JP2005505588A - テトラサイクリン誘導体、及びそれを使用する方法 - Google Patents
テトラサイクリン誘導体、及びそれを使用する方法 Download PDFInfo
- Publication number
- JP2005505588A JP2005505588A JP2003533853A JP2003533853A JP2005505588A JP 2005505588 A JP2005505588 A JP 2005505588A JP 2003533853 A JP2003533853 A JP 2003533853A JP 2003533853 A JP2003533853 A JP 2003533853A JP 2005505588 A JP2005505588 A JP 2005505588A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- doxycycline
- product
- solution
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000004098 Tetracycline Substances 0.000 title claims description 65
- 235000019364 tetracycline Nutrition 0.000 title claims description 64
- 229960002180 tetracycline Drugs 0.000 title claims description 60
- 229930101283 tetracycline Natural products 0.000 title claims description 59
- 150000003522 tetracyclines Chemical class 0.000 title description 52
- 238000000034 method Methods 0.000 title description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 230000012010 growth Effects 0.000 claims abstract description 20
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- -1 tetracycline compound Chemical class 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 241000894006 Bacteria Species 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 229930194542 Keto Natural products 0.000 claims description 2
- 125000000468 ketone 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
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 11
- 229910004013 NO 2 Inorganic materials 0.000 claims 11
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 10
- 229910052799 carbon Inorganic materials 0.000 claims 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 244000005700 microbiome Species 0.000 abstract description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 182
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
- 239000000047 product Substances 0.000 description 102
- 229960003722 doxycycline Drugs 0.000 description 95
- 239000000243 solution Substances 0.000 description 83
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 65
- 239000000203 mixture Substances 0.000 description 60
- 238000003756 stirring Methods 0.000 description 59
- 239000007787 solid Substances 0.000 description 58
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- 238000012360 testing method Methods 0.000 description 31
- 239000000706 filtrate Substances 0.000 description 23
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 22
- 239000003054 catalyst Substances 0.000 description 20
- 238000010790 dilution Methods 0.000 description 20
- 239000012895 dilution Substances 0.000 description 20
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
- 229910052763 palladium Inorganic materials 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 14
- 229960004023 minocycline Drugs 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000004323 potassium nitrate Substances 0.000 description 11
- 235000010333 potassium nitrate Nutrition 0.000 description 11
- FZUJWWOKDIGOKH-UHFFFAOYSA-N sulfuric acid hydrochloride Chemical compound Cl.OS(O)(=O)=O FZUJWWOKDIGOKH-UHFFFAOYSA-N 0.000 description 11
- 102000008186 Collagen Human genes 0.000 description 10
- 108010035532 Collagen Proteins 0.000 description 10
- 229920001436 collagen Polymers 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 239000012954 diazonium Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 6
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 6
- 102100030416 Stromelysin-1 Human genes 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 230000000845 anti-microbial effect Effects 0.000 description 6
- 150000001540 azides Chemical class 0.000 description 6
- 239000001110 calcium chloride Substances 0.000 description 6
- 229910001628 calcium chloride Inorganic materials 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 230000011382 collagen catabolic process Effects 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 5
