CS272231B2 - Method of phosphinic acid's derivatives production - Google Patents
Method of phosphinic acid's derivatives production Download PDFInfo
- Publication number
- CS272231B2 CS272231B2 CS879002A CS900287A CS272231B2 CS 272231 B2 CS272231 B2 CS 272231B2 CS 879002 A CS879002 A CS 879002A CS 900287 A CS900287 A CS 900287A CS 272231 B2 CS272231 B2 CS 272231B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methyl
- group
- formula
- acid
- carbamoyl
- Prior art date
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- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 title claims description 159
- 238000000034 method Methods 0.000 title claims description 83
- 238000004519 manufacturing process Methods 0.000 title description 2
- -1 8-carboxy-1-naphthaleneacetic acid Chemical compound 0.000 claims description 275
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 227
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 190
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 179
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 163
- 150000001875 compounds Chemical class 0.000 claims description 107
- 229910052739 hydrogen Inorganic materials 0.000 claims description 96
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 65
- 239000007858 starting material Substances 0.000 claims description 57
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 49
- 239000002253 acid Substances 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 40
- 238000002360 preparation method Methods 0.000 claims description 37
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 230000008569 process Effects 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000004122 cyclic group Chemical group 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 229940024606 amino acid Drugs 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 11
- 229960003767 alanine Drugs 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000005544 phthalimido group Chemical group 0.000 claims description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 8
- HVSMSQXVXWYTSI-UHFFFAOYSA-N CCCCCP(O)=O Chemical compound CCCCCP(O)=O HVSMSQXVXWYTSI-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001413 amino acids Chemical group 0.000 claims description 6
- 235000010233 benzoic acid Nutrition 0.000 claims description 6
- 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 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 5
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 150000001559 benzoic acids Chemical class 0.000 claims 1
- 125000004957 naphthylene group Chemical group 0.000 claims 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 162
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 157
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- 239000006260 foam Substances 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- 239000000203 mixture Substances 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 41
- 238000001819 mass spectrum Methods 0.000 description 40
- 125000004494 ethyl ester group Chemical group 0.000 description 38
- 238000001704 evaporation Methods 0.000 description 37
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 36
- 230000008020 evaporation Effects 0.000 description 35
- 239000002904 solvent Substances 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 239000000706 filtrate Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 23
- 229960000583 acetic acid Drugs 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 14
- 150000004702 methyl esters Chemical class 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical class OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 11
- HOCOIDRZLNGZMV-UHFFFAOYSA-N ethoxy(oxido)phosphanium Chemical compound CCO[PH2]=O HOCOIDRZLNGZMV-UHFFFAOYSA-N 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- UIWOZHBYBSGCOS-UHFFFAOYSA-N methoxy(oxido)phosphanium Chemical compound CO[PH2]=O UIWOZHBYBSGCOS-UHFFFAOYSA-N 0.000 description 8
