NO301472B1 - Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav - Google Patents
Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav Download PDFInfo
- Publication number
- NO301472B1 NO301472B1 NO923857A NO923857A NO301472B1 NO 301472 B1 NO301472 B1 NO 301472B1 NO 923857 A NO923857 A NO 923857A NO 923857 A NO923857 A NO 923857A NO 301472 B1 NO301472 B1 NO 301472B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- dimethylamino
- dioxo
- bis
- tetrahydroxy
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 117
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- -1 monosubstituted amino Chemical group 0.000 claims description 187
- 125000000217 alkyl group Chemical group 0.000 claims description 153
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 75
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 55
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 52
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 42
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 42
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 41
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 38
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 27
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000003435 aroyl group Chemical group 0.000 claims description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 12
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 8
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
- 229910052751 metal Chemical class 0.000 claims description 8
- 239000002184 metal Chemical class 0.000 claims description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 8
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 8
- 229910052711 selenium Inorganic materials 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 7
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 239000000039 congener Substances 0.000 claims description 6
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000005252 haloacyl group Chemical group 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 claims description 4
- QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 4
- 125000005916 2-methylpentyl group Chemical group 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 4
- QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 229910052791 calcium Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229960002449 glycine Drugs 0.000 claims description 4
- 235000013905 glycine and its sodium salt Nutrition 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 4
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 claims description 4
- 125000006628 propoxycarbonylamino group Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Chemical group 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 claims description 4
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 4
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 235000001014 amino acid Nutrition 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 3
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000004411 aluminium Substances 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 2
- 125000005228 aryl sulfonate group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 235000018417 cysteine Nutrition 0.000 claims description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011572 manganese Substances 0.000 claims description 2
- 229910052748 manganese Inorganic materials 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004706 n-propylthio group Chemical group C(CC)S* 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- 125000002981 3-(trifluoromethyl)benzoyl group Chemical group FC(C=1C=C(C(=O)*)C=CC1)(F)F 0.000 claims 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims 1
- ZXFCRFYULUUSDW-UHFFFAOYSA-N C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1CC(O)=C(C(=O)N)C2=O Chemical compound C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1CC(O)=C(C(=O)N)C2=O ZXFCRFYULUUSDW-UHFFFAOYSA-N 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims 1
