CA2721399A1 - Substituted tetracycline compounds - Google Patents
Substituted tetracycline compounds Download PDFInfo
- Publication number
- CA2721399A1 CA2721399A1 CA2721399A CA2721399A CA2721399A1 CA 2721399 A1 CA2721399 A1 CA 2721399A1 CA 2721399 A CA2721399 A CA 2721399A CA 2721399 A CA2721399 A CA 2721399A CA 2721399 A1 CA2721399 A1 CA 2721399A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- heterocyclic
- alkenyl
- alkynyl
- 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.)
- Abandoned
Links
- -1 tetracycline compounds Chemical class 0.000 title claims abstract description 324
- 239000004098 Tetracycline Substances 0.000 title claims abstract description 172
- 235000019364 tetracycline Nutrition 0.000 title claims abstract description 171
- 229960002180 tetracycline Drugs 0.000 title claims abstract description 136
- 229930101283 tetracycline Natural products 0.000 title claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 61
- 208000015181 infectious disease Diseases 0.000 claims abstract description 42
- 244000005700 microbiome Species 0.000 claims abstract description 38
- 125000003118 aryl group Chemical group 0.000 claims description 180
- 125000000217 alkyl group Chemical group 0.000 claims description 168
- 125000000623 heterocyclic group Chemical group 0.000 claims description 156
- 229910052739 hydrogen Inorganic materials 0.000 claims description 154
- 239000001257 hydrogen Substances 0.000 claims description 153
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 147
- 125000000304 alkynyl group Chemical group 0.000 claims description 145
- 125000003342 alkenyl group Chemical group 0.000 claims description 143
- 125000003545 alkoxy group Chemical group 0.000 claims description 130
- 229910052736 halogen Inorganic materials 0.000 claims description 129
- 150000002367 halogens Chemical group 0.000 claims description 128
- 125000002252 acyl group Chemical group 0.000 claims description 125
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 125
- 150000002431 hydrogen Chemical group 0.000 claims description 125
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 123
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 120
- 150000003568 thioethers Chemical group 0.000 claims description 120
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 119
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 48
- 150000002148 esters Chemical class 0.000 claims description 32
- 125000001931 aliphatic group Chemical group 0.000 claims description 29
- 239000000651 prodrug Chemical group 0.000 claims description 27
- 229940002612 prodrug Drugs 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 208000035143 Bacterial infection Diseases 0.000 claims description 17
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 241000588724 Escherichia coli Species 0.000 claims description 5
- 229940072172 tetracycline antibiotic Drugs 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 124
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 83
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 54
- 150000003522 tetracyclines Chemical class 0.000 description 45
- 229940040944 tetracyclines Drugs 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical class C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 229950000614 sancycline Drugs 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 238000002953 preparative HPLC Methods 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 229910019142 PO4 Inorganic materials 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 125000003282 alkyl amino group Chemical group 0.000 description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 10
- 150000002430 hydrocarbons Chemical group 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 10
- 239000010452 phosphate Substances 0.000 description 10
- 239000001632 sodium acetate Substances 0.000 description 10
- 235000017281 sodium acetate Nutrition 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- 125000004947 alkyl aryl amino group Chemical group 0.000 description 9
- 125000002877 alkyl aryl group Chemical group 0.000 description 9
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 9
- 125000001769 aryl amino group Chemical group 0.000 description 9
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 125000004663 dialkyl amino group Chemical group 0.000 description 9
- 125000004986 diarylamino group Chemical group 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 8
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 8
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 8
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 125000005129 aryl carbonyl group Chemical group 0.000 description 8
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 8
- 125000005110 aryl thio group Chemical group 0.000 description 8
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
- 150000007942 carboxylates Chemical class 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000012153 distilled water Substances 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 8
- 150000003467 sulfuric acid derivatives Chemical group 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- 238000006069 Suzuki reaction reaction Methods 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 description 6
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- 229960004023 minocycline Drugs 0.000 description 6
- 235000019366 oxytetracycline Nutrition 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 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 5
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 5
- 239000004099 Chlortetracycline Substances 0.000 description 5
- 206010017533 Fungal infection Diseases 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000031888 Mycoses Diseases 0.000 description 5
- 239000004100 Oxytetracycline Substances 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 125000005907 alkyl ester group Chemical group 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 5
- 229960004475 chlortetracycline Drugs 0.000 description 5
- 235000019365 chlortetracycline Nutrition 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 229960000625 oxytetracycline Drugs 0.000 description 5
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- FMTDIUIBLCQGJB-UHFFFAOYSA-N Demethylchlortetracyclin Natural products C1C2C(O)C3=C(Cl)C=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O FMTDIUIBLCQGJB-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000030852 Parasitic disease Diseases 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 208000036142 Viral infection Diseases 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline 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)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 4