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- ALKYRVXHOSAVTB-UHFFFAOYSA-N 13-amino-azacyclotridecan-2-one Chemical compound NC1CCCCCCCCCCC(=O)N1 ALKYRVXHOSAVTB-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- KBCOVKHULBZKNY-UHFFFAOYSA-N Methyl 4-methylpentanoate Chemical compound COC(=O)CCC(C)C KBCOVKHULBZKNY-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229960003136 leucine Drugs 0.000 description 4
- 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 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- IBRICCXZVPZHRV-UHFFFAOYSA-N (1,3-dioxoisoindol-2-yl)methylphosphinic acid Chemical compound C1=CC=C2C(=O)N(CP(=O)O)C(=O)C2=C1 IBRICCXZVPZHRV-UHFFFAOYSA-N 0.000 description 3
- PIYZBBVETVKTQT-LURJTMIESA-N (2s)-2-(2-methylpropyl)butanedioic acid Chemical compound CC(C)C[C@H](C(O)=O)CC(O)=O PIYZBBVETVKTQT-LURJTMIESA-N 0.000 description 3
- RMYDZBMRAPLPAL-LURJTMIESA-N (3s)-3-(2-methylpropyl)oxolane-2,5-dione Chemical compound CC(C)C[C@H]1CC(=O)OC1=O RMYDZBMRAPLPAL-LURJTMIESA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZBDFLOYLYHAUDS-UHFFFAOYSA-N C1=CC=C2C(=O)N(CP(=O)OC)C(=O)C2=C1 Chemical compound C1=CC=C2C(=O)N(CP(=O)OC)C(=O)C2=C1 ZBDFLOYLYHAUDS-UHFFFAOYSA-N 0.000 description 3
- LRCSKSDZRGTPAF-KIYNQFGBSA-N CNC(=O)[C@H](CC(C)C)NC(=O)C(CC(C)C)CP(O)=O Chemical compound CNC(=O)[C@H](CC(C)C)NC(=O)C(CC(C)C)CP(O)=O LRCSKSDZRGTPAF-KIYNQFGBSA-N 0.000 description 3
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 3
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- ZFYVBXBTMBYWGH-ABLWVSNPSA-N aminomethyl-[4-methyl-2-[[(2S)-4-methyl-1-(methylamino)-1-oxopentan-2-yl]carbamoyl]pentyl]phosphinic acid Chemical compound NCP(O)(=O)CC(CC(C)C)C(N[C@@H](CC(C)C)C(NC)=O)=O ZFYVBXBTMBYWGH-ABLWVSNPSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007859 condensation product Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- CIIJAGYKJKFWLK-ZETCQYMHSA-N (2s)-2-amino-3-methyl-n-propan-2-ylbutanamide Chemical compound CC(C)NC(=O)[C@@H](N)C(C)C CIIJAGYKJKFWLK-ZETCQYMHSA-N 0.000 description 2
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- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
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- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB868629876A GB8629876D0 (en) | 1986-12-15 | 1986-12-15 | Phosphinic acid derivatives |
| GB878722245A GB8722245D0 (en) | 1986-12-15 | 1987-09-22 | Phosphinic acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS900287A2 CS900287A2 (en) | 1990-03-14 |
| CS272231B2 true CS272231B2 (en) | 1991-01-15 |
Family
ID=26291694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS879002A CS272231B2 (en) | 1986-12-15 | 1987-12-09 | Method of phosphinic acid's derivatives production |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US4885283A (fi) |
| EP (1) | EP0276436B1 (fi) |
| CN (1) | CN1017337B (fi) |
| AU (1) | AU606901B2 (fi) |
| CA (1) | CA1326737C (fi) |
| CS (1) | CS272231B2 (fi) |
| DE (1) | DE3786250T2 (fi) |
| DK (1) | DK641687A (fi) |
| ES (1) | ES2056810T3 (fi) |
| FI (1) | FI89059C (fi) |
| HU (1) | HU203109B (fi) |
| IE (1) | IE62334B1 (fi) |
| IL (1) | IL84766A (fi) |
| MC (1) | MC1881A1 (fi) |
| NO (1) | NO171788C (fi) |
| NZ (1) | NZ222824A (fi) |
| PH (1) | PH25030A (fi) |
| PT (1) | PT86366B (fi) |
| ZW (1) | ZW23187A1 (fi) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0347840B1 (en) * | 1988-06-23 | 1995-12-27 | Banyu Pharmaceutical Co., Ltd. | Phosphinic acid derivates |
| US5268384A (en) * | 1990-11-21 | 1993-12-07 | Galardy Richard E | Inhibition of angiogenesis by synthetic matrix metalloprotease inhibitors |
| US5239078A (en) | 1990-11-21 | 1993-08-24 | Glycomed Incorporated | Matrix metalloprotease inhibitors |
