JP6715772B2 - 12−epi−プロイロムチリン - Google Patents
12−epi−プロイロムチリン Download PDFInfo
- Publication number
- JP6715772B2 JP6715772B2 JP2016547848A JP2016547848A JP6715772B2 JP 6715772 B2 JP6715772 B2 JP 6715772B2 JP 2016547848 A JP2016547848 A JP 2016547848A JP 2016547848 A JP2016547848 A JP 2016547848A JP 6715772 B2 JP6715772 B2 JP 6715772B2
- Authority
- JP
- Japan
- Prior art keywords
- amino
- methyl
- acetyl
- epi
- desvinyl
- 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.)
- Expired - Fee Related
Links
- -1 -Carbamimidoyl Chemical group 0.000 claims description 583
- STZYTFJPGGDRJD-NHUWBDDWSA-N retapamulin Chemical group C([C@H]([C@@]1(C)[C@@H](C[C@@](C)(C=C)[C@@H](O)[C@@H]2C)OC(=O)CS[C@@H]3C[C@H]4CC[C@H](N4C)C3)C)C[C@]32[C@H]1C(=O)CC3 STZYTFJPGGDRJD-NHUWBDDWSA-N 0.000 claims description 270
- 229960002771 retapamulin Drugs 0.000 claims description 270
- OBUUFWIMEGVAQS-UHFFFAOYSA-N Pleuromutenol Natural products CC1C(O)C(C)(C=C)CC(O)C2(C)C(C)CCC31C2C(=O)CC3 OBUUFWIMEGVAQS-UHFFFAOYSA-N 0.000 claims description 253
- 150000001875 compounds Chemical class 0.000 claims description 246
- 125000000217 alkyl group Chemical group 0.000 claims description 214
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
- 125000003118 aryl group Chemical group 0.000 claims description 67
- 125000000623 heterocyclic group Chemical group 0.000 claims description 58
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
- 125000005842 heteroatom Chemical group 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- ZRZNJUXESFHSIO-VYTKZBNOSA-N pleuromutilin Chemical group C([C@H]([C@]1(C)[C@@H](C[C@@](C)(C=C)[C@@H](O)[C@@H]2C)OC(=O)CO)C)C[C@]32[C@H]1C(=O)CC3 ZRZNJUXESFHSIO-VYTKZBNOSA-N 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 229910052717 sulfur Inorganic materials 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 25
- ZRZNJUXESFHSIO-UHFFFAOYSA-N Pleuromutilin Natural products CC1C(O)C(C)(C=C)CC(OC(=O)CO)C2(C)C(C)CCC31C2C(=O)CC3 ZRZNJUXESFHSIO-UHFFFAOYSA-N 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 241000588724 Escherichia coli Species 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 241000894006 Bacteria Species 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 239000012453 solvate Chemical class 0.000 claims description 10
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 9
- 239000013543 active substance Substances 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 7
- 150000002430 hydrocarbons Chemical class 0.000 claims description 7
- 244000005700 microbiome Species 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000003725 azepanyl group Chemical group 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
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
- 239000000203 mixture Substances 0.000 description 156
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 235000019439 ethyl acetate Nutrition 0.000 description 101
- 238000000034 method Methods 0.000 description 88
- 239000011734 sodium Substances 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- 239000012074 organic phase Substances 0.000 description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 239000000243 solution Substances 0.000 description 46
- 239000007858 starting material Substances 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- 239000012267 brine Substances 0.000 description 38
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- 239000013078 crystal Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 239000000126 substance Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000008346 aqueous phase Substances 0.000 description 20
- 238000012512 characterization method Methods 0.000 description 20
- 239000003480 eluent Substances 0.000 description 20
- 238000000746 purification Methods 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 18
- 239000006260 foam Substances 0.000 description 17
- 238000004587 chromatography analysis Methods 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 12
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- 208000002874 Acne Vulgaris Diseases 0.000 description 7
- 239000007821 HATU Substances 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 206010000496 acne Diseases 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 6
