RU2267495C2 - Новые (аминопропил)метилфосфиновые кислоты - Google Patents
Новые (аминопропил)метилфосфиновые кислоты Download PDFInfo
- Publication number
- RU2267495C2 RU2267495C2 RU2002113916/04A RU2002113916A RU2267495C2 RU 2267495 C2 RU2267495 C2 RU 2267495C2 RU 2002113916/04 A RU2002113916/04 A RU 2002113916/04A RU 2002113916 A RU2002113916 A RU 2002113916A RU 2267495 C2 RU2267495 C2 RU 2267495C2
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- Prior art keywords
- amino
- fluoro
- methyl
- compound
- formula
- Prior art date
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- NHVRIDDXGZPJTJ-UHFFFAOYSA-N skf-97,541 Chemical class CP(O)(=O)CCCN NHVRIDDXGZPJTJ-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 6
- 239000012453 solvate Substances 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- QSEZFOAWAVHOBH-UHFFFAOYSA-N (3-amino-2-fluoropropyl)-methylphosphinic acid Chemical compound CP(O)(=O)CC(F)CN QSEZFOAWAVHOBH-UHFFFAOYSA-N 0.000 claims description 5
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 5
- 210000000111 lower esophageal sphincter Anatomy 0.000 claims description 5
- KPELUVFYFBYKOB-QGZVFWFLSA-N (2r)-3-(dibenzylamino)-2-fluoropropan-1-ol Chemical compound C=1C=CC=CC=1CN(C[C@@H](F)CO)CC1=CC=CC=C1 KPELUVFYFBYKOB-QGZVFWFLSA-N 0.000 claims description 4
- DTXCSCJRPZOOAQ-GSVOUGTGSA-N (2r)-3-amino-2-fluoropropan-1-ol Chemical compound NC[C@@H](F)CO DTXCSCJRPZOOAQ-GSVOUGTGSA-N 0.000 claims description 4
- KPELUVFYFBYKOB-KRWDZBQOSA-N (2s)-3-(dibenzylamino)-2-fluoropropan-1-ol Chemical compound C=1C=CC=CC=1CN(C[C@H](F)CO)CC1=CC=CC=C1 KPELUVFYFBYKOB-KRWDZBQOSA-N 0.000 claims description 4
- DTXCSCJRPZOOAQ-VKHMYHEASA-N (2s)-3-amino-2-fluoropropan-1-ol Chemical compound NC[C@H](F)CO DTXCSCJRPZOOAQ-VKHMYHEASA-N 0.000 claims description 4
- HYTZHDBUDDPKNK-UHFFFAOYSA-N (4-amino-3-fluorobutan-2-yl)-methylphosphinic acid Chemical compound CP(=O)(O)C(C)C(F)CN HYTZHDBUDDPKNK-UHFFFAOYSA-N 0.000 claims description 4
- XDZUTZCCXHGOLU-UHFFFAOYSA-N 3-[ethoxy(methyl)phosphoryl]-2-fluoropropanamide Chemical compound CCOP(C)(=O)CC(F)C(N)=O XDZUTZCCXHGOLU-UHFFFAOYSA-N 0.000 claims description 4
- WVTGPBOMAQLPCP-GSVOUGTGSA-O [(2r)-3-amino-2-fluoropropyl]-hydroxy-oxophosphanium Chemical compound NC[C@@H](F)C[P+](O)=O WVTGPBOMAQLPCP-GSVOUGTGSA-O 0.000 claims description 4
- QSEZFOAWAVHOBH-SCSAIBSYSA-N [(2r)-3-amino-2-fluoropropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@H](F)CN QSEZFOAWAVHOBH-SCSAIBSYSA-N 0.000 claims description 4
- WVTGPBOMAQLPCP-VKHMYHEASA-O [(2s)-3-amino-2-fluoropropyl]-hydroxy-oxophosphanium Chemical compound NC[C@H](F)C[P+](O)=O WVTGPBOMAQLPCP-VKHMYHEASA-O 0.000 claims description 4
- QSEZFOAWAVHOBH-BYPYZUCNSA-N [(2s)-3-amino-2-fluoropropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@@H](F)CN QSEZFOAWAVHOBH-BYPYZUCNSA-N 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- MXXNEFMIRPHICR-ZCFIWIBFSA-N tert-butyl n-[(2r)-2-fluoro-3-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@@H](F)CO MXXNEFMIRPHICR-ZCFIWIBFSA-N 0.000 claims description 4
- GVPFWSBKIVUQJO-LURJTMIESA-N tert-butyl n-[(2r)-2-fluoro-3-iodopropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@@H](F)CI GVPFWSBKIVUQJO-LURJTMIESA-N 0.000 claims description 4
- MXXNEFMIRPHICR-LURJTMIESA-N tert-butyl n-[(2s)-2-fluoro-3-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@H](F)CO MXXNEFMIRPHICR-LURJTMIESA-N 0.000 claims description 4
- AYRXSQGCNIIFNH-UHFFFAOYSA-N 3-[ethoxy(methyl)phosphoryl]-2-fluorobutanamide Chemical compound CCOP(C)(=O)C(C)C(F)C(N)=O AYRXSQGCNIIFNH-UHFFFAOYSA-N 0.000 claims description 3
- 206010067171 Regurgitation Diseases 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- LDRFIYIAWLSBGA-UHFFFAOYSA-N ethyl 3-[ethoxy(methyl)phosphoryl]-2-fluorobutanoate Chemical compound CCOC(=O)C(F)C(C)P(C)(=O)OCC LDRFIYIAWLSBGA-UHFFFAOYSA-N 0.000 claims description 3