- 229960002398 demeclocycline Drugs 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229940042016 methacycline Drugs 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[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 IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 3
- 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 3
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 description 3
- SHENXRCDBJGWNU-GOSISDBHSA-N 6-(1,3-benzothiazol-6-ylamino)-4-(cyclopropylamino)-n-[(2r)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound CC(C)(O)[C@H](F)CNC(=O)C1=CN=C(NC=2C=C3SC=NC3=CC=2)C=C1NC1CC1 SHENXRCDBJGWNU-GOSISDBHSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010034972 Photosensitivity reaction Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 125000002723 alicyclic group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
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Classifications
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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
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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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
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US4477308P | 2008-04-14 | 2008-04-14 | |
| US61/044,773 | 2008-04-14 | ||
| PCT/US2009/002344 WO2009128913A1 (en) | 2008-04-14 | 2009-04-14 | Substituted tetracycline compounds |
Publications (1)
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|---|---|
| CA2721399A1 true CA2721399A1 (en) | 2009-10-22 |
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| EP (1) | EP2276342A4 (cg-RX-API-DMAC7.html) |
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| PE (1) | PE20110069A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009128913A1 (cg-RX-API-DMAC7.html) |
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| CN103040773A (zh) | 2003-07-25 | 2013-04-17 | 沃纳奇尔科特有限责任公司 | 多西环素金属络合物固体剂型 |
| NZ556582A (en) * | 2005-01-21 | 2010-12-24 | Warner Chilcott Co Llc | A tetracycline metal complex in a solid dosage form |
| US20090253660A1 (en) | 2008-03-05 | 2009-10-08 | Paratek Pharmaceuticals, Inc. | Minocycline Compounds and Methods of Use Thereof |
| CN105367440A (zh) | 2008-08-08 | 2016-03-02 | 四相制药公司 | C7-氟取代的四环素化合物 |
| CA2761241C (en) | 2009-05-08 | 2018-02-27 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| WO2011025982A2 (en) | 2009-08-28 | 2011-03-03 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| CA2874640A1 (en) * | 2012-05-30 | 2013-12-05 | Paratek Pharmaceuticals, Inc. | 7-disubstituted-phenyl tetracycline derivatives |
| DK2890673T3 (en) | 2012-08-31 | 2019-03-18 | Tetraphase Pharmaceuticals Inc | tetracycline |
| DK3529236T3 (da) | 2016-10-19 | 2024-05-13 | Tetraphase Pharmaceuticals Inc | Krystalformer af eravacyclin |
| MX2019005070A (es) | 2016-11-01 | 2019-09-23 | Paratek Pharm Innc | Compuestos de 9-aminometil minociclina y su uso en el tratamiento de neumonía bacteriana adquirida en la comunidad (cabp). |
| US20230113011A1 (en) * | 2020-03-13 | 2023-04-13 | Cmtx Biotech Inc. | Methods of treating illnesses caused by coronavirus, swine flu and avian flu |
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| US2990331A (en) * | 1956-11-23 | 1961-06-27 | Pfizer & Co C | Stable solutions of salts of tetracyclines for parenteral administration |
| US2980584A (en) * | 1957-10-29 | 1961-04-18 | Pfizer & Co C | Parenteral magnesium oxytetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3062717A (en) * | 1958-12-11 | 1962-11-06 | Pfizer & Co C | Intramuscular calcium tetracycline acetic or lactic acid carboxamide vehicle preparation |
| US3165531A (en) * | 1962-03-08 | 1965-01-12 | Pfizer & Co C | 13-substituted-6-deoxytetracyclines and process utilizing the same |
| US3454697A (en) * | 1965-06-08 | 1969-07-08 | American Cyanamid Co | Tetracycline antibiotic compositions for oral use |
| NL6607516A (cg-RX-API-DMAC7.html) * | 1966-05-31 | 1967-12-01 | ||
| DE1767891C3 (de) * | 1968-06-28 | 1980-10-30 | Pfizer | Verfahren zur Herstellung von wäßrigen arzneilichen Lösungen für die parenterale, perorale und lokale Anwendung mit einem Gehalt an einem Tetracyclinderivat |
| US3957980A (en) * | 1972-10-26 | 1976-05-18 | Pfizer Inc. | Doxycycline parenteral compositions |
| DE2442829A1 (de) * | 1974-09-06 | 1976-03-18 | Merck Patent Gmbh | Tetracyclische verbindungen und verfahren zu ihrer herstellung |
| US4018889A (en) * | 1976-01-02 | 1977-04-19 | Pfizer Inc. | Oxytetracycline compositions |
| US4126680A (en) * | 1977-04-27 | 1978-11-21 | Pfizer Inc. | Tetracycline antibiotic compositions |
| US4806529A (en) * | 1982-11-18 | 1989-02-21 | Trustees Of Tufts College, Tufts University | Tetracycline activity enhancement |
| US5064821A (en) * | 1982-11-18 | 1991-11-12 | Trustees Of Tufts College | Method and compositions for overcoming tetracycline resistance within living cells |
| US5589470A (en) * | 1990-02-26 | 1996-12-31 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| US4806372A (en) * | 1985-02-15 | 1989-02-21 | Georgia Oil & Gas Co., Inc. | Nitrite-free-curing of bacon and product thereof |
| US6756365B2 (en) * | 1991-11-06 | 2004-06-29 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
| IL137445A0 (en) * | 1998-01-23 | 2001-07-24 | Tufts College | Pharmaceutically active compounds and methods of use thereof |
| US6256365B1 (en) * | 1999-08-16 | 2001-07-03 | Analogic Corporation | Apparatus and method for reconstruction of images in a computed tomography system using oblique slices |
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-
2009
- 2009-04-14 US US12/423,718 patent/US20100022483A1/en not_active Abandoned
- 2009-04-14 WO PCT/US2009/002344 patent/WO2009128913A1/en not_active Ceased
- 2009-04-14 CA CA2721399A patent/CA2721399A1/en not_active Abandoned
- 2009-04-14 AU AU2009236631A patent/AU2009236631A1/en not_active Abandoned
- 2009-04-14 JP JP2011505019A patent/JP2011517697A/ja active Pending
- 2009-04-14 EP EP09732861A patent/EP2276342A4/en not_active Withdrawn
-
2010
- 2010-04-14 PE PE2010000229A patent/PE20110069A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| US20100022483A1 (en) | 2010-01-28 |
| WO2009128913A1 (en) | 2009-10-22 |
| PE20110069A1 (es) | 2011-01-31 |
| EP2276342A1 (en) | 2011-01-26 |
| EP2276342A4 (en) | 2012-02-22 |
| AU2009236631A1 (en) | 2009-10-22 |
| JP2011517697A (ja) | 2011-06-16 |
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