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 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
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 description 5
- 230000000845 anti-microbial effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 5
- 239000000843 powder Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 241000605909 Fusobacterium Species 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 230000000640 hydroxylating effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 3
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 3
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 3
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 3
- 241000588921 Enterobacteriaceae Species 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- WNGBMUQXLKXBEA-UHFFFAOYSA-N S-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]piperidin-4-yl] ethanethioate Chemical compound CC(=O)SC1CCN(CC1)C(=O)CNC(=O)OC(C)(C)C WNGBMUQXLKXBEA-UHFFFAOYSA-N 0.000 description 3
- BKCPJEJZNWDJBV-UHFFFAOYSA-N SC1=CC=C(C=C1)CC(=O)NCCCNC(OC(C)(C)C)=O Chemical compound SC1=CC=C(C=C1)CC(=O)NCCCNC(OC(C)(C)C)=O BKCPJEJZNWDJBV-UHFFFAOYSA-N 0.000 description 3
- NWIOPXYGRALHGD-UHFFFAOYSA-N [4-(hydroxymethyl)-3-sulfanylphenyl]methanol Chemical compound OCC1=CC(=C(C=C1)CO)S NWIOPXYGRALHGD-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000005949 ozonolysis reaction Methods 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- FHGOQRMTDVEYSW-UHFFFAOYSA-N tert-butyl 4-acetylsulfanylazepane-1-carboxylate Chemical compound C(C)(=O)SC1CCN(CCC1)C(=O)OC(C)(C)C FHGOQRMTDVEYSW-UHFFFAOYSA-N 0.000 description 3
- MVZFCZBVGIAEPL-UHFFFAOYSA-N tert-butyl N-(4-iodophenyl)-N-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamate Chemical compound C(C)(C)(C)OC(N(C1=CC=C(C=C1)I)CCNC(=O)OC(C)(C)C)=O MVZFCZBVGIAEPL-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- RSUQHFURAUXZMD-UHFFFAOYSA-N 2,2,2-trifluoro-N-[3-(4-sulfanylphenyl)propyl]acetamide Chemical compound FC(C(=O)NCCCC1=CC=C(C=C1)S)(F)F RSUQHFURAUXZMD-UHFFFAOYSA-N 0.000 description 2
- HTVBDXZFFHRMTN-UHFFFAOYSA-N 2-(4-acetylsulfanylphenyl)acetic acid Chemical compound CC(=O)SC1=CC=C(CC(O)=O)C=C1 HTVBDXZFFHRMTN-UHFFFAOYSA-N 0.000 description 2
- STTRTNHPKHDOLC-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]propanoic acid Chemical compound C(C)(C)(C)OC(=O)NC(C(=O)O)CC1=CC=C(C=C1)CNC(=O)OC(C)(C)C STTRTNHPKHDOLC-UHFFFAOYSA-N 0.000 description 2
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
- JFLCHIVRKHRRTG-UHFFFAOYSA-N 2-chlorosulfonylterephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(S(Cl)(=O)=O)=C1 JFLCHIVRKHRRTG-UHFFFAOYSA-N 0.000 description 2
- FFHNZBHCEGONDG-UHFFFAOYSA-N 2-sulfanylterephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(S)=C1 FFHNZBHCEGONDG-UHFFFAOYSA-N 0.000 description 2
- RMBLTLXJGNILPG-UHFFFAOYSA-N 3-(4-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=C(C#N)C=C1 RMBLTLXJGNILPG-UHFFFAOYSA-N 0.000 description 2
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 2
- WXTPYQXMRLGPJW-UHFFFAOYSA-N 4-[3-[(2,2,2-trifluoroacetyl)amino]propyl]benzenesulfonyl chloride Chemical compound FC(F)(F)C(=O)NCCCC1=CC=C(S(Cl)(=O)=O)C=C1 WXTPYQXMRLGPJW-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- FOYCYOHOMTVNIX-UHFFFAOYSA-M 6-azidohexyl(triphenyl)phosphanium iodide Chemical compound [I-].N(=[N+]=[N-])CCCCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 FOYCYOHOMTVNIX-UHFFFAOYSA-M 0.000 description 2
- XOHYIMPPOJMBHL-UHFFFAOYSA-M 6-bromohexyl(triphenyl)phosphanium iodide Chemical compound [I-].BrCCCCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 XOHYIMPPOJMBHL-UHFFFAOYSA-M 0.000 description 2
- ZHPLCGQZGMTUID-UHFFFAOYSA-N 6-iodohexan-1-ol Chemical compound OCCCCCCI ZHPLCGQZGMTUID-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
- 241000588626 Acinetobacter baumannii Species 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- BJSKQQHVONOLMH-UHFFFAOYSA-N C(C)(C)(C)OC(=O)NCC1=CC=C(CNC(=O)C2=CC=C(C=C2)SC(C)=O)C=C1 Chemical compound C(C)(C)(C)OC(=O)NCC1=CC=C(CNC(=O)C2=CC=C(C=C2)SC(C)=O)C=C1 BJSKQQHVONOLMH-UHFFFAOYSA-N 0.000 description 2