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- RFSXUZYKRDCQTD-UHFFFAOYSA-N S(=O)(=O)(O)O.COC(N)=O Chemical compound S(=O)(=O)(O)O.COC(N)=O RFSXUZYKRDCQTD-UHFFFAOYSA-N 0.000 claims 1
- 125000005110 aryl thio group Chemical group 0.000 claims 1
- 125000006309 butyl amino group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims 1
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 125000006308 propyl amino group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 58
- 239000004098 Tetracycline Substances 0.000 abstract description 40
- 235000019364 tetracycline Nutrition 0.000 abstract description 35
- 150000003522 tetracyclines Chemical class 0.000 abstract description 28
- 229940040944 tetracyclines Drugs 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 11
- 239000000543 intermediate Substances 0.000 abstract description 7
- 238000001228 spectrum Methods 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 147
- 239000000047 product Substances 0.000 description 119
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 48
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 46
- 239000007787 solid Substances 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- 239000000203 mixture Substances 0.000 description 37
- 229960002180 tetracycline Drugs 0.000 description 25
- 229930101283 tetracycline Natural products 0.000 description 25
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyrrole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Furan Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Moulding By Coating Moulds (AREA)
- Saccharide Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77157691A | 1991-10-04 | 1991-10-04 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO923857D0 NO923857D0 (no) | 1992-10-02 |
| NO923857L NO923857L (no) | 1993-04-05 |
| NO301472B1 true NO301472B1 (no) | 1997-11-03 |
Family
ID=25092264
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO923857A NO301472B1 (no) | 1991-10-04 | 1992-10-02 | Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav |
| NO2006015C NO2006015I2 (no) | 1991-10-04 | 2006-11-15 | Tigecyklin. |
| NO2017037C NO2017037I2 (no) | 1991-10-04 | 2017-08-01 | Tygacil er et antibiotika inneholdende en tetracyklinforbindelse betegnet tigecyklin - Forlenget SPC |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2006015C NO2006015I2 (no) | 1991-10-04 | 2006-11-15 | Tigecyklin. |
| NO2017037C NO2017037I2 (no) | 1991-10-04 | 2017-08-01 | Tygacil er et antibiotika inneholdende en tetracyklinforbindelse betegnet tigecyklin - Forlenget SPC |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP0536515B1 (enExample) |
| JP (1) | JP3186863B2 (enExample) |
| KR (1) | KR100269072B1 (enExample) |
| CN (1) | CN1048240C (enExample) |
| AT (1) | ATE211128T1 (enExample) |
| AU (1) | AU654049B2 (enExample) |
| BR (1) | BR1100853A (enExample) |
| CA (1) | CA2079692C (enExample) |
| CL (1) | CL2004001623A1 (enExample) |
| CZ (2) | CZ309397A3 (enExample) |
| DE (4) | DE122006000058I2 (enExample) |
| DK (1) | DK0536515T3 (enExample) |
| ES (1) | ES2168254T3 (enExample) |
| FI (1) | FI114911B (enExample) |
| HU (2) | HU219973B (enExample) |
| IL (3) | IL103320A (enExample) |
| LU (1) | LU91279I2 (enExample) |
| MX (1) | MX9205532A (enExample) |
| NL (1) | NL300244I1 (enExample) |
| NO (3) | NO301472B1 (enExample) |
| NZ (1) | NZ244585A (enExample) |
| PL (4) | PL172282B1 (enExample) |
| PT (1) | PT536515E (enExample) |
| SG (1) | SG52361A1 (enExample) |
| SK (2) | SK284826B6 (enExample) |
| TW (1) | TW275616B (enExample) |
| ZA (1) | ZA927607B (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5284963A (en) * | 1992-08-13 | 1994-02-08 | American Cyanamid Company | Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines |
| US5328902A (en) * | 1992-08-13 | 1994-07-12 | American Cyanamid Co. | 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| US5420272A (en) * | 1992-08-13 | 1995-05-30 | American Cyanamid Company | 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines |
| WO1995022529A1 (en) * | 1994-02-17 | 1995-08-24 | Pfizer Inc. | 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
| US8106225B2 (en) | 1999-09-14 | 2012-01-31 | Trustees Of Tufts College | Methods of preparing substituted tetracyclines with transition metal-based chemistries |
| CZ301835B6 (cs) | 1999-09-14 | 2010-07-07 | Trustees Of Tufts College | Zpusob prípravy 7-, 9- nebo 13- substituované tetracyklinové slouceniny, reaktivní tetracyklinový chemický komplex a tetracyklinová sloucenina substituovaná v poloze 7 nebo 9 |
| ATE365710T1 (de) | 2000-03-31 | 2007-07-15 | Tufts College | 7- und 9-carbamat, harnstoff, thioharnstoff, thiocarbamat und heteroaryl-amino substituierte tetracyclinverbindungen |
| AU2001259701A1 (en) * | 2000-05-15 | 2001-11-26 | Paratek Pharmaceuticals, Inc | 7-substituted fused ring tetracycline compounds |
| US7094806B2 (en) | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
| CZ2003344A3 (cs) * | 2000-07-07 | 2003-05-14 | Trustees Of Tufts College | 9-Substituované minocyklinové sloučeniny |
| AU2002250331A1 (en) | 2001-03-13 | 2002-09-24 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
| WO2002072532A1 (en) | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7, 9-substituted tetracycline compounds |
| US7553828B2 (en) | 2001-03-13 | 2009-06-30 | Paratek Pharmaceuticals, Inc. | 9-aminomethyl substituted minocycline compounds |
| EP1241160A1 (en) | 2001-03-13 | 2002-09-18 | Glaxo Group Limited | Tetracycline derivatives and their use as antibiotic agents |
| EP1399414B1 (en) * | 2001-04-24 | 2010-01-13 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for the treatment of malaria |
| EP1408987B1 (en) | 2001-07-13 | 2013-04-10 | Paratek Pharmaceuticals, Inc. | Tetracycline compounds having target therapeutic activities |
| WO2003055441A2 (en) | 2001-08-02 | 2003-07-10 | Paratek Pharmaceuticals, Inc. | Medicaments |
| EP2311797A1 (en) | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| JP2005526754A (ja) * | 2002-03-08 | 2005-09-08 | パラテック ファーマシューティカルズ インコーポレイテッド | アミノメチル置換されたテトラサイクリン化合物 |
| WO2005009943A2 (en) | 2003-07-09 | 2005-02-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| UA83266C2 (en) * | 2003-12-08 | 2008-06-25 | Уайет | Oxazole derivatives of tetracyclines |
| KR101171408B1 (ko) | 2004-05-21 | 2012-08-08 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 테트라사이클린 및 이의 유사체의 합성 |
| US7534766B2 (en) | 2004-11-05 | 2009-05-19 | Wyeth | Glucuronide metabolites and epimers thereof of tigecycline |
| AR057649A1 (es) | 2005-05-27 | 2007-12-12 | Wyeth Corp | Formas solidas cristalinas de tigeciclina y metodos para preparar las mismas |
| JP2009507793A (ja) * | 2005-08-31 | 2009-02-26 | ワイス | グリシルサイクリンの９−アミノカルボニル置換誘導体 |
| WO2007133797A2 (en) | 2006-05-15 | 2007-11-22 | Paratek Pharmaceuticals, Inc. | Methods of regulating expression of genes or of gene products using substituted tetracycline compounds |
| RU2483072C2 (ru) | 2007-11-29 | 2013-05-27 | Актелион Фармасьютиклз Лтд | Производные фосфоновой кислоты и их применение в качестве антагонистов рецептора p2y12 |
| PT2271348T (pt) | 2008-03-28 | 2018-04-16 | Paratek Pharm Innc | Formulação de comprimido oral de composto de tetraciclina |
| ITMI20080807A1 (it) | 2008-05-05 | 2009-11-06 | Antibioticos Spa | Procedimento per la preparazione di tigeciclina in forma amorfa |
| TWI585071B (zh) | 2008-05-19 | 2017-06-01 | 派洛泰克藥物股份有限公司 | 四環素化合物之甲苯磺酸鹽及同素異形體 |
| HUE026562T2 (hu) * | 2008-08-08 | 2016-06-28 | Tetraphase Pharmaceuticals Inc | C7-fluor-helyettesített tetraciklin vegyületek |
| WO2010126607A2 (en) | 2009-04-30 | 2010-11-04 | President And Fellows Of Harvard College | Synthesis of tetracyclines and intermediates thereto |