| US5114953A (en) * | 1990-11-21 | 1992-05-19 | University Of Florida | Treatment for tissue ulceration |
| US5183900A (en) * | 1990-11-21 | 1993-02-02 | Galardy Richard E | Matrix metalloprotease inhibitors |
| US5189178A (en) * | 1990-11-21 | 1993-02-23 | Galardy Richard E | Matrix metalloprotease inhibitors |
| CA2058797A1 (en) * | 1991-02-01 | 1992-08-02 | Michael John Broadhurst | Amino acid derivatives |
| FR2676059B1 (fr) * | 1991-05-02 | 1993-07-23 | Commissariat Energie Atomique | Nouveaux derives de peptides utilisables comme inhibiteurs de collagenases bacteriennes. |
| EP0520573A1 (en) * | 1991-06-27 | 1992-12-30 | Glaxo Inc. | Cyclic imide derivatives |
| CA2126687A1 (en) * | 1992-01-15 | 1993-07-22 | Charles G. Caldwell | Substituted phosphinic acid-containing peptidyl derivatives as antidegenerative agents |
| US5326760A (en) * | 1992-06-29 | 1994-07-05 | Glaxo, Inc. | Aminobutanoic acid compounds having metalloprotease inhibiting properties |
| US6037472A (en) | 1993-11-04 | 2000-03-14 | Syntex (U.S.A.) Inc. | Matrix metalloprotease inhibitors |
| AU5825094A (en) * | 1993-11-19 | 1995-06-06 | Astra Aktiebolag | Novel dipeptide derivatives |
| GB9405076D0 (en) | 1994-03-16 | 1994-04-27 | Inst Of Ophtalmology | A medical use of matrix metalloproteinase inhibitors |
| US5476847A (en) * | 1994-06-29 | 1995-12-19 | Schering Corporation | Derivatives of phosphinic acid useful as endothelin converting enzyme inhibitors |
| US5831004A (en) * | 1994-10-27 | 1998-11-03 | Affymax Technologies N.V. | Inhibitors of metalloproteases, pharmaceutical compositions comprising same and methods of their use |
| US5840698A (en) * | 1994-10-27 | 1998-11-24 | Affymax Technologies N.V. | Inhibitors of collagenase-1 and stormelysin-I metalloproteases, pharmaceutical compositions comprising same and methods of their use |
| US6011021A (en) * | 1996-06-17 | 2000-01-04 | Guilford Pharmaceuticals Inc. | Methods of cancer treatment using naaladase inhibitors |
| FR2730235A1 (fr) * | 1995-02-06 | 1996-08-09 | Commissariat Energie Atomique | Nouveaux derives de peptides utilisables comme inhibiteur de l'endopeptidase a zinc 24-15 |
| DE69626684T2 (de) * | 1995-12-08 | 2004-04-29 | Agouron Pharmaceuticals, Inc., La Jolla | Metallproteinasehemmer, diesen enthaltende pharmazeutische zusammensetzung und dessen pharmazeutische verwendung und verfahren zu ihrer herstellung |
| US6500948B1 (en) | 1995-12-08 | 2002-12-31 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors-compositions, uses preparation and intermediates thereof |
| DE69624081T2 (de) * | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| US5795877A (en) * | 1996-12-31 | 1998-08-18 | Guilford Pharmaceuticals Inc. | Inhibitors of NAALADase enzyme activity |
| US5672592A (en) * | 1996-06-17 | 1997-09-30 | Guilford Pharmaceuticals Inc. | Certain phosphonomethyl-pentanedioic acid derivatives thereof |
| US6071965A (en) * | 1996-06-17 | 2000-06-06 | Guilford Pharmaceuticals Inc. | Phosphinic alkanoic acid derivatives |
| US6384022B1 (en) | 1996-06-17 | 2002-05-07 | Guilford Pharmaceuticals Inc. | Prodrugs of NAALAdase inhibitors |
| US5902817A (en) * | 1997-04-09 | 1999-05-11 | Guilford Pharmaceuticals Inc. | Certain sulfoxide and sulfone derivatives |
| US6025344A (en) | 1996-06-17 | 2000-02-15 | Guilford Pharmaceuticals Inc. | Certain dioic acid derivatives useful as NAALADase inhibitors |
| US6054444A (en) | 1997-04-24 | 2000-04-25 | Guilford Pharmaceuticals Inc. | Phosphonic acid derivatives |
| US6025345A (en) * | 1996-06-17 | 2000-02-15 | Guilford Pharmaceuticals Inc. | Inhibitors of NAALADase enzyme activity |
| US6046180A (en) * | 1996-06-17 | 2000-04-04 | Guilford Pharmaceuticals Inc. | NAALADase inhibitors |
| US5977090A (en) * | 1996-09-27 | 1999-11-02 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating compulsive disorders using NAALADase inhibitors |