- WSLMPMCMBIKIDT-UHFFFAOYSA-N C(C)(C)(C)OC(=O)NCCCNC(=O)C=1C=CC(=NC1)SSC1=CC=C(C=N1)C(=O)NCCCNC(OC(C)(C)C)=O Chemical compound C(C)(C)(C)OC(=O)NCCCNC(=O)C=1C=CC(=NC1)SSC1=CC=C(C=N1)C(=O)NCCCNC(OC(C)(C)C)=O WSLMPMCMBIKIDT-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- YDKYELRECSCAIL-UHFFFAOYSA-N CC(C)(C)OC(NCCCNC(CC(C=C1)=CC=C1[S+]=C(C)[O-])=O)=O Chemical compound CC(C)(C)OC(NCCCNC(CC(C=C1)=CC=C1[S+]=C(C)[O-])=O)=O YDKYELRECSCAIL-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000606161 Chlamydia Species 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 241000194031 Enterococcus faecium Species 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 2
- 241000606790 Haemophilus Species 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- 241000589989 Helicobacter Species 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000588655 Moraxella catarrhalis Species 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- DBVRLDXHGGUDAI-UHFFFAOYSA-N N-[(3-sulfanylphenyl)methyl]acetamide Chemical compound SC=1C=C(CNC(C)=O)C=CC1 DBVRLDXHGGUDAI-UHFFFAOYSA-N 0.000 description 2
- XENDJECXVBYRAN-UHFFFAOYSA-N N-[[3-[[3-(acetamidomethyl)phenyl]disulfanyl]phenyl]methyl]acetamide Chemical compound C(C)(=O)NCC=1C=C(C=CC1)SSC=1C=C(CNC(C)=O)C=CC1 XENDJECXVBYRAN-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- BTPCHZZJTIKTPR-UHFFFAOYSA-N S-(3-oxocyclohexyl) ethanethioate Chemical compound C(C)(=O)SC1CC(CCC1)=O BTPCHZZJTIKTPR-UHFFFAOYSA-N 0.000 description 2
- RZQYVDAYGGNRTH-UHFFFAOYSA-N S-(azepan-4-yl) ethanethioate Chemical compound N1CCC(CCC1)SC(C)=O RZQYVDAYGGNRTH-UHFFFAOYSA-N 0.000 description 2
- UMTVWIWOEPXWKK-UHFFFAOYSA-N S-[3-(2,2-difluoroethylamino)cyclohexyl] ethanethioate Chemical compound FC(CNC1CC(CCC1)SC(C)=O)F UMTVWIWOEPXWKK-UHFFFAOYSA-N 0.000 description 2
- VJRUNMJVNBOVMW-UHFFFAOYSA-N S-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclohexyl] ethanethioate Chemical compound C(C)(C)(C)OC(=O)NCC1CCC(CC1)SC(C)=O VJRUNMJVNBOVMW-UHFFFAOYSA-N 0.000 description 2
- HTPIGOIEJMAMEX-UHFFFAOYSA-N S-[5-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyridin-2-yl] ethanethioate Chemical compound C(C)(C)(C)OC(=O)NCC=1C=CC(=NC=1)SC(C)=O HTPIGOIEJMAMEX-UHFFFAOYSA-N 0.000 description 2
- BCHCNROROKRUFV-UHFFFAOYSA-N S-[[4-(azidomethyl)cyclohexyl]methyl] ethanethioate Chemical compound CC(=O)SCC1CCC(CN=[N+]=[N-])CC1 BCHCNROROKRUFV-UHFFFAOYSA-N 0.000 description 2
- HHDLMRLUSRQIHM-UHFFFAOYSA-N S-[[4-(methylsulfonyloxymethyl)cyclohexyl]methyl] ethanethioate Chemical compound CS(=O)(=O)OCC1CCC(CC1)CSC(C)=O HHDLMRLUSRQIHM-UHFFFAOYSA-N 0.000 description 2
- QZPFAAVBWGPYCR-UHFFFAOYSA-N SC1=CC=C(C=N1)C(=O)NCCCNC(OC(C)(C)C)=O Chemical compound SC1=CC=C(C=N1)C(=O)NCCCNC(OC(C)(C)C)=O QZPFAAVBWGPYCR-UHFFFAOYSA-N 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 2
- QOFPQHCKMBKEHP-UHFFFAOYSA-N [3-[[3-(aminomethyl)phenyl]disulfanyl]phenyl]methanamine Chemical compound NCC=1C=C(C=CC1)SSC=1C=C(CN)C=CC1 QOFPQHCKMBKEHP-UHFFFAOYSA-N 0.000 description 2
- GJBJOHZKXGTHQA-UHFFFAOYSA-N [3-[[3-(hydroxymethyl)phenyl]disulfanyl]phenyl]methanol Chemical compound OCC=1C=C(C=CC1)SSC=1C=C(C=CC1)CO GJBJOHZKXGTHQA-UHFFFAOYSA-N 0.000 description 2
- CLYCTEPNFJPDCT-UHFFFAOYSA-N [3-[[3-(methylsulfonyloxymethyl)phenyl]disulfanyl]phenyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC=1C=C(C=CC1)SSC=1C=C(COS(=O)(=O)C)C=CC1 CLYCTEPNFJPDCT-UHFFFAOYSA-N 0.000 description 2
- KXUXFJPOYNTCAS-UHFFFAOYSA-N [4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclohexyl] methanesulfonate Chemical compound CC(C)(C)OC(=O)NCC1CCC(OS(C)(=O)=O)CC1 KXUXFJPOYNTCAS-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- RWOKOVIIXPDBRJ-UHFFFAOYSA-N benzyl N-[[4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]phenyl]methyl]carbamate Chemical compound C(C)(C)(C)OC(NCCOC1=CC=C(C=C1)CNC(=O)OCC1=CC=CC=C1)=O RWOKOVIIXPDBRJ-UHFFFAOYSA-N 0.000 description 2
- DDULMAJJEKQKNM-UHFFFAOYSA-N benzyl n-[(4-hydroxyphenyl)methyl]carbamate Chemical compound C1=CC(O)=CC=C1CNC(=O)OCC1=CC=CC=C1 DDULMAJJEKQKNM-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 2
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 229940047650 haemophilus influenzae Drugs 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000006197 hydroboration reaction Methods 0.000 description 2