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 5
- 102100030417 Matrilysin Human genes 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000036555 skin type Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 229940040944 tetracyclines Drugs 0.000 description 5
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 4
- 108010076119 Caseins Proteins 0.000 description 4
- 102000011632 Caseins Human genes 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 4
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 101000990912 Homo sapiens Matrilysin Proteins 0.000 description 4
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 4
- 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 description 4
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 4
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 4
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 230000009545 invasion Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 229950000614 sancycline Drugs 0.000 description 4
- 238000003345 scintillation counting Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- XCCHQGIGHCRZOS-KBKZQPOHSA-N (4as,5as,6s,12ar)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical class C1=CC=C2[C@@](C)(O)[C@@H](C[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)C3)(O)C3=O)C3=C(O)C2=C1O XCCHQGIGHCRZOS-KBKZQPOHSA-N 0.000 description 3
- IQIPCMYBFDOLBO-IRDJJEOVSA-N (4s,4as,5ar,12ar)-9-amino-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=C(N)C(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O IQIPCMYBFDOLBO-IRDJJEOVSA-N 0.000 description 3
- PTNZGHXUZDHMIQ-UHFFFAOYSA-N 4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C)C(C(O)C3C(C(O)=C(C(N)=O)C(=O)C3N(C)C)(O)C3=O)C3=C(O)C2=C1O PTNZGHXUZDHMIQ-UHFFFAOYSA-N 0.000 description 3
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 0 C[C@@]([C@@](*)[C@](*12)[C@](*)C(*)=C(C)C1=O)(C(*)(*)c(c(C)cc(*)c1O)c1C1=O)C1=C2O Chemical compound C[C@@]([C@@](*)[C@](*12)[C@](*)C(*)=C(C)C1=O)(C(*)(*)c(c(C)cc(*)c1O)c1C1=O)C1=C2O 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 3
- 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 description 3
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229960004082 doxycycline hydrochloride Drugs 0.000 description 3
- 239000008098 formaldehyde solution Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000000611 regression analysis Methods 0.000 description 3
- MTCQOMXDZUULRV-ADOAZJKMSA-N (4s,4as,5ar,12ar)-4-(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O MTCQOMXDZUULRV-ADOAZJKMSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 238000009631 Broth culture Methods 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 241000219061 Rheum Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000006491 bone marrow cancer Diseases 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000013100 final test Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 235000021247 β-casein Nutrition 0.000 description 2
- DHPRQBPJLMKORJ-XRZQSNOTSA-N (4r,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O DHPRQBPJLMKORJ-XRZQSNOTSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- LTNUSYNQZJZUSY-UHFFFAOYSA-N 3,3-dimethylbutanal Chemical compound CC(C)(C)CC=O LTNUSYNQZJZUSY-UHFFFAOYSA-N 0.000 description 1
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- VFTOHJFKIJLYKN-UHFFFAOYSA-N 7-nitro-9h-fluoren-2-ol Chemical group [O-][N+](=O)C1=CC=C2C3=CC=C(O)C=C3CC2=C1 VFTOHJFKIJLYKN-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000010975 Dystrophic epidermolysis bullosa Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 101150014058 MMP1 gene Proteins 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 1
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- AXIKDPDWFVPGOD-UHFFFAOYSA-O [7-(dimethylamino)phenothiazin-3-ylidene]-dimethylazanium;2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-10-ium-9-yl)benzoic acid Chemical compound C1=CC(=[N+](C)C)C=C2SC3=CC(N(C)C)=CC=C3N=C21.OC(=O)C1=CC=CC=C1C1=C(C=C(Br)C(O)=C2Br)C2=[O+]C2=C1C=C(Br)C(O)=C2Br AXIKDPDWFVPGOD-UHFFFAOYSA-O 0.000 description 1