| US5863536A (en) * | 1996-12-31 | 1999-01-26 | Guilford Pharmaceuticals Inc. | Phosphoramidate derivatives |
| NZ333235A (en) | 1996-06-17 | 2000-06-23 | Guilford Pharm Inc | Methods of cancer treatment using naaladase inhibitors |
| HUP9903014A3 (en) * | 1996-07-18 | 2000-08-28 | Pfizer | Phosphinate derivatives having matrix metalloprotease inhibitor effect and medicaments containing the same |
| US6953788B1 (en) | 1996-09-19 | 2005-10-11 | Aventis Pharmaceuticals Inc. | 3-mercaptoacetylamino-1,5-substituted-2-oxo-azepan derivatives useful as inhibitors of matrix metalloproteinase |
| US5962521A (en) * | 1997-04-04 | 1999-10-05 | Guilford Pharmaceuticals Inc. | Hydroxamic acid derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4226610A (en) * | 1978-04-15 | 1980-10-07 | Meiji Selka Kaisha, Ltd. | Herbicidal compounds, preparation thereof and herbicides containing the same |
| JPS60163899A (ja) * | 1984-02-03 | 1985-08-26 | Sankyo Co Ltd | レニン阻害ペプチド類 |
| US4661473A (en) * | 1984-03-27 | 1987-04-28 | Merck & Co., Inc. | Renin inhibitors containing peptide isosteres |
| EP0210545A3 (en) * | 1985-07-24 | 1988-07-20 | Merck & Co. Inc. | Phosphorous containing enzyme inhibitors |
| EP0209848A3 (en) * | 1985-07-24 | 1988-07-27 | Merck & Co. Inc. | Enzyme inhibitors |
-
1987
- 1987-11-30 ZW ZW231/87A patent/ZW23187A1/xx unknown
- 1987-12-01 US US07/126,643 patent/US4885283A/en not_active Expired - Fee Related
- 1987-12-03 AU AU82176/87A patent/AU606901B2/en not_active Ceased
- 1987-12-07 NZ NZ222824A patent/NZ222824A/xx unknown
- 1987-12-07 DK DK641687A patent/DK641687A/da not_active Application Discontinuation
- 1987-12-07 CA CA000553634A patent/CA1326737C/en not_active Expired - Fee Related
- 1987-12-09 CS CS879002A patent/CS272231B2/cs unknown
- 1987-12-09 IL IL8476687A patent/IL84766A/en not_active IP Right Cessation
- 1987-12-10 MC MC871933A patent/MC1881A1/fr unknown
- 1987-12-10 EP EP87118328A patent/EP0276436B1/en not_active Expired - Lifetime
- 1987-12-10 ES ES87118328T patent/ES2056810T3/es not_active Expired - Lifetime
- 1987-12-10 DE DE87118328T patent/DE3786250T2/de not_active Expired - Fee Related
- 1987-12-11 HU HU875593A patent/HU203109B/hu not_active IP Right Cessation
- 1987-12-14 IE IE338387A patent/IE62334B1/en not_active IP Right Cessation
- 1987-12-14 NO NO875214A patent/NO171788C/no unknown
- 1987-12-14 FI FI875484A patent/FI89059C/fi not_active IP Right Cessation
- 1987-12-14 CN CN87101164.6A patent/CN1017337B/zh not_active Expired
- 1987-12-14 PH PH36216A patent/PH25030A/en unknown
- 1987-12-15 PT PT86366A patent/PT86366B/pt not_active IP Right Cessation
-
1989
- 1989-09-22 US US07/410,779 patent/US5006651A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IE873383L (en) | 1988-06-15 |
| FI875484A7 (fi) | 1988-06-16 |
| ZW23187A1 (en) | 1988-06-29 |
| PH25030A (en) | 1991-01-28 |
| NO171788C (no) | 1993-05-05 |
| NO875214L (no) | 1988-06-16 |
| CA1326737C (en) | 1994-02-01 |
| CN87101164A (zh) | 1988-06-29 |
| AU8217687A (en) | 1988-06-16 |
| EP0276436A1 (en) | 1988-08-03 |
| EP0276436B1 (en) | 1993-06-16 |
| AU606901B2 (en) | 1991-02-21 |
| NO875214D0 (no) | 1987-12-14 |
| DK641687A (da) | 1988-06-16 |
| CS900287A2 (en) | 1990-03-14 |
| IL84766A (en) | 1994-02-27 |
| HUT46699A (en) | 1988-11-28 |
| CN1017337B (zh) | 1992-07-08 |
| PT86366A (en) | 1988-01-01 |
| IE62334B1 (en) | 1995-01-25 |
| ES2056810T3 (es) | 1994-10-16 |
| US5006651A (en) | 1991-04-09 |
| US4885283A (en) | 1989-12-05 |
| IL84766A0 (en) | 1988-05-31 |
| MC1881A1 (fr) | 1989-01-24 |
| NZ222824A (en) | 1990-08-28 |
| DE3786250D1 (en) | 1993-07-22 |
| NO171788B (no) | 1993-01-25 |
| DK641687D0 (da) | 1987-12-07 |
| FI89059B (fi) | 1993-04-30 |
| HU203109B (en) | 1991-05-28 |
| FI875484A0 (fi) | 1987-12-14 |
| PT86366B (pt) | 1990-11-20 |
| FI89059C (fi) | 1993-08-10 |
| DE3786250T2 (de) | 1993-10-07 |
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