- GPVFBPLHTWJJFY-UHFFFAOYSA-N ethyl 3-[ethoxy(methyl)phosphoryl]-2-fluoropropanoate Chemical compound CCOC(=O)C(F)CP(C)(=O)OCC GPVFBPLHTWJJFY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- OBKSTEOVEUUBBH-KRWDZBQOSA-N methyl (2s)-3-(dibenzylamino)-2-fluoropropanoate Chemical compound C=1C=CC=CC=1CN(C[C@H](F)C(=O)OC)CC1=CC=CC=C1 OBKSTEOVEUUBBH-KRWDZBQOSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 230000008673 vomiting Effects 0.000 claims description 3
- 206010011224 Cough Diseases 0.000 claims description 2
- 206010012335 Dependence Diseases 0.000 claims description 2
- 206010015137 Eructation Diseases 0.000 claims description 2
- 208000031361 Hiccup Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 208000027687 belching Diseases 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 201000006549 dyspepsia Diseases 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 230000020341 sensory perception of pain Effects 0.000 claims description 2
- 230000001052 transient effect Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 4
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- YNTOKMNHRPSGFU-UHFFFAOYSA-N n-Propyl carbamate Chemical compound CCCOC(N)=O YNTOKMNHRPSGFU-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 60
- 230000000694 effects Effects 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 6
- FUUPFUIGNBPCAY-UHFFFAOYSA-N (3-amino-2-hydroxypropyl)-methylphosphinic acid Chemical class CP(O)(=O)CC(O)CN FUUPFUIGNBPCAY-UHFFFAOYSA-N 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 abstract description 2
- LRJYUBWOCIHSCA-UHFFFAOYSA-N (3-amino-2-hydroxypropyl)-(difluoromethyl)phosphinic acid Chemical compound NCC(O)CP(O)(=O)C(F)F LRJYUBWOCIHSCA-UHFFFAOYSA-N 0.000 abstract description 2
- CJTIGOOCRLKWAP-UHFFFAOYSA-N (3-amino-2-oxopropyl)-methylphosphinic acid Chemical compound CP(O)(=O)CC(=O)CN CJTIGOOCRLKWAP-UHFFFAOYSA-N 0.000 abstract description 2
- FUUPFUIGNBPCAY-SCSAIBSYSA-N [(2r)-3-amino-2-hydroxypropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@H](O)CN FUUPFUIGNBPCAY-SCSAIBSYSA-N 0.000 abstract description 2
- FUUPFUIGNBPCAY-BYPYZUCNSA-N [(2s)-3-amino-2-hydroxypropyl]-methylphosphinic acid Chemical compound CP(O)(=O)C[C@@H](O)CN FUUPFUIGNBPCAY-BYPYZUCNSA-N 0.000 abstract description 2
- 230000007721 medicinal effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 239000011541 reaction mixture Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 20
- 239000000908 ammonium hydroxide Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- -1 hydroxy, mercapto Chemical class 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 125000005843 halogen group Chemical group 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 10
- 230000003301 hydrolyzing effect Effects 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000003185 4 aminobutyric acid B receptor stimulating agent Substances 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical group OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 229960000794 baclofen Drugs 0.000 description 4
- 239000002585 base Chemical class 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000006884 silylation reaction Methods 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 206010021118 Hypotonia Diseases 0.000 description 3
- 238000007126 N-alkylation reaction Methods 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000036640 muscle relaxation Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- GVPFWSBKIVUQJO-ZCFIWIBFSA-N tert-butyl n-[(2s)-2-fluoro-3-iodopropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@H](F)CI GVPFWSBKIVUQJO-ZCFIWIBFSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000005309 thioalkoxy group Chemical group 0.000 description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- GJYJYFHBOBUTBY-UHFFFAOYSA-N alpha-camphorene Chemical compound CC(C)=CCCC(=C)C1CCC(CCC=C(C)C)=CC1 GJYJYFHBOBUTBY-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 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