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- IRJKSAIGIYODAN-ISLYRVAYSA-N benzyl (ne)-n-phenylmethoxycarbonyliminocarbamate Chemical compound C=1C=CC=CC=1COC(=O)/N=N/C(=O)OCC1=CC=CC=C1 IRJKSAIGIYODAN-ISLYRVAYSA-N 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- QQHZPQUHCAKSOL-UHFFFAOYSA-N butyl nitrate Chemical compound CCCCO[N+]([O-])=O QQHZPQUHCAKSOL-UHFFFAOYSA-N 0.000 description 1
- HSQIQSXOEZPHQW-UHFFFAOYSA-N butyl nitrite;nitrous acid Chemical compound ON=O.CCCCON=O HSQIQSXOEZPHQW-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical class C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- 108700004333 collagenase 1 Proteins 0.000 description 1
- 238000011613 copenhagen rat Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 208000004298 epidermolysis bullosa dystrophica Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229960002421 minocycline hydrochloride Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000003544 oxime group Chemical group 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940063650 terramycin Drugs 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
- A61K31/65—Tetracyclines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (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 |
|---|---|---|---|
| US32750201P | 2001-10-05 | 2001-10-05 | |
| PCT/US2002/031730 WO2003030819A2 (en) | 2001-10-05 | 2002-10-04 | Tetracycline derivatives and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005505588A true JP2005505588A (ja) | 2005-02-24 |
| JP2005505588A5 JP2005505588A5 (enExample) | 2006-09-07 |
Family
ID=23276795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003533853A Pending JP2005505588A (ja) | 2001-10-05 | 2002-10-04 | テトラサイクリン誘導体、及びそれを使用する方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US7214669B2 (enExample) |
| EP (1) | EP1439843A4 (enExample) |
| JP (1) | JP2005505588A (enExample) |
| CN (2) | CN1564690A (enExample) |
| AU (1) | AU2002341970B2 (enExample) |
| CA (1) | CA2462572C (enExample) |
| MY (1) | MY133403A (enExample) |
| NO (1) | NO20041272L (enExample) |
| RU (1) | RU2300380C2 (enExample) |
| WO (1) | WO2003030819A2 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007520482A (ja) * | 2004-01-15 | 2007-07-26 | 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 | テトラサイクリン化合物の芳香族ａ環誘導体 |
| JP2009537139A (ja) * | 2006-05-15 | 2009-10-29 | 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 | 置換されたテトラサイクリン化合物を用いて、遺伝子または遺伝子産物の発現を制御する方法 |
| JP2016130258A (ja) * | 2012-05-21 | 2016-07-21 | ディーシービー−ユーエスエー エルエルシーＤｃｂ−Ｕｓａ Ｌｌｃ | ゼブラフィッシュモデルを用いることにより薬物をスクリーニングする方法、及びこの方法によりスクリーニングされた化合物 |
| JP2024505700A (ja) * | 2021-02-03 | 2024-02-07 | スカイバイオ エルエルシー | 中枢神経系への低疎水性の生物活性薬に対して化学的にカップリングされたトランスポーター |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020132798A1 (en) | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| US7094806B2 (en) | 2000-07-07 | 2006-08-22 | Trustees Of Tufts College | 7, 8 and 9-substituted tetracycline compounds |
| WO2002072506A2 (en) * | 2001-03-13 | 2002-09-19 | Paratek Pharmaceuticals, Inc. | 7-pyrollyl tetracycline compounds and methods of use thereof |
| EP2298732A1 (en) * | 2001-03-13 | 2011-03-23 | Paratek Pharmaceuticals, Inc. | 7,9-Substituted tetracycline compounds |
| RU2300380C2 (ru) * | 2001-10-05 | 2007-06-10 | Тетрадженекс Фармасьютикалс, Инк. | Производные тетрациклина и способы их применения |
| US20050026833A1 (en) * | 2001-11-08 | 2005-02-03 | Rabbani Shafaat Ahmed | PSP-94: use for treatment of hypercalcemia and bone metastasis |
| EP2311797A1 (en) * | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| WO2004038000A2 (en) * | 2002-10-24 | 2004-05-06 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