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- FCVOVMIYANJKKG-UHFFFAOYSA-N n-[(4-aminophenyl)methyl]-2,2,2-trifluoroacetamide Chemical compound NC1=CC=C(CNC(=O)C(F)(F)F)C=C1 FCVOVMIYANJKKG-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- LZIMZHBYBYQWJZ-UHFFFAOYSA-N s-(4-carbonochloridoylphenyl) ethanethioate Chemical compound CC(=O)SC1=CC=C(C(Cl)=O)C=C1 LZIMZHBYBYQWJZ-UHFFFAOYSA-N 0.000 description 2
- UMRBXDQQUOGAQM-UHFFFAOYSA-N s-piperidin-4-yl ethanethioate;hydrochloride Chemical compound Cl.CC(=O)SC1CCNCC1 UMRBXDQQUOGAQM-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- SJAKIGKVIJINMY-UHFFFAOYSA-N tert-butyl 4-acetylsulfanylpiperidine-1-carboxylate Chemical compound CC(=O)SC1CCN(C(=O)OC(C)(C)C)CC1 SJAKIGKVIJINMY-UHFFFAOYSA-N 0.000 description 2
- CRFSWDBNKHNGGA-UHFFFAOYSA-N tert-butyl 4-hydroxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)CC1 CRFSWDBNKHNGGA-UHFFFAOYSA-N 0.000 description 2
- WXGIMXRYMZMWQR-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxyazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(OS(C)(=O)=O)CC1 WXGIMXRYMZMWQR-UHFFFAOYSA-N 0.000 description 2
- WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 2
- PMLBUVZPRKXMOX-UHFFFAOYSA-N tert-butyl 4-oxoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)CC1 PMLBUVZPRKXMOX-UHFFFAOYSA-N 0.000 description 2
- ICMJQFXRAJTOGL-UHFFFAOYSA-N tert-butyl N-[1-amino-3-[4-(aminomethyl)phenyl]-1-oxopropan-2-yl]carbamate Chemical compound NC(C(CC1=CC=C(C=C1)CN)NC(OC(C)(C)C)=O)=O ICMJQFXRAJTOGL-UHFFFAOYSA-N 0.000 description 2
- ZYZYZSUBFAHRNR-UHFFFAOYSA-N tert-butyl N-[3-[[4-(aminomethyl)benzoyl]amino]propyl]carbamate Chemical compound NCC1=CC=C(C(=O)NCCCNC(OC(C)(C)C)=O)C=C1 ZYZYZSUBFAHRNR-UHFFFAOYSA-N 0.000 description 2
- NKAOZLAOYCNJBZ-UHFFFAOYSA-N tert-butyl n-[[4-(aminomethyl)-2-fluorophenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(CN)C=C1F NKAOZLAOYCNJBZ-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- 208000019206 urinary tract infection Diseases 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- IIPCTBAMTPCGJK-UHFFFAOYSA-N (3-sulfanylphenyl)methanol Chemical compound OCC1=CC=CC(S)=C1 IIPCTBAMTPCGJK-UHFFFAOYSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- BQTRMYJYYNQQGK-UHFFFAOYSA-N 1-(bromomethyl)-4-iodobenzene Chemical compound BrCC1=CC=C(I)C=C1 BQTRMYJYYNQQGK-UHFFFAOYSA-N 0.000 description 1
- OVRWUZYZECPJOB-UHFFFAOYSA-N 2,2-difluoroethanamine Chemical compound NCC(F)F OVRWUZYZECPJOB-UHFFFAOYSA-N 0.000 description 1
- JIVWEXNZENANHT-UHFFFAOYSA-N 2-(4-iodoanilino)ethylcarbamic acid Chemical compound OC(=O)NCCNC1=CC=C(I)C=C1 JIVWEXNZENANHT-UHFFFAOYSA-N 0.000 description 1
- ORXSLDYRYTVAPC-UHFFFAOYSA-N 2-(4-sulfanylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(S)C=C1 ORXSLDYRYTVAPC-UHFFFAOYSA-N 0.000 description 1
- RPTBUKFXLSZAKD-UHFFFAOYSA-N 2-bromoethylcarbamic acid Chemical compound OC(=O)NCCBr RPTBUKFXLSZAKD-UHFFFAOYSA-N 0.000 description 1
- ITHCSGCUQDMYAI-ZMIZWQJLSA-N 2-carboxy-D-arabinitol 1,5-bisphosphate Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@](O)(COP(O)(O)=O)C(O)=O ITHCSGCUQDMYAI-ZMIZWQJLSA-N 0.000 description 1
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- CERMXASDHWBOJI-UHFFFAOYSA-N 3-[(4-cyanobenzoyl)amino]propylcarbamic acid Chemical compound OC(=O)NCCCNC(=O)C1=CC=C(C#N)C=C1 CERMXASDHWBOJI-UHFFFAOYSA-N 0.000 description 1
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 1
- BFWYZZPDZZGSLJ-UHFFFAOYSA-N 4-(aminomethyl)aniline Chemical compound NCC1=CC=C(N)C=C1 BFWYZZPDZZGSLJ-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- RQJDUEKERVZLLU-UHFFFAOYSA-N 4-Hydroxybenzylamine Chemical compound NCC1=CC=C(O)C=C1 RQJDUEKERVZLLU-UHFFFAOYSA-N 0.000 description 1
- LNKHBRDWRIIROP-UHFFFAOYSA-N 4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]benzoic acid Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(C(O)=O)C=C1 LNKHBRDWRIIROP-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- ZUDCIPNZEZLOLJ-UHFFFAOYSA-N 4-acetylsulfanylbenzoic acid Chemical compound CC(=O)SC1=CC=C(C(O)=O)C=C1 ZUDCIPNZEZLOLJ-UHFFFAOYSA-N 0.000 description 1