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- AGWPTXYSXUNKLV-UHFFFAOYSA-N ethoxy-methyl-oxophosphanium Chemical compound CCO[P+](C)=O AGWPTXYSXUNKLV-UHFFFAOYSA-N 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 229940035363 muscle relaxants Drugs 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003653 radioligand binding assay Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 210000002182 synaptic membrane Anatomy 0.000 description 2
- 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 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XKCQASMZNPBLKI-UHFFFAOYSA-N phosphorosooxymethane Chemical group COP=O XKCQASMZNPBLKI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/08—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9904507-2 | 1999-12-09 | ||
| SE9904507A SE9904507D0 (sv) | 1999-12-09 | 1999-12-09 | New compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2002113916A RU2002113916A (ru) | 2004-01-10 |
| RU2267495C2 true RU2267495C2 (ru) | 2006-01-10 |
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| RU2002113916/04A RU2267495C2 (ru) | 1999-12-09 | 2000-12-04 | Новые (аминопропил)метилфосфиновые кислоты |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6596711B1 (enExample) |
| EP (1) | EP1239843A1 (enExample) |
| JP (1) | JP2003516346A (enExample) |
| KR (1) | KR100752010B1 (enExample) |
| CN (1) | CN1200713C (enExample) |
| AR (1) | AR033350A1 (enExample) |
| AU (1) | AU780259B2 (enExample) |
| BR (1) | BR0016291A (enExample) |
| CA (1) | CA2393510A1 (enExample) |
| CO (1) | CO5261538A1 (enExample) |
| CZ (1) | CZ20021984A3 (enExample) |
| EE (1) | EE200200287A (enExample) |
| HU (1) | HUP0300386A3 (enExample) |
| IL (2) | IL150090A0 (enExample) |
| IS (1) | IS6409A (enExample) |
| MX (1) | MXPA02005537A (enExample) |
| NO (1) | NO20022729L (enExample) |
| NZ (1) | NZ519377A (enExample) |
| PL (1) | PL357115A1 (enExample) |
| RU (1) | RU2267495C2 (enExample) |
| SE (1) | SE9904507D0 (enExample) |
| SK (1) | SK7632002A3 (enExample) |
| TW (1) | TWI225415B (enExample) |
| UA (1) | UA73149C2 (enExample) |
| WO (1) | WO2001041743A1 (enExample) |
| ZA (1) | ZA200204122B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| SE9904508D0 (sv) * | 1999-12-09 | 1999-12-09 | Astra Ab | New compounds |
| US7319095B2 (en) * | 1999-12-09 | 2008-01-15 | Astrazeneca Ab | Use of GABAB receptor agonists |
| TW200407110A (en) * | 2001-11-23 | 2004-05-16 | Astrazeneca Ab | New use for the treatment of gastroesophageal reflux disease |
| SE0201939D0 (sv) * | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New combination |
| SE0201940D0 (sv) * | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New combination II |
| DE10305463A1 (de) * | 2003-02-04 | 2004-08-12 | Schering Ag | Enantiomerenreines (4S,8S)- und (4R,8R)-4-p-Nitrobenzyl-8-methyl-3,6,9-triza-3N,6N,9N-tricarboxymethyl-1,11-undecandisäure und deren Abkömmlinge, Verfahren zu deren Herstellung und Verwendung zur Herstellung pharmazeutischer Mittel |
| SE0401653D0 (sv) | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | New compounds |
| SE0402462D0 (sv) * | 2004-10-08 | 2004-10-08 | Astrazeneca Ab | New process |
| AU2006327315A1 (en) | 2005-12-23 | 2007-06-28 | Astrazeneca Ab | Imidazole derivatives for the treatment of gastrointestinal disorders |
| AU2006327317B2 (en) | 2005-12-23 | 2010-11-25 | Astrazeneca Ab | GABA-B receptor modulators |
| US8026384B2 (en) | 2007-05-04 | 2011-09-27 | Astrazeneca Ab | Process for the synthesis of alkyl phosphinic acids by initiation of an amine and an amineoxide |
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| WO2009082344A1 (en) * | 2007-12-21 | 2009-07-02 | Astrazeneca Ab | Novel process for making (2r)-(3-amino-2-fluoropropyl)phosphinic acid form a |