| US20060287283A1 (en) * | 2003-07-09 | 2006-12-21 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
| EP1648859B1 (en) * | 2003-07-09 | 2013-02-27 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| US8012950B2 (en) * | 2003-08-29 | 2011-09-06 | Wisconsin Alumni Research Foundation | Method to diagnose and treat degenerative joint disease |
| CN101027279B (zh) * | 2004-05-21 | 2013-03-27 | 哈佛大学校长及研究员协会 | 四环素及其类似物的合成 |
| CA2585418A1 (en) | 2004-10-25 | 2006-05-04 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| EP1848685A1 (en) | 2005-02-04 | 2007-10-31 | Paratek Pharmaceuticals, Inc. | 11a, 12-derivatives of tetracycline compounds |
| AR057032A1 (es) * | 2005-05-27 | 2007-11-14 | Wyeth Corp | Tigeciclina y metodos de preparacion |
| AR057033A1 (es) * | 2005-05-27 | 2007-11-14 | Wyeth Corp | Tigeciclina y metodos para preparar 9-nitrominociclina |
| AR057324A1 (es) * | 2005-05-27 | 2007-11-28 | Wyeth Corp | Tigeciclina y metodos para preparar 9-aminominociclina |
| AU2007235279B2 (en) * | 2006-04-07 | 2012-12-06 | President And Fellows Of Harvard College | Synthesis of tetracyclines and analogues thereof |
| US7763735B2 (en) * | 2006-10-11 | 2010-07-27 | President And Fellows Of Harvard College | Synthesis of enone intermediate |
| US8440646B1 (en) | 2006-10-11 | 2013-05-14 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of Bacillus anthracis infections |
| WO2010126607A2 (en) | 2009-04-30 | 2010-11-04 | President And Fellows Of Harvard College | Synthesis of tetracyclines and intermediates thereto |
| SI2327676T1 (sl) * | 2009-11-26 | 2014-07-31 | Sandoz Ag | Reakcije organskih spojin z nizkimi količinami vodika |
| US20120329761A1 (en) * | 2010-03-10 | 2012-12-27 | University Health Network | Use of tigecycline for treatment of cancer |
| CN102631356B (zh) * | 2012-04-11 | 2014-03-12 | 广州市东来生物科技有限公司 | 4-去二甲氨基四环素衍生物在抗幽门螺旋杆菌方面的用途 |
| MA40836A (fr) | 2014-10-23 | 2017-08-29 | Tetraphase Pharmaceuticals Inc | Procédures de semi-synthèse |
| US11098073B2 (en) | 2017-04-20 | 2021-08-24 | Oxford University Innovation Limited | Triphenylphosphonium-tethered tetracyclines for use in treating cancer |
| CN110156624B (zh) * | 2019-05-29 | 2022-03-08 | 河北冀衡药业股份有限公司 | 一种米诺环素及其衍生物的合成方法 |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1063598B (de) * | 1957-02-14 | 1959-08-20 | Hoechst Ag | Verfahren zur Herstellung von wasserloeslichen Derivaten der Tetracycline |
| DE1088481B (de) * | 1958-01-29 | 1960-09-08 | American Cyanamid Co | Verfahren zur Herstellung neuer Verbindungen der Tetracyclinreihe |
| US3104240A (en) * | 1958-08-18 | 1963-09-17 | Bristol Myers Co | Mannich bases of tetracycline antibiotics |
| US2997471A (en) * | 1958-08-18 | 1961-08-22 | Bristol Myers Co | Tetracycline derivatives |
| US3026284A (en) * | 1959-05-13 | 1962-03-20 | Westinghouse Electric Corp | Process of treating a thermoplastic amine-aldehyde resin with a thermosetting additive and product obtained therefrom |
| US3029284A (en) * | 1960-09-14 | 1962-04-10 | Pfizer & Co C | Nu-dealkylation of carboxamido-nu-alkyltetracycline and its analogs |
| US3338963A (en) * | 1960-10-28 | 1967-08-29 | American Cyanamid Co | Tetracycline compounds |
| US3509184A (en) * | 1961-08-18 | 1970-04-28 | Pfizer & Co C | Anthracyclidine-acetic acid derivatives |
| US3772363A (en) * | 1961-08-18 | 1973-11-13 | Pfizer | 3,4,10-trioxo octahydroanthracene-2-aminoacetic acids and derivatives thereof |
| US3829453A (en) * | 1961-08-18 | 1974-08-13 | Pfizer | Octahydroanthracene-2-aminoacetic acids and esters and mixed anhydrides thereof |
| US3502696A (en) * | 1961-08-18 | 1970-03-24 | Pfizer & Co C | Antibacterial agents |
| US3145228A (en) * | 1962-09-06 | 1964-08-18 | Pfizer & Co C | 5-alkoxy-and 5-benzyloxy-tetracycline, derivatives and analogues thereof |
| US3265732A (en) * | 1964-02-28 | 1966-08-09 | American Cyanamid Co | Novel 5alpha, 6-anhydrotetracyclines |