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- RXQDBVWDABAAHL-UHFFFAOYSA-N 6-(phenylmethoxycarbonylamino)hexanoic acid Chemical compound OC(=O)CCCCCNC(=O)OCC1=CC=CC=C1 RXQDBVWDABAAHL-UHFFFAOYSA-N 0.000 description 1
- LXNSWDBBXHIYKY-UHFFFAOYSA-N 6-[(5-carbonochloridoylpyridin-2-yl)disulfanyl]pyridine-3-carbonyl chloride Chemical compound ClC(=O)C=1C=CC(=NC1)SSC1=CC=C(C=N1)C(=O)Cl LXNSWDBBXHIYKY-UHFFFAOYSA-N 0.000 description 1
- GSASOFRDSIKDSN-UHFFFAOYSA-N 6-[(5-carboxypyridin-2-yl)disulfanyl]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1SSC1=CC=C(C(O)=O)C=N1 GSASOFRDSIKDSN-UHFFFAOYSA-N 0.000 description 1
- JYYXVDYYEXMEJU-UHFFFAOYSA-N 6-amino-n,n-dimethylhexanamide Chemical compound CN(C)C(=O)CCCCCN JYYXVDYYEXMEJU-UHFFFAOYSA-N 0.000 description 1
- KKEGYNFNENTNGM-UHFFFAOYSA-M 6-hydroxyhexyl(triphenyl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCO)C1=CC=CC=C1 KKEGYNFNENTNGM-UHFFFAOYSA-M 0.000 description 1
- PWSJCBQLHHENIG-UHFFFAOYSA-N 6-sulfanylidene-1h-pyridine-3-carboxamide Chemical compound NC(=O)C=1C=CC(=S)NC=1 PWSJCBQLHHENIG-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241001135518 Acinetobacter lwoffii Species 0.000 description 1
- 241001464890 Anaerococcus prevotii Species 0.000 description 1
- 206010060968 Arthritis infective Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OBUUFWIMEGVAQS-JAFVRLMVSA-N C([C@H]([C@@]1(C)[C@H](O)C[C@@](C)(C=C)[C@@H](O)[C@@H]2C)C)C[C@]32[C@H]1C(=O)CC3 Chemical compound C([C@H]([C@@]1(C)[C@H](O)C[C@@](C)(C=C)[C@@H](O)[C@@H]2C)C)C[C@]32[C@H]1C(=O)CC3 OBUUFWIMEGVAQS-JAFVRLMVSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000588919 Citrobacter freundii Species 0.000 description 1
- 241001112696 Clostridia Species 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 241001657508 Eggerthella lenta Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 241000192016 Finegoldia magna Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000605952 Fusobacterium necrophorum Species 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 101001035951 Homo sapiens Hyaluronan-binding protein 2 Proteins 0.000 description 1
- 102100039238 Hyaluronan-binding protein 2 Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000036209 Intraabdominal Infections Diseases 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- VSUGTEXHJDXTIB-UHFFFAOYSA-N NCC1=CC=C(OCCNC(O)=O)C=C1 Chemical compound NCC1=CC=C(OCCNC(O)=O)C=C1 VSUGTEXHJDXTIB-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000588656 Neisseriaceae Species 0.000 description 1
- BXEFQPCKQSTMKA-UHFFFAOYSA-N OC(=O)C=[N+]=[N-] Chemical compound OC(=O)C=[N+]=[N-] BXEFQPCKQSTMKA-UHFFFAOYSA-N 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000351207 Peptoniphilus Species 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 241000192035 Peptostreptococcus anaerobius Species 0.000 description 1
- 241000222350 Pleurotus Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000605894 Porphyromonas Species 0.000 description 1
- 241001135211 Porphyromonas asaccharolytica Species 0.000 description 1
- 241001135217 Prevotella buccae Species 0.000 description 1
- 241001135262 Prevotella oris Species 0.000 description 1
- 102100021486 Protein S100-G Human genes 0.000 description 1
- 101710122252 Protein S100-G Proteins 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- QOVJCAUBERPZOH-UHFFFAOYSA-N S-[4-[[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]methyl]cyclohexyl] ethanethioate Chemical compound C(C)(C)(C)OC(=O)NCC(=O)NCC1CCC(CC1)SC(C)=O QOVJCAUBERPZOH-UHFFFAOYSA-N 0.000 description 1
- WANLBCLXESPMOA-UHFFFAOYSA-N SC1=CC=C(C=N1)CNC(O)=O Chemical compound SC1=CC=C(C=N1)CNC(O)=O WANLBCLXESPMOA-UHFFFAOYSA-N 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- CNTVUGYMAHTWKS-UHFFFAOYSA-N [4-(methylsulfonyloxymethyl)cyclohexyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCC(COS(C)(=O)=O)CC1 CNTVUGYMAHTWKS-UHFFFAOYSA-N 0.000 description 1
- HAUPIAJPYMWDJK-UHFFFAOYSA-M [I].[I-].N(=[N+]=[N-])CCCCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [I].[I-].N(=[N+]=[N-])CCCCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 HAUPIAJPYMWDJK-UHFFFAOYSA-M 0.000 description 1