| EP2235027A4 (en) * | 2007-12-21 | 2011-06-22 | Astrazeneca Ab | NEW CRYSTALLINE FORM OF (2R) - (3-AMINO-2-FLUOROPROPYL) PHOSPHINIC ACID |
| JP2011026260A (ja) * | 2009-07-28 | 2011-02-10 | Central Glass Co Ltd | ３位に脱離基を有する２−フルオロプロピルアミン保護体または該アミンｎ−アルキル保護体 |
| WO2011113904A1 (en) | 2010-03-17 | 2011-09-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Medicaments for the prevention and treatment of a disease associated with retinal ganglion cell degeneration |
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- 2000-04-12 UA UA2002064506A patent/UA73149C2/uk unknown
- 2000-11-27 TW TW089125146A patent/TWI225415B/zh not_active IP Right Cessation
- 2000-12-04 CZ CZ20021984A patent/CZ20021984A3/cs unknown
- 2000-12-04 CA CA002393510A patent/CA2393510A1/en not_active Abandoned
- 2000-12-04 WO PCT/SE2000/002427 patent/WO2001041743A1/en not_active Ceased
- 2000-12-04 MX MXPA02005537A patent/MXPA02005537A/es active IP Right Grant
- 2000-12-04 HU HU0300386A patent/HUP0300386A3/hu unknown
- 2000-12-04 PL PL00357115A patent/PL357115A1/xx not_active IP Right Cessation
- 2000-12-04 EP EP00986117A patent/EP1239843A1/en not_active Withdrawn
- 2000-12-04 NZ NZ519377A patent/NZ519377A/en unknown
- 2000-12-04 EE EEP200200287A patent/EE200200287A/xx unknown
- 2000-12-04 CN CNB008169063A patent/CN1200713C/zh not_active Expired - Fee Related
- 2000-12-04 IL IL15009000A patent/IL150090A0/xx active IP Right Grant
- 2000-12-04 BR BR0016291-4A patent/BR0016291A/pt not_active Application Discontinuation
- 2000-12-04 US US09/786,220 patent/US6596711B1/en not_active Expired - Fee Related
- 2000-12-04 AU AU22412/01A patent/AU780259B2/en not_active Ceased
- 2000-12-04 KR KR1020027007356A patent/KR100752010B1/ko not_active Expired - Fee Related
- 2000-12-04 SK SK763-2002A patent/SK7632002A3/sk not_active Application Discontinuation
- 2000-12-04 RU RU2002113916/04A patent/RU2267495C2/ru not_active Application Discontinuation
- 2000-12-04 JP JP2001543088A patent/JP2003516346A/ja active Pending
- 2000-12-05 AR ARP000106429A patent/AR033350A1/es unknown
- 2000-12-06 CO CO00093168A patent/CO5261538A1/es not_active Application Discontinuation
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2002
- 2002-05-23 ZA ZA200204122A patent/ZA200204122B/xx unknown
- 2002-06-06 IS IS6409A patent/IS6409A/is unknown
- 2002-06-06 IL IL150090A patent/IL150090A/en not_active IP Right Cessation
- 2002-06-07 NO NO20022729A patent/NO20022729L/no not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2001041743A1 (en) | 2001-06-14 |
| CA2393510A1 (en) | 2001-06-14 |
| CN1200713C (zh) | 2005-05-11 |
| CZ20021984A3 (cs) | 2002-11-13 |
| SE9904507D0 (sv) | 1999-12-09 |
| NO20022729L (no) | 2002-07-09 |
| EP1239843A1 (en) | 2002-09-18 |
| IL150090A (en) | 2006-08-01 |
| PL357115A1 (en) | 2004-07-12 |
| HUP0300386A2 (hu) | 2003-07-28 |
| KR20020060993A (ko) | 2002-07-19 |
| IS6409A (is) | 2002-06-06 |
| IL150090A0 (en) | 2002-12-01 |
| RU2002113916A (ru) | 2004-01-10 |
| AU2241201A (en) | 2001-06-18 |
| ZA200204122B (en) | 2003-10-29 |
| EE200200287A (et) | 2003-08-15 |
| HUP0300386A3 (en) | 2005-08-29 |
| TWI225415B (en) | 2004-12-21 |
| BR0016291A (pt) | 2002-08-13 |
| AU780259B2 (en) | 2005-03-10 |
| KR100752010B1 (ko) | 2007-08-28 |
| US6596711B1 (en) | 2003-07-22 |
| UA73149C2 (en) | 2005-06-15 |
| AR033350A1 (es) | 2003-12-17 |
| JP2003516346A (ja) | 2003-05-13 |
| NO20022729D0 (no) | 2002-06-07 |
| SK7632002A3 (en) | 2003-03-04 |
| MXPA02005537A (es) | 2004-09-10 |
| NZ519377A (en) | 2003-11-28 |
| HK1053066A1 (en) | 2003-10-10 |
| CN1413104A (zh) | 2003-04-23 |
| CO5261538A1 (es) | 2003-03-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20050214 |
|
| FZ9A | Application not withdrawn (correction of the notice of withdrawal) |
Effective date: 20050214 |