| US3609188A (en) * | 1964-10-29 | 1971-09-28 | American Cyanamid Co | 4-dedimethylamino-4-substituted-amino-6-demethyltetracyclines |
| US3326761A (en) * | 1964-11-16 | 1967-06-20 | Pfizer & Co C | 6-demethyl-6-deoxytetracycline, anti-tumor antibiotic |
| US3345370A (en) * | 1965-03-16 | 1967-10-03 | American Cyanamid Co | 4-(n-mono-substituted) hydrazones of 4-dedimethylamino-4-oxo-tetracycline |
| US3388162A (en) * | 1966-03-14 | 1968-06-11 | American Cyanamid Co | 7-and/or 9-nitro or amino tetracyclines |
| US3515731A (en) * | 1966-06-17 | 1970-06-02 | Pfizer & Co C | Antibacterial agents |
| US3849493A (en) * | 1966-08-01 | 1974-11-19 | Pfizer | D-ring substituted 6-deoxytetracyclines |
| US3345410A (en) * | 1966-12-01 | 1967-10-03 | American Cyanamid Co | Substituted 7- and/or 9-amino tetracyclines |
| US3502660A (en) * | 1967-01-12 | 1970-03-24 | Pfizer & Co C | 2-((5'-(3' and/or 4'-substituted)isoxazoyl) methylidene)-3,4,10-trioxo-1,2,3,4,4a,9,9a,10-octahydroanthracenes |
| FR1520600A (fr) * | 1967-02-27 | 1968-04-12 | Snecma | Perfectionnements aux turbo-machines à flux axial, et en particulier aux compresseurs axiaux à deux rotors imbriqués contrarotatifs |
| US3824285A (en) * | 1967-09-13 | 1974-07-16 | Pfizer | 4-oxo-4-dedimethylaminotetracycline-4,6-hemiketals |
| US3622627A (en) * | 1967-09-13 | 1971-11-23 | Pfizer | 4-dedimethylaminatetracycline and 5a, 6-anhydro derivatives thereof |
| US4666897A (en) * | 1983-12-29 | 1987-05-19 | Research Foundation Of State University | Inhibition of mammalian collagenolytic enzymes by tetracyclines |
| US4925833A (en) * | 1983-12-29 | 1990-05-15 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis |
| USRE34656E (en) | 1983-12-29 | 1994-07-05 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of bone deficiency |
| US4704383A (en) * | 1983-12-29 | 1987-11-03 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| US4935412A (en) * | 1983-12-29 | 1990-06-19 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| US5122519A (en) * | 1989-06-27 | 1992-06-16 | American Cyanamid Company | Stable, cosmetically acceptable topical gel formulation and method of treatment for acne |
| US5045538A (en) * | 1990-06-28 | 1991-09-03 | The Research Foundation Of State University Of New York | Inhibition of wasting and protein degradation of mammalian muscle by tetracyclines |
| US5776898A (en) * | 1991-05-14 | 1998-07-07 | Dana-Farber Cancer Institute | Method for treating a tumor with a chemotherapeutic agent |
| US5494903A (en) * | 1991-10-04 | 1996-02-27 | American Cyanamid Company | 7-substituted-9-substituted amino-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 |
| US5442059A (en) * | 1992-08-13 | 1995-08-15 | American Cyanamid Company | 9-[(substituted glycyl)amido)]-6-demethyl-6-deoxytetracyclines |
| CA2103189C (en) * | 1992-11-17 | 2005-05-03 | Lorne M. Golub | Tetracyclines including non-antimicrobial chemically-modified tetracyclines inhibit excessive collagen crosslinking during diabetes |
| US5834450A (en) * | 1994-02-17 | 1998-11-10 | Pfizer Inc. | 9- (substituted amino) -alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics |
| EP0733369A1 (en) * | 1995-03-23 | 1996-09-25 | Stichting REGA V.Z.W. | Protease inhibitors, a DNA construct for the expression of a protease and a process for measuring proteases and/or protease inhibitors |
| US5837696A (en) * | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
| US6277061B1 (en) * | 1998-03-31 | 2001-08-21 | The Research Foundation Of State University Of New York | Method of inhibiting membrane-type matrix metalloproteinase |
| US6506740B1 (en) * | 1998-11-18 | 2003-01-14 | Robert A. Ashley | 4-dedimethylaminotetracycline derivatives |
| ES2272097T3 (es) * | 1998-11-18 | 2007-04-16 | Collagenex Pharmaceuticals, Inc. | Nuevos derivados de 4-desdimetilaminotetraciclina. |
| DE60129116T2 (de) * | 2000-03-31 | 2008-03-13 | Trustees Of Tufts College, Medford | 7- und 9-carbamat, harnstoff, thioharnstoff, thiocarbamat und heteroaryl-amino substituierte tetracyclinverbindungen |