- UATOFRZSCHRPBG-UHFFFAOYSA-N acetamide;hydrate Chemical compound O.CC(N)=O UATOFRZSCHRPBG-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003103 anti-anaerobic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 208000037815 bloodstream infection Diseases 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- 125000006448 cycloalkyl cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- JOPZIXGQUDHRNP-UHFFFAOYSA-N ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]propanoate Chemical compound C(C)(C)(C)OC(=O)NC(C(=O)OCC)CC1=CC=C(C=C1)CNC(=O)OC(C)(C)C JOPZIXGQUDHRNP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000011323 eye infectious disease Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- LFXAECSQJSRSTP-UHFFFAOYSA-N hydron;methyl carbamimidothioate;iodide Chemical compound I.CSC(N)=N LFXAECSQJSRSTP-UHFFFAOYSA-N 0.000 description 1
- KRZGKJJPEOUIBI-UHFFFAOYSA-N hydron;thiourea;iodide Chemical compound I.NC(S)=N KRZGKJJPEOUIBI-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000009027 insemination Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940116298 l- malic acid Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YQFIQNIOQYPOTP-JTQLQIEISA-N methyl (2s)-2-amino-3-(4-cyanophenyl)propanoate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(C#N)C=C1 YQFIQNIOQYPOTP-JTQLQIEISA-N 0.000 description 1
- AUVCCKINWBIXOP-UHFFFAOYSA-N methyl 3-(4-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)NC(C(=O)OC)CC1=CC=C(C#N)C=C1 AUVCCKINWBIXOP-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000006385 ozonation reaction Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940074571 peptostreptococcus anaerobius Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- AFNBMGLGYSGFEZ-UHFFFAOYSA-M potassium;ethanethioate Chemical compound [K+].CC([S-])=O AFNBMGLGYSGFEZ-UHFFFAOYSA-M 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- FAMJEPHYYIZVGP-UHFFFAOYSA-N tert-butyl N-[(6-sulfanylidene-1H-pyridin-3-yl)methyl]carbamate Chemical compound SC1=NC=C(C=C1)CNC(=O)OC(C)(C)C FAMJEPHYYIZVGP-UHFFFAOYSA-N 0.000 description 1
- KZQHRZHGSWJSJX-UHFFFAOYSA-N tert-butyl N-[1-amino-3-(4-cyanophenyl)-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CC1=CC=C(C=C1)C#N)C(N)=O KZQHRZHGSWJSJX-UHFFFAOYSA-N 0.000 description 1
- DQBPFCICGMBSPQ-UHFFFAOYSA-N tert-butyl N-[2-[4-(aminomethyl)phenoxy]ethyl]carbamate Chemical compound C(C)(C)(C)OC(NCCOC1=CC=C(C=C1)CN)=O DQBPFCICGMBSPQ-UHFFFAOYSA-N 0.000 description 1
- LNRYUDJQNIQFNO-UHFFFAOYSA-N tert-butyl N-[3-[4-(aminomethyl)phenyl]-1-(dimethylamino)-1-oxopropan-2-yl]carbamate Chemical compound NCC1=CC=C(C=C1)CC(C(=O)N(C)C)NC(OC(C)(C)C)=O LNRYUDJQNIQFNO-UHFFFAOYSA-N 0.000 description 1
- DTYUGOHKMHFOMT-UHFFFAOYSA-N tert-butyl n-[(4-bromo-2-fluorophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(Br)C=C1F DTYUGOHKMHFOMT-UHFFFAOYSA-N 0.000 description 1
- JDVJCRATZRUZNA-UHFFFAOYSA-N tert-butyl n-[(4-cyano-2-fluorophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(C#N)C=C1F JDVJCRATZRUZNA-UHFFFAOYSA-N 0.000 description 1
- XWYVCQSOGJIMPK-UHFFFAOYSA-N tert-butyl n-[(4-hydroxycyclohexyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCC(O)CC1 XWYVCQSOGJIMPK-UHFFFAOYSA-N 0.000 description 1
- APSWPAMGUUZLHS-UHFFFAOYSA-N tert-butyl n-[2-(4-iodoanilino)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCNC1=CC=C(I)C=C1 APSWPAMGUUZLHS-UHFFFAOYSA-N 0.000 description 1
- ZFCUPCJHJJNTRW-UHFFFAOYSA-N tert-butyl n-[3-[(4-cyanobenzoyl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC(=O)C1=CC=C(C#N)C=C1 ZFCUPCJHJJNTRW-UHFFFAOYSA-N 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- UURAUHCOJAIIRQ-QGLSALSOSA-N tiamulin Chemical compound CCN(CC)CCSCC(=O)O[C@@H]1C[C@@](C)(C=C)[C@@H](O)[C@H](C)[C@@]23CC[C@@H](C)[C@]1(C)[C@@H]2C(=O)CC3 UURAUHCOJAIIRQ-QGLSALSOSA-N 0.000 description 1
- 229960004885 tiamulin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LNPVWITZSLPXGG-UHFFFAOYSA-K trisodium 2-sulfonatoterephthalate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)c1ccc(C([O-])=O)c(c1)S([O-])(=O)=O LNPVWITZSLPXGG-UHFFFAOYSA-K 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- CRUISIDZTHMGJT-UHFFFAOYSA-L zinc;dichloride;hydrochloride Chemical compound Cl.[Cl-].[Cl-].[Zn+2] CRUISIDZTHMGJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/63—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4465—Non condensed piperidines, e.g. piperocaine only substituted in position 4