| CN102459153A (zh) | 2009-05-08 | 2012-05-16 | 四相制药公司 | 四环素类化合物 |
| EP2470500B1 (en) | 2009-08-28 | 2017-10-04 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| MX347919B (es) | 2010-05-12 | 2017-05-17 | Rempex Pharmaceuticals Inc * | Composiciones de tetraciclina. |
| CN103635456B (zh) * | 2011-07-26 | 2016-03-09 | 山东亨利医药科技有限责任公司 | 替加环素衍生物 |
| TR201902057T4 (tr) | 2012-08-31 | 2019-03-21 | Tetraphase Pharmaceuticals Inc | Tetrasiklin bileşikleri. |
| WO2015071299A2 (en) | 2013-11-12 | 2015-05-21 | Galenicum Health S.L. | Stable pharmaceutical compositions |
| MA46567A (fr) | 2016-10-19 | 2019-08-28 | Tetraphase Pharmaceuticals Inc | Formes cristallines de l'éravacycline |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3338963A (en) * | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
| US3579579A (en) * | 1968-04-18 | 1971-05-18 | American Cyanamid Co | Substituted 7- and/or 9-amino-6-demethyl-6-deoxytetracyclines |
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1992
- 1992-08-21 DK DK92114281T patent/DK0536515T3/da active
- 1992-08-21 DE DE200612000058 patent/DE122006000058I2/de active Active
- 1992-08-21 AT AT92114281T patent/ATE211128T1/de active
- 1992-08-21 PT PT92114281T patent/PT536515E/pt unknown
- 1992-08-21 ES ES92114281T patent/ES2168254T3/es not_active Expired - Lifetime
- 1992-08-21 EP EP92114281A patent/EP0536515B1/en not_active Expired - Lifetime
- 1992-08-21 DE DE69232302T patent/DE69232302T4/de not_active Expired - Lifetime
- 1992-08-21 SG SG1996003437A patent/SG52361A1/en unknown
- 1992-08-21 DE DE1992632302 patent/DE122006000058I1/de active Pending
- 1992-08-21 DE DE69232302A patent/DE69232302D1/de not_active Expired - Lifetime
- 1992-08-27 TW TW081106768A patent/TW275616B/zh not_active IP Right Cessation
- 1992-09-29 MX MX9205532A patent/MX9205532A/es unknown
- 1992-09-30 HU HU9203110A patent/HU219973B/hu unknown
- 1992-09-30 SK SK1149-99A patent/SK284826B6/sk not_active IP Right Cessation
- 1992-09-30 CZ CZ973093A patent/CZ309397A3/cs not_active IP Right Cessation
- 1992-09-30 CZ CS922984A patent/CZ284159B6/cs not_active IP Right Cessation
- 1992-09-30 SK SK2984-92A patent/SK280837B6/sk not_active IP Right Cessation
- 1992-10-01 IL IL10332092A patent/IL103320A/en not_active IP Right Cessation
- 1992-10-01 IL IL11959092A patent/IL119590A/xx not_active IP Right Cessation
- 1992-10-01 NZ NZ244585A patent/NZ244585A/en not_active IP Right Cessation
- 1992-10-02 KR KR1019920018122A patent/KR100269072B1/ko not_active Expired - Lifetime
- 1992-10-02 PL PL92310717A patent/PL172282B1/pl unknown
- 1992-10-02 PL PL92310718A patent/PL175957B1/pl unknown
- 1992-10-02 PL PL92296143A patent/PL173311B1/pl unknown
- 1992-10-02 AU AU26183/92A patent/AU654049B2/en not_active Expired
- 1992-10-02 FI FI924454A patent/FI114911B/fi active Protection Beyond IP Right Term
- 1992-10-02 CA CA002079692A patent/CA2079692C/en not_active Expired - Lifetime
- 1992-10-02 ZA ZA927607A patent/ZA927607B/xx unknown
- 1992-10-02 NO NO923857A patent/NO301472B1/no not_active IP Right Cessation
- 1992-10-02 PL PL92310719A patent/PL176333B1/pl unknown
- 1992-10-03 CN CN92112130A patent/CN1048240C/zh not_active Expired - Lifetime
- 1992-10-05 JP JP28811492A patent/JP3186863B2/ja not_active Expired - Lifetime
-
1995
- 1995-04-28 HU HU95P/P00116P patent/HU211172A9/hu active Protection Beyond IP Right Term
-
1996
- 1996-11-10 IL IL11959096A patent/IL119590A0/xx unknown
-
1997
- 1997-05-12 BR BR1100853-9A patent/BR1100853A/pt active IP Right Grant
-
2004
- 2004-06-25 CL CL200401623A patent/CL2004001623A1/es unknown
-
2006
- 2006-10-11 LU LU91279C patent/LU91279I2/fr unknown
- 2006-10-23 NL NL300244C patent/NL300244I1/nl unknown
- 2006-11-15 NO NO2006015C patent/NO2006015I2/no unknown
-
2017
- 2017-08-01 NO NO2017037C patent/NO2017037I2/no unknown
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