| RU2300380C2 (ru) * | 2001-10-05 | 2007-06-10 | Тетрадженекс Фармасьютикалс, Инк. | Производные тетрациклина и способы их применения |
-
2002
- 2002-10-04 RU RU2004109986/14A patent/RU2300380C2/ru not_active IP Right Cessation
- 2002-10-04 AU AU2002341970A patent/AU2002341970B2/en not_active Ceased
- 2002-10-04 CN CNA028197224A patent/CN1564690A/zh active Pending
- 2002-10-04 CA CA002462572A patent/CA2462572C/en not_active Expired - Fee Related
- 2002-10-04 US US10/264,454 patent/US7214669B2/en not_active Expired - Fee Related
- 2002-10-04 EP EP02776131A patent/EP1439843A4/en not_active Withdrawn
- 2002-10-04 MY MYPI20023717A patent/MY133403A/en unknown
- 2002-10-04 JP JP2003533853A patent/JP2005505588A/ja active Pending
- 2002-10-04 WO PCT/US2002/031730 patent/WO2003030819A2/en not_active Ceased
- 2002-10-04 CN CNA2006100992267A patent/CN1961885A/zh active Pending
-
2004
- 2004-03-26 NO NO20041272A patent/NO20041272L/no not_active Application Discontinuation
-
2005
- 2005-03-09 US US11/076,276 patent/US20050267079A1/en not_active Abandoned
-
2007
- 2007-02-11 US US11/673,589 patent/US20070142338A1/en not_active Abandoned
- 2007-02-27 US US11/679,744 patent/US20070149488A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007520482A (ja) * | 2004-01-15 | 2007-07-26 | 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 | テトラサイクリン化合物の芳香族ａ環誘導体 |
| JP2009537139A (ja) * | 2006-05-15 | 2009-10-29 | 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 | 置換されたテトラサイクリン化合物を用いて、遺伝子または遺伝子産物の発現を制御する方法 |
| JP2016130258A (ja) * | 2012-05-21 | 2016-07-21 | ディーシービー−ユーエスエー エルエルシーＤｃｂ−Ｕｓａ Ｌｌｃ | ゼブラフィッシュモデルを用いることにより薬物をスクリーニングする方法、及びこの方法によりスクリーニングされた化合物 |
| JP2024505700A (ja) * | 2021-02-03 | 2024-02-07 | スカイバイオ エルエルシー | 中枢神経系への低疎水性の生物活性薬に対して化学的にカップリングされたトランスポーター |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2462572A1 (en) | 2003-04-17 |
| MY133403A (en) | 2007-11-30 |
| CA2462572C (en) | 2008-11-18 |
| CN1961885A (zh) | 2007-05-16 |
| CN1564690A (zh) | 2005-01-12 |
| RU2300380C2 (ru) | 2007-06-10 |
| US7214669B2 (en) | 2007-05-08 |
| EP1439843A4 (en) | 2007-01-03 |
| AU2002341970B2 (en) | 2008-02-14 |
| WO2003030819A2 (en) | 2003-04-17 |
| US20050267079A1 (en) | 2005-12-01 |
| RU2004109986A (ru) | 2005-02-20 |
| NO20041272L (no) | 2004-07-02 |
| WO2003030819A3 (en) | 2004-01-08 |
| EP1439843A2 (en) | 2004-07-28 |
| US20070149488A1 (en) | 2007-06-28 |
| US20040067912A1 (en) | 2004-04-08 |
| US20070142338A1 (en) | 2007-06-21 |
| US20050245491A9 (en) | 2005-11-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005505588A (ja) | テトラサイクリン誘導体、及びそれを使用する方法 | |
| AU2002341970A1 (en) | Tetracycline derivatives and methods of use thereof | |
| US5326759A (en) | 9-amino-7-(substituted)-6-demethyl-6-deoxytetracyclines | |
| CA2503446C (en) | Methods of using substituted tetracycline compounds to modulate rna | |
| EP1137410B1 (en) | Novel 4-dedimethyl aminotetracycline derivatives | |
| US6894036B2 (en) | 4-dedimethylaminotetracycline derivatives | |
| US20130029943A1 (en) | Methods of Preparing Substituted Tetracyclines with Transition Metal-Based Chemistries | |
| SK281871B6 (sk) | 6-demetyl-6-deoxytetracyklíny, spôsoby a medziprodukty na ich výrobu a farmaceutické prípravky na ich báze | |
| US20080177080A1 (en) | Oxazole derivatives of tetracyclines | |
| US6946453B2 (en) | 4-dedimethylaminotracycline derivatives | |
| US5998615A (en) | Anthracyclinone derivatives | |
| EP1894569A2 (en) | Tetracycline derivatives for treating cancer | |
| HK1101129A (en) | Use of tetracycline derivatives in the pharmacy | |
| JPH09100289A (ja) | 新規化合物ｆｒ１９０８９５、ｆｒ１９０８７２及びｆｒ１９０８７３、その製造方法およびその用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050905 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060719 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090818 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100216 |