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/54—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—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
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/24—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one nitrogen and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/36—Sulfur atom
- C07D473/38—Sulfur atom attached in position 6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/76—Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members
- C07C2603/80—Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members containing eight-membered rings
- C07C2603/82—Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members containing eight-membered rings having three condensed rings with in total fourteen carbon atoms and having a having a [5.4.3.0(1,8)] ring structure, e.g. pleuromutiline
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14152107.0 | 2014-01-22 | ||
| EP14152107 | 2014-01-22 | ||
| PCT/EP2015/051159 WO2015110481A1 (en) | 2014-01-22 | 2015-01-21 | 12-epi-pleuromutilins |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017505304A JP2017505304A (ja) | 2017-02-16 |
| JP2017505304A5 JP2017505304A5 (enExample) | 2018-03-08 |
| JP6715772B2 true JP6715772B2 (ja) | 2020-07-01 |
Family
ID=49999754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016547848A Expired - Fee Related JP6715772B2 (ja) | 2014-01-22 | 2015-01-21 | 12−epi−プロイロムチリン |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9701628B2 (enExample) |
| EP (1) | EP3096751B1 (enExample) |
| JP (1) | JP6715772B2 (enExample) |
| KR (1) | KR102267807B1 (enExample) |
| CN (1) | CN105916499B (enExample) |
| BR (1) | BR112016015542B1 (enExample) |
| CA (1) | CA2935415C (enExample) |
| ES (1) | ES2861318T3 (enExample) |
| IL (1) | IL246454A0 (enExample) |
| MX (1) | MX368101B (enExample) |
| WO (1) | WO2015110481A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI762573B (zh) | 2017-02-10 | 2022-05-01 | 奧地利商納畢瓦治療有限責任公司 | 截短側耳素之純化 |
| CN107235971B (zh) * | 2017-07-31 | 2019-11-12 | 重庆华邦胜凯制药有限公司 | 一种制备瑞他莫林的新方法 |
| CN109666009B (zh) * | 2018-11-02 | 2023-02-03 | 华南农业大学 | 一种以2-氨基苯巯醇为连接基团截短侧耳素衍生物制备方法和用途 |
| WO2020210158A1 (en) * | 2019-04-06 | 2020-10-15 | The Board Of Trustees Of The University Of Illinois | Compounds that induce ferroptic cell death |
| JP7260665B2 (ja) * | 2019-04-20 | 2023-04-18 | エルジー エレクトロニクス インコーポレイティド | Bdpcmに基づく映像コーディング方法、及びその装置 |
| EP4135683B9 (en) * | 2020-04-17 | 2025-12-10 | ARIVA Med GmbH | Antiviral use of pleuromutilins |
| WO2021219399A1 (en) | 2020-04-28 | 2021-11-04 | Nabriva Therapeutics GmbH | Novel 12-epi-mutilin compounds, process for preparing the same and uses thereof |
| US11351149B2 (en) | 2020-09-03 | 2022-06-07 | Pfizer Inc. | Nitrile-containing antiviral compounds |
| US11117859B1 (en) * | 2021-02-12 | 2021-09-14 | Shaanxi University Of Science And Technology | Pleuromutilin hippuric acid ester with antibacterial activity and a method of preparing the same |
| TW202309043A (zh) | 2021-04-16 | 2023-03-01 | 奧地利商納畢瓦治療有限責任公司 | 新穎12—表—木替靈(12—epi—mutilin)化合物及其用途 |
| CN116199690B (zh) * | 2023-04-28 | 2023-07-07 | 西华大学 | 嘌呤类截短侧耳素衍生物、立体异构体或药学上可接受的盐及其用途和药物组合物 |
| WO2025081213A1 (en) | 2023-10-21 | 2025-04-24 | Ariva Med Gmbh | NOVEL USES OF 12-EPI-MUTILIN COMPOUNDs |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003523729A (ja) | 1999-05-20 | 2003-08-12 | スミスクライン・ビーチャム・コーポレイション | 原核生物リボソームの活性を変調する方法 |
| WO2006070671A1 (ja) | 2004-12-27 | 2006-07-06 | Kyorin Pharmaceutical Co., Ltd. | 12位置換ムチリン誘導体 |
| JP2006306727A (ja) * | 2005-04-26 | 2006-11-09 | Kyorin Pharmaceut Co Ltd | ピリジン環を14位置換基に有する12位置換ムチリン誘導体 |
| EP1896404B1 (en) * | 2005-06-27 | 2014-09-17 | Nabriva Therapeutics AG | Pleuromutilin derivatives containing a hydroxyamino- or acyloxyaminocycloalkyl group |
| GB0513058D0 (en) * | 2005-06-27 | 2005-08-03 | Sandoz Ag | Organic compounds |
| EP1808431A1 (en) * | 2006-01-16 | 2007-07-18 | Nabriva Therapeutics Forschungs GmbH | Mutilin derivatives and their use as pharmaceutical |
| WO2008117796A1 (ja) | 2007-03-28 | 2008-10-02 | Dainippon Sumitomo Pharma Co., Ltd. | 新規ムチリン誘導体 |
