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
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- DRYMMXUBDRJPDS-UHFFFAOYSA-N 2-hydroxy-2-methylpropanamide Chemical compound CC(C)(O)C(N)=O DRYMMXUBDRJPDS-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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- 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
- 230000002280 anti-androgenic effect Effects 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 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
- 238000002474 experimental method Methods 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 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
- VMJNBTIVORMBKT-JEDNCBNOSA-N 2-hydroxy-2-methylbutanedioic acid (2S)-2-hydroxy-2-methylbutanedioic acid Chemical compound OC(=O)C(O)(C)CC(O)=O.OC(=O)[C@](O)(C)CC(O)=O VMJNBTIVORMBKT-JEDNCBNOSA-N 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000007241 Hunsdiecker-Borodin reaction Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-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
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 201000011510 cancer Diseases 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
- 229940125758 compound 15 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 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
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000002307 prostate Anatomy 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
- 229910000030 sodium bicarbonate 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
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16041299P | 1999-10-19 | 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 (1)
| Publication Number | Publication Date |
|---|---|
| NZ518392A true NZ518392A (en) | 2004-02-27 |
Family
ID=22576803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ518392A NZ518392A (en) | 1999-10-19 | 2000-10-18 | Methods of asymmetrically synthesizing enantiomers of casodex, its derivatives and intermediates thereof |
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| CN (1) | CN1409702A (enExample) |
| AU (1) | AU1968601A (enExample) |
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| CA (1) | CA2387570A1 (enExample) |
| CZ (1) | CZ20021340A3 (enExample) |
| HK (1) | HK1048298A1 (enExample) |
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| NO (1) | NO20021831L (enExample) |
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| WO (1) | WO2001028990A2 (enExample) |
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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)
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|---|---|---|---|---|
| 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 |
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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
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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
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Also Published As
| Publication number | Publication date |
|---|---|
| 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 |
| JP5112583B2 (ja) | 2013-01-09 |
| HUP0203785A2 (hu) | 2003-04-28 |
| NO20021831L (no) | 2002-06-19 |
| MXPA02003884A (es) | 2004-09-06 |
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