| JP2008280297A (ja) * | 2007-05-11 | 2008-11-20 | Kyorin Pharmaceut Co Ltd | 12位ヘテロ置換ムチリン誘導体 |
| WO2008143343A1 (ja) | 2007-05-24 | 2008-11-27 | Kyorin Pharmaceutical Co., Ltd. | 14位置換基に複素芳香環カルボン酸構造を有するムチリン誘導体 |
| EP2014640A1 (en) * | 2007-07-13 | 2009-01-14 | Nabriva Therapeutics AG | Pleuromutilin derivatives |
| JP2009040709A (ja) * | 2007-08-08 | 2009-02-26 | Kyorin Pharmaceut Co Ltd | 12位置換ムチリン誘導体 |
| EP2159220A1 (en) | 2008-09-02 | 2010-03-03 | Nabriva Therapeutics AG | Organic compounds |
| JP2010100582A (ja) | 2008-10-24 | 2010-05-06 | Kyorin Pharmaceut Co Ltd | 14位置換基に複素芳香環カルボン酸構造を有するムチリン誘導体 |
-
2015
- 2015-01-21 EP EP15701513.2A patent/EP3096751B1/en active Active
- 2015-01-21 ES ES15701513T patent/ES2861318T3/es active Active
- 2015-01-21 US US15/111,390 patent/US9701628B2/en active Active
- 2015-01-21 BR BR112016015542-4A patent/BR112016015542B1/pt not_active IP Right Cessation
- 2015-01-21 WO PCT/EP2015/051159 patent/WO2015110481A1/en not_active Ceased
- 2015-01-21 CN CN201580005582.5A patent/CN105916499B/zh active Active
- 2015-01-21 JP JP2016547848A patent/JP6715772B2/ja not_active Expired - Fee Related
- 2015-01-21 KR KR1020167022050A patent/KR102267807B1/ko not_active Expired - Fee Related
- 2015-01-21 MX MX2016008781A patent/MX368101B/es active IP Right Grant
- 2015-01-21 CA CA2935415A patent/CA2935415C/en active Active
-
2016
- 2016-06-26 IL IL246454A patent/IL246454A0/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP3096751B1 (en) | 2021-01-06 |
| CN105916499B (zh) | 2020-02-18 |
| IL246454A0 (en) | 2016-08-31 |
| JP2017505304A (ja) | 2017-02-16 |
| MX2016008781A (es) | 2017-03-23 |
| US20160332963A1 (en) | 2016-11-17 |
| US9701628B2 (en) | 2017-07-11 |
| EP3096751A1 (en) | 2016-11-30 |
| BR112016015542B1 (pt) | 2022-08-30 |
| WO2015110481A1 (en) | 2015-07-30 |
| CN105916499A (zh) | 2016-08-31 |
| MX368101B (es) | 2019-09-19 |
| WO2015110481A8 (en) | 2016-03-03 |
| CA2935415A1 (en) | 2015-07-30 |
| CA2935415C (en) | 2023-05-16 |
| KR20160111417A (ko) | 2016-09-26 |
| ES2861318T3 (es) | 2021-10-06 |
| BR112016015542A8 (pt) | 2020-06-02 |
| KR102267807B1 (ko) | 2021-06-22 |
| BR112016015542A2 (enExample) | 2017-08-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6715772B2 (ja) | 12−epi−プロイロムチリン | |
| TWI574941B (zh) | 抗菌劑 | |
| AU777472B2 (en) | Compounds and pharmaceutical compositions as cathepsin S inhibitors | |
| US20070167495A1 (en) | Pleuromutilin derivatives, process for their preparation and uses thereof | |
| JP2004502752A (ja) | 9−置換ミノサイクリン化合物 | |
| TW201000433A (en) | Salts and polymorphs of a tetracycline compound | |
| JPH08512046A (ja) | 抗アテローム性動脈硬化症ジアリール化合物 | |
| MX2013005200A (es) | Derivados de acido hidroxamico y su so en el tratamiento de infecciones bacterianas. | |
| CN102459153A (zh) | 四环素类化合物 | |
| JP5628173B2 (ja) | 有機化合物 | |
| EA019579B1 (ru) | Производные мутилина и их применение в качестве фармацевтических препаратов | |
| JP4209672B2 (ja) | 新規化合物 | |
| CN117500809A (zh) | 新的12-差向异构-莫林化合物及其用途 | |
| US9278920B2 (en) | Pleuromutilin derivatives for use in the treatment of diseases mediated by microbes | |
| US20010044547A1 (en) | Antiviral protease inhibitors | |
| HK1226653B (en) | 12-epi-pleuromutilins | |
| AU2002301207B2 (en) | Antiviral protease inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20170615 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180117 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180117 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180927 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181002 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20181225 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190401 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190820 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20191114 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200114 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200220 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200511 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200609 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6715772 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |