DK2742045T3 - ANTIBACTERIAL CYCLOPENTA [C] PYRROL-SUBSTITUTED 3,4-DIHYDRO-1H- [1,8] NAPHTHYRIDINONES - Google Patents

ANTIBACTERIAL CYCLOPENTA [C] PYRROL-SUBSTITUTED 3,4-DIHYDRO-1H- [1,8] NAPHTHYRIDINONES Download PDF

Info

Publication number: DK2742045T3
Authority: DK; Denmark
Prior art keywords: mmol; formula; hydrogen; alkyl; compounds
Prior art date: 2011-08-10

Application number

DK12746093.9T

Other languages

Danish (da)

English (en)

Inventor

Jerôme Emile Georges Guillemont

David Francis Alain Lançois

Magali Madeleine Simone Motte

Anil Koul

Wendy Mia Albert Balemans

Eric Pierre Alexandre Arnoult

Original Assignee

Janssen Sciences Ireland Unlimited Co

Priority date (The priority date 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 date listed.)

2011-08-10

Filing date

2012-08-10

Publication date

2019-04-23

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=46650549&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK2742045(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2012-08-10 Application filed by Janssen Sciences Ireland Unlimited Co filed Critical Janssen Sciences Ireland Unlimited Co

2019-04-23 Application granted granted Critical

2019-04-23 Publication of DK2742045T3 publication Critical patent/DK2742045T3/en

Links

230000000844 anti-bacterial effect Effects 0.000 title description 10
150000001875 compounds Chemical class 0.000 claims description 162
238000000034 method Methods 0.000 claims description 43
238000006243 chemical reaction Methods 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 36
-1 3-dihydro-1H-indolyl Chemical group 0.000 claims description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
125000001072 heteroaryl group Chemical group 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 25
102000004190 Enzymes Human genes 0.000 claims description 22
108090000790 Enzymes Proteins 0.000 claims description 22
125000001424 substituent group Chemical group 0.000 claims description 19
229910052757 nitrogen Chemical group 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 16
208000035143 Bacterial infection Diseases 0.000 claims description 15
208000022362 bacterial infectious disease Diseases 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 15
241000894006 Bacteria Species 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 10
125000004104 aryloxy group Chemical group 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
125000003226 pyrazolyl group Chemical group 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000003831 tetrazolyl group Chemical group 0.000 claims description 6
125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
125000001425 triazolyl group Chemical group 0.000 claims description 6
125000000168 pyrrolyl group Chemical group 0.000 claims description 4
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 2
125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims 18
229910052736 halogen Inorganic materials 0.000 claims 10
150000002367 halogens Chemical class 0.000 claims 10
125000003545 alkoxy group Chemical group 0.000 claims 4
150000002431 hydrogen Chemical class 0.000 claims 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
101100174574 Mus musculus Pikfyve gene Proteins 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
125000005605 benzo group Chemical group 0.000 claims 1
239000000543 intermediate Substances 0.000 description 153
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 149
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 124
239000000203 mixture Substances 0.000 description 95
239000000243 solution Substances 0.000 description 76
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
229910001868 water Inorganic materials 0.000 description 67
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
235000019439 ethyl acetate Nutrition 0.000 description 58
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
239000000741 silica gel Substances 0.000 description 44
229910002027 silica gel Inorganic materials 0.000 description 44
229960001866 silicon dioxide Drugs 0.000 description 44
239000012044 organic layer Substances 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
239000011541 reaction mixture Substances 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
229910052943 magnesium sulfate Inorganic materials 0.000 description 32
235000019341 magnesium sulphate Nutrition 0.000 description 32
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
239000012071 phase Substances 0.000 description 27
125000005843 halogen group Chemical group 0.000 description 23
229910000027 potassium carbonate Inorganic materials 0.000 description 23
239000003480 eluent Substances 0.000 description 21
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
239000012267 brine Substances 0.000 description 20
239000003208 petroleum Substances 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
239000002904 solvent Substances 0.000 description 20
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
235000015320 potassium carbonate Nutrition 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
238000003818 flash chromatography Methods 0.000 description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
239000012300 argon atmosphere Substances 0.000 description 14
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
239000007787 solid Substances 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
230000001580 bacterial effect Effects 0.000 description 13
239000000725 suspension Substances 0.000 description 13
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 12
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 12
239000000047 product Substances 0.000 description 12
238000002347 injection Methods 0.000 description 11
239000007924 injection Substances 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
230000000694 effects Effects 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
239000007832 Na2SO4 Substances 0.000 description 9
235000011114 ammonium hydroxide Nutrition 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
208000015181 infectious disease Diseases 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
238000012360 testing method Methods 0.000 description 9
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
239000000796 flavoring agent Substances 0.000 description 8
235000019634 flavors Nutrition 0.000 description 8
238000009472 formulation Methods 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
239000003999 initiator Substances 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
239000003643 water by type Substances 0.000 description 8
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
241000699670 Mus sp. Species 0.000 description 7
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
238000003556 assay Methods 0.000 description 7
230000008901 benefit Effects 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
125000004356 hydroxy functional group Chemical group O* 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
239000007788 liquid Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 6
108010039731 Fatty Acid Synthases Proteins 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
235000019441 ethanol Nutrition 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000000843 powder Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
241000191967 Staphylococcus aureus Species 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
235000003599 food sweetener Nutrition 0.000 description 5
238000001819 mass spectrum Methods 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000003765 sweetening agent Substances 0.000 description 5
238000004704 ultra performance liquid chromatography Methods 0.000 description 5
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
239000005695 Ammonium acetate Substances 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
238000002835 absorbance Methods 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
235000019257 ammonium acetate Nutrition 0.000 description 4
229940043376 ammonium acetate Drugs 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
150000004665 fatty acids Chemical class 0.000 description 4
125000001153 fluoro group Chemical group F* 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000002054 inoculum Substances 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000002609 medium Substances 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
235000011056 potassium acetate Nutrition 0.000 description 4
238000004262 preparative liquid chromatography Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
101710146995 Acyl carrier protein Proteins 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
239000000654 additive Substances 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
230000037396 body weight Effects 0.000 description 3
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 3
230000008859 change Effects 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
231100000135 cytotoxicity Toxicity 0.000 description 3
230000003013 cytotoxicity Effects 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000000132 electrospray ionisation Methods 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
238000005259 measurement Methods 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
239000006199 nebulizer Substances 0.000 description 3
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 3
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 3
RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 2
DCNMATSPQKWETQ-UHFFFAOYSA-N (5-acetylthiophen-2-yl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)S1 DCNMATSPQKWETQ-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
QZTKDVCDBIDYMD-UHFFFAOYSA-N 2,2'-[(2-amino-2-oxoethyl)imino]diacetic acid Chemical compound NC(=O)CN(CC(O)=O)CC(O)=O QZTKDVCDBIDYMD-UHFFFAOYSA-N 0.000 description 2
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 2
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
VJEOGGNIBLORIJ-UHFFFAOYSA-N 6-bromo-3,4-dihydro-1h-1,8-naphthyridin-2-one Chemical compound N1C(=O)CCC2=CC(Br)=CN=C21 VJEOGGNIBLORIJ-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
102000014914 Carrier Proteins Human genes 0.000 description 2
108010078791 Carrier Proteins Proteins 0.000 description 2
102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
241000606768 Haemophilus influenzae Species 0.000 description 2
101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 2
RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
108090000854 Oxidoreductases Proteins 0.000 description 2
102000004316 Oxidoreductases Human genes 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 2
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000006696 biosynthetic metabolic pathway Effects 0.000 description 2
IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
238000002815 broth microdilution Methods 0.000 description 2
239000007853 buffer solution Substances 0.000 description 2
235000013736 caramel Nutrition 0.000 description 2
230000003833 cell viability Effects 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
XWRLQRLQUKZEEU-UHFFFAOYSA-N ethyl(hydroxy)silicon Chemical class CC[Si]O XWRLQRLQUKZEEU-UHFFFAOYSA-N 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
229960003085 meticillin Drugs 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
235000013615 non-nutritive sweetener Nutrition 0.000 description 2
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000010970 precious metal Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000012453 solvate Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
235000019408 sucralose Nutrition 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
JJOBBHMBMRQQHU-UHFFFAOYSA-N tert-butyl n-prop-2-enyl-n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)N(CC=C)CC#C JJOBBHMBMRQQHU-UHFFFAOYSA-N 0.000 description 2
150000003536 tetrazoles Chemical class 0.000 description 2
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 2
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 2
239000000080 wetting agent Substances 0.000 description 2
UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
QTGPYSQUEPGBHV-UHFFFAOYSA-N (2-acetylthiophen-3-yl)boronic acid Chemical compound CC(=O)C=1SC=CC=1B(O)O QTGPYSQUEPGBHV-UHFFFAOYSA-N 0.000 description 1
VRDAOVQZVXYRNH-UHFFFAOYSA-N (2-chloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=CN=C1Cl VRDAOVQZVXYRNH-UHFFFAOYSA-N 0.000 description 1
JWVLMZZYJOJCTI-UHFFFAOYSA-N (2-chlorothiophen-3-yl)boronic acid Chemical compound OB(O)C=1C=CSC=1Cl JWVLMZZYJOJCTI-UHFFFAOYSA-N 0.000 description 1
NPLZNDDFVCGRAG-UHFFFAOYSA-N (2-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C#N NPLZNDDFVCGRAG-UHFFFAOYSA-N 0.000 description 1
QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 1
ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 1
NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
NUFKRGBSZPCGQB-FLBSXDLDSA-N (3s)-3-amino-4-oxo-4-[[(2r)-1-oxo-1-[(2,2,4,4-tetramethylthietan-3-yl)amino]propan-2-yl]amino]butanoic acid;pentahydrate Chemical compound O.O.O.O.O.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C NUFKRGBSZPCGQB-FLBSXDLDSA-N 0.000 description 1
YUTPAZKVEOJQCY-UHFFFAOYSA-N (4-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=NC=C1B(O)O YUTPAZKVEOJQCY-UHFFFAOYSA-N 0.000 description 1
DFUMIZDUIJNUJU-UHFFFAOYSA-N (4-methylthiophen-2-yl)boronic acid Chemical compound CC1=CSC(B(O)O)=C1 DFUMIZDUIJNUJU-UHFFFAOYSA-N 0.000 description 1
LVPFZXKLROORIK-UHFFFAOYSA-N (4-methylthiophen-3-yl)boronic acid Chemical compound CC1=CSC=C1B(O)O LVPFZXKLROORIK-UHFFFAOYSA-N 0.000 description 1
JFCLNCVCDFUJPO-UHFFFAOYSA-N (5-chlorothiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)S1 JFCLNCVCDFUJPO-UHFFFAOYSA-N 0.000 description 1
ZEOMEPSYIIQIND-UHFFFAOYSA-N (5-cyanothiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)S1 ZEOMEPSYIIQIND-UHFFFAOYSA-N 0.000 description 1
LMJIDBVSSSPRII-UHFFFAOYSA-N (5-methylfuran-2-yl)boronic acid Chemical compound CC1=CC=C(B(O)O)O1 LMJIDBVSSSPRII-UHFFFAOYSA-N 0.000 description 1
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 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
DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
DXLQEJHUQKKSRB-UHFFFAOYSA-N 1,1,1-trifluoro-n-pyridin-2-yl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=N1 DXLQEJHUQKKSRB-UHFFFAOYSA-N 0.000 description 1
125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 1
HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 1
QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 1
JRGGUPZKKTVKOV-UHFFFAOYSA-N 1-bromo-3-chlorobenzene Chemical compound ClC1=CC=CC(Br)=C1 JRGGUPZKKTVKOV-UHFFFAOYSA-N 0.000 description 1
NHDODQWIKUYWMW-UHFFFAOYSA-N 1-bromo-4-chlorobenzene Chemical compound ClC1=CC=C(Br)C=C1 NHDODQWIKUYWMW-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
UCNGGGYMLHAMJG-UHFFFAOYSA-N 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(C)C=C1B1OC(C)(C)C(C)(C)O1 UCNGGGYMLHAMJG-UHFFFAOYSA-N 0.000 description 1
HLXOVAMYQUFLPE-UHFFFAOYSA-N 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound CN1N=CC=C1B1OC(C)(C)C(C)(C)O1 HLXOVAMYQUFLPE-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
CCBICDLNWJRFPO-UHFFFAOYSA-N 2,6-dichloroindophenol Chemical compound C1=CC(O)=CC=C1N=C1C=C(Cl)C(=O)C(Cl)=C1 CCBICDLNWJRFPO-UHFFFAOYSA-N 0.000 description 1
FXKKXDGOIQJEJS-UHFFFAOYSA-N 2-(3-methoxythiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C1=CSC(B2OC(C)(C)C(C)(C)O2)=C1OC FXKKXDGOIQJEJS-UHFFFAOYSA-N 0.000 description 1
RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
NSMKWTGDPQHTDH-UHFFFAOYSA-N 2-bromo-5-methyl-1,3,4-thiadiazole Chemical compound CC1=NN=C(Br)S1 NSMKWTGDPQHTDH-UHFFFAOYSA-N 0.000 description 1
TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
DGJCULPYCMEHFZ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-(3-methylthiophen-2-yl)-1,3,2-dioxaborolane Chemical compound C1=CSC(B2OC(C)(C)C(C)(C)O2)=C1C DGJCULPYCMEHFZ-UHFFFAOYSA-N 0.000 description 1
LTOLNTYOBPPFLS-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-(5-methylthiophen-2-yl)-1,3,2-dioxaborolane Chemical compound S1C(C)=CC=C1B1OC(C)(C)C(C)(C)O1 LTOLNTYOBPPFLS-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
WSRGGSAGSUEJKQ-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=CN=C1 WSRGGSAGSUEJKQ-UHFFFAOYSA-N 0.000 description 1
WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
108700037654 Acyl carrier protein (ACP) Proteins 0.000 description 1
102000048456 Acyl carrier protein (ACP) Human genes 0.000 description 1
208000010470 Ageusia Diseases 0.000 description 1
239000004377 Alitame Substances 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
206010053555 Arthritis bacterial Diseases 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
241000193738 Bacillus anthracis Species 0.000 description 1
206010066798 Bacterial tracheitis Diseases 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
208000004020 Brain Abscess Diseases 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
206010007882 Cellulitis Diseases 0.000 description 1
206010007918 Cellulitis orbital Diseases 0.000 description 1
241000873310 Citrobacter sp. Species 0.000 description 1
206010010741 Conjunctivitis Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
102100034289 Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 Human genes 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
206010014568 Empyema Diseases 0.000 description 1
241000792859 Enema Species 0.000 description 1
108010060861 Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) Proteins 0.000 description 1
206010016936 Folliculitis Diseases 0.000 description 1
235000016623 Fragaria vesca Nutrition 0.000 description 1
240000009088 Fragaria x ananassa Species 0.000 description 1
235000011363 Fragaria x ananassa Nutrition 0.000 description 1
241000589602 Francisella tularensis Species 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
238000007341 Heck reaction Methods 0.000 description 1
101000641031 Homo sapiens Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010021531 Impetigo Diseases 0.000 description 1
208000004575 Infectious Arthritis Diseases 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
241000186779 Listeria monocytogenes Species 0.000 description 1
231100000002 MTT assay Toxicity 0.000 description 1
238000000134 MTT assay Methods 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
108050004114 Monellin Proteins 0.000 description 1
241000588655 Moraxella catarrhalis Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000187479 Mycobacterium tuberculosis Species 0.000 description 1
241000588650 Neisseria meningitidis Species 0.000 description 1
208000000493 Orbital Cellulitis Diseases 0.000 description 1
206010031252 Osteomyelitis Diseases 0.000 description 1
206010033078 Otitis media Diseases 0.000 description 1
229910020667 PBr3 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
206010034531 Perinephric abscess Diseases 0.000 description 1
206010057182 Periorbital cellulitis Diseases 0.000 description 1
240000006711 Pistacia vera Species 0.000 description 1
241000588770 Proteus mirabilis Species 0.000 description 1
241000588767 Proteus vulgaris Species 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
206010038975 Retroperitoneal abscess Diseases 0.000 description 1
240000001890 Ribes hudsonianum Species 0.000 description 1
235000016954 Ribes hudsonianum Nutrition 0.000 description 1
235000001466 Ribes nigrum Nutrition 0.000 description 1
235000011034 Rubus glaucus Nutrition 0.000 description 1
244000235659 Rubus idaeus Species 0.000 description 1
235000009122 Rubus idaeus Nutrition 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
241000607149 Salmonella sp. Species 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
241000607714 Serratia sp. Species 0.000 description 1
241000607758 Shigella sp. Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
241000191963 Staphylococcus epidermidis Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
241000122973 Stenotrophomonas maltophilia Species 0.000 description 1
UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
239000004376 Sucralose Substances 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
MNOILHPDHOHILI-UHFFFAOYSA-N Tetramethylthiourea Chemical compound CN(C)C(=S)N(C)C MNOILHPDHOHILI-UHFFFAOYSA-N 0.000 description 1
244000299461 Theobroma cacao Species 0.000 description 1
206010044248 Toxic shock syndrome Diseases 0.000 description 1
231100000650 Toxic shock syndrome Toxicity 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
206010052428 Wound Diseases 0.000 description 1
206010048038 Wound infection Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
206010000269 abscess Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
235000010358 acesulfame potassium Nutrition 0.000 description 1
229960004998 acesulfame potassium Drugs 0.000 description 1
239000000619 acesulfame-K Substances 0.000 description 1
208000013086 acute epiglottitis Diseases 0.000 description 1
241001148470 aerobic bacillus Species 0.000 description 1
235000019666 ageusia Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
235000019409 alitame Nutrition 0.000 description 1
108010009985 alitame Proteins 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
238000009635 antibiotic susceptibility testing Methods 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
229940065181 bacillus anthracis Drugs 0.000 description 1
208000029212 bacterial myositis Diseases 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
239000012964 benzotriazole Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000001851 biosynthetic effect Effects 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
208000010217 blepharitis Diseases 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
QARVLSVVCXYDNA-IDEBNGHGSA-N bromobenzene Chemical group Br[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 QARVLSVVCXYDNA-IDEBNGHGSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
GSHUZVSNIBLGMR-UHFFFAOYSA-N calcium;1,1-dioxo-1,2-benzothiazol-3-one Chemical compound [Ca].C1=CC=C2C(=O)NS(=O)(=O)C2=C1 GSHUZVSNIBLGMR-UHFFFAOYSA-N 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
235000019219 chocolate Nutrition 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000001332 colony forming effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
KFWWCMJSYSSPSK-PAXLJYGASA-N crotonoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)/C=C/C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 KFWWCMJSYSSPSK-PAXLJYGASA-N 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000009109 curative therapy Methods 0.000 description 1
239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
230000006378 damage Effects 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
230000001934 delay Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
206010014665 endocarditis Diseases 0.000 description 1
206010014801 endophthalmitis Diseases 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
201000010063 epididymitis Diseases 0.000 description 1
208000001606 epiglottitis Diseases 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000005284 excitation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000013020 final formulation Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
229940118764 francisella tularensis Drugs 0.000 description 1
239000008369 fruit flavor Substances 0.000 description 1
PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
238000003304 gavage Methods 0.000 description 1
239000007897 gelcap Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002303 glucose derivatives Chemical class 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000009036 growth inhibition Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
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 description 1
235000012907 honey Nutrition 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
201000007119 infective endocarditis Diseases 0.000 description 1
208000014674 injury Diseases 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000000905 isomalt Substances 0.000 description 1
235000010439 isomalt Nutrition 0.000 description 1
HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
206010023332 keratitis Diseases 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
239000003446 ligand Substances 0.000 description 1
229960003907 linezolid Drugs 0.000 description 1
TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
229940115931 listeria monocytogenes Drugs 0.000 description 1
HTQGBLGOGSATJZ-UHFFFAOYSA-J lithium lanthanum(3+) tetrachloride Chemical compound [Li+].[Cl-].[Cl-].[Cl-].[Cl-].[La+3] HTQGBLGOGSATJZ-UHFFFAOYSA-J 0.000 description 1
238000011068 loading method Methods 0.000 description 1
201000003453 lung abscess Diseases 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
229940087646 methanolamine Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
FEKRFYZGYUTGRY-UHFFFAOYSA-N n'-ethylmethanediimine Chemical compound CCN=C=N FEKRFYZGYUTGRY-UHFFFAOYSA-N 0.000 description 1
VHSIAYLBCLUAFT-UHFFFAOYSA-N n-[3-acetyl-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1-methyl-2-oxo-1,8-naphthyridin-4-yl]acetamide Chemical class C=1C=C(Cl)C=CC=1C=1C=C2C(NC(=O)C)=C(C(C)=O)C(=O)N(C)C2=NC=1C1=CC=C(Cl)C=C1Cl VHSIAYLBCLUAFT-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
SUWZHLCNFQWNPE-LATRNWQMSA-N optochin Chemical compound C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 SUWZHLCNFQWNPE-LATRNWQMSA-N 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
244000052769 pathogen Species 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
206010034674 peritonitis Diseases 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
229940007042 proteus vulgaris Drugs 0.000 description 1
QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
230000004044 response Effects 0.000 description 1
150000004671 saturated fatty acids Chemical class 0.000 description 1
235000003441 saturated fatty acids Nutrition 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
201000001223 septic arthritis Diseases 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 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
229960001462 sodium cyclamate Drugs 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
241000894007 species Species 0.000 description 1
201000005789 splenic abscess Diseases 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
229940013618 stevioside Drugs 0.000 description 1
OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
235000019202 steviosides Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
229960005137 succinic acid Drugs 0.000 description 1
BAQAVOSOZGMPRM-UHFFFAOYSA-N sucralose Chemical compound OC1C(O)C(Cl)C(CO)OC1OC1(CCl)C(O)C(O)C(CCl)O1 BAQAVOSOZGMPRM-UHFFFAOYSA-N 0.000 description 1
BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
IPISOFJLWYBCAV-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound C1=NN(C(=O)OC(C)(C)C)C=C1B1OC(C)(C)C(C)(C)O1 IPISOFJLWYBCAV-UHFFFAOYSA-N 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
XGTPDIIFEPTULX-UHFFFAOYSA-N tert-butyl prop-2-ynoate Chemical compound CC(C)(C)OC(=O)C#C XGTPDIIFEPTULX-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
YPPSVJYUVRPSMX-UHFFFAOYSA-N thiophen-2-ylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CS1 YPPSVJYUVRPSMX-UHFFFAOYSA-N 0.000 description 1
QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
206010043778 thyroiditis Diseases 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
CNQDVAWRPXCHEG-UHFFFAOYSA-K trilithium;trichloride Chemical compound [Li+].[Li+].[Li+].[Cl-].[Cl-].[Cl-] CNQDVAWRPXCHEG-UHFFFAOYSA-K 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
239000006150 trypticase soy agar Substances 0.000 description 1
229910021642 ultra pure water Inorganic materials 0.000 description 1
239000012498 ultrapure water Substances 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
WRSWIWOVJBYZAW-UHFFFAOYSA-M zinc;methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=CC=C1 WRSWIWOVJBYZAW-UHFFFAOYSA-M 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

DK12746093.9T 2011-08-10 2012-08-10 ANTIBACTERIAL CYCLOPENTA [C] PYRROL-SUBSTITUTED 3,4-DIHYDRO-1H- [1,8] NAPHTHYRIDINONES DK2742045T3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP11177119		2011-08-10
PCT/EP2012/065733 WO2013021054A1 (en)	2011-08-10	2012-08-10	Antibacterial cyclopenta[c]pyrrole substituted 3,4-dihydro-1h-[1,8]naphthyridinones

Publications (1)

Publication Number	Publication Date
DK2742045T3 true DK2742045T3 (en)	2019-04-23

Family

ID=46650549

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK12746093.9T DK2742045T3 (en)	2011-08-10	2012-08-10	ANTIBACTERIAL CYCLOPENTA [C] PYRROL-SUBSTITUTED 3,4-DIHYDRO-1H- [1,8] NAPHTHYRIDINONES

Country Status (24)

Country	Link
US (7)	US8906923B2 (2)
EP (1)	EP2742045B1 (2)
JP (2)	JP5921687B2 (2)
KR (1)	KR101996862B1 (2)
CN (2)	CN103874698B (2)
AR (1)	AR087508A1 (2)
AU (1)	AU2012293621B2 (2)
BR (1)	BR112014003063B1 (2)
CA (1)	CA2842518C (2)
CL (1)	CL2014000289A1 (2)
DK (1)	DK2742045T3 (2)
EA (1)	EA201490438A1 (2)
ES (1)	ES2721658T3 (2)
HU (1)	HUE042978T2 (2)
IL (1)	IL230549A (2)
JO (1)	JO3611B1 (2)
MX (1)	MX348128B (2)
PE (1)	PE20141410A1 (2)
PH (1)	PH12014500317A1 (2)
TR (1)	TR201905537T4 (2)
TW (1)	TWI568731B (2)
UA (1)	UA111210C2 (2)
UY (1)	UY34253A (2)
WO (1)	WO2013021054A1 (2)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JO3611B1 (ar) *	2011-08-10	2020-08-27	Janssen Sciences Ireland Uc	سايكلو بنتا (سي (بيرول 4,3 ثاني هيدرو 1 hمستبدله [8,1] نافثيريدينونات مضادة للجراثيم
EP2742047B1 (en)	2011-08-10	2021-05-12	Janssen Sciences Ireland Unlimited Company	Antibacterial piperidinyl substituted 3,4-dihydro-1h-[1,8]naphthyridinones
CN104981466B (zh) *	2012-08-10	2019-06-14	爱尔兰詹森科学公司	抗细菌化合物
WO2015048507A1 (en)	2013-09-26	2015-04-02	Mnemosyne Pharmaceuticals, Inc.	Selective octahydro-cyclopenta[c] pyrrole negative modulators of nr2b
JO3579B1 (ar) *	2014-09-26	2020-07-05	Luc Therapeutics Inc	مُعدِلات تفاغرية سالبة لمستقبل nr2b من المركب n-ألكيل أريل-5-أوكسي أريل-ثامن هيدرو-خماسي الحلقة [c] بيرول
ES2747768T3 (es)	2017-03-20	2020-03-11	Forma Therapeutics Inc	Composiciones de pirrolopirrol como activadores de quinasa de piruvato (PKR)
WO2019177975A1 (en)	2018-03-12	2019-09-19	The Board Of Trustees Of The University Of Illinois	Antibiotics effective for gram-negative pathogens
US12053458B2 (en)	2018-09-19	2024-08-06	Novo Nordisk Health Care Ag	Treating sickle cell disease with a pyruvate kinase R activating compound
ES2989438T3 (es)	2018-09-19	2024-11-26	Novo Nordisk Healthcare Ag	Activación de la piruvato cinasa R
CA3119390A1 (en)	2018-11-12	2020-05-22	Debiopharm International S.A.	Antibiotic compounds, methods of manufacturing the same, pharmaceutical compositions containing the same and uses thereof
US20220378756A1 (en)	2019-09-19	2022-12-01	Forma Therapeutics, Inc.	Activating pyruvate kinase r
MX2023010941A (es) *	2021-03-17	2023-11-28	Janssen Sciences Ireland Unlimited Co	Compuestos antibacterianos.
US12128035B2 (en)	2021-03-19	2024-10-29	Novo Nordisk Health Care Ag	Activating pyruvate kinase R

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4215123A (en) *	1979-05-07	1980-07-29	American Home Products Corporation	Antisecretory 4-oxy-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives
ATE285821T1 (de)	1999-10-08	2005-01-15	Affinium Pharm Inc	Fab i inhibitoren
CO5251397A1 (es)	1999-10-08	2003-02-28	Smithkline Beecham Corp	Inhibidores de fab i
ATE294578T1 (de)	1999-10-08	2005-05-15	Affinium Pharm Inc	Fab i hemmer
CA2444597A1 (en)	2001-04-06	2002-10-06	Affinium Pharmaceuticals, Inc.	Fab i inhibitors
EP2848614A3 (en) *	2004-06-04	2015-07-29	Debiopharm International SA	Acrylamide derivatives as antibiotic agents
US7732612B2 (en)	2004-09-09	2010-06-08	Janssen Pharmaceutica, N.V.	7-amino alkylidenyl-heterocyclic quinolones and naphthyridones
US7973060B2 (en)	2005-10-13	2011-07-05	Crystalgenomics, Inc.	Fab I inhibitor and process for preparing same
EP2687533B1 (en) *	2006-07-20	2017-07-19	Debiopharm International SA	Acrylamide derivatives as FAB I inhibitors
WO2008098374A1 (en)	2007-02-16	2008-08-21	Affinium Pharmaceuticals, Inc.	Salts, prodrugs and polymorphs of fab i inhibitors
MX2012005759A (es) *	2009-11-18	2012-10-03	Fab Pharma S A S	Acrilamidas heterociclicas novedosas y su uso como farmacos.
JP2014524409A (ja)	2011-07-29	2014-09-22	ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィア	Ｈｉｖの治療のための組成物および方法
US8766017B2 (en)	2011-07-29	2014-07-01	Eastman Chemical Company	Integrated process for the preparation of 1,4-cyclohexanedimethanol from terephthalic acid
US9394295B2 (en)	2011-08-10	2016-07-19	Janssen Sciences Ireland Uc	Antibacterial homopiperidinyl substituted 3,4-dihydro-1H-[1,8]naphthyridinones
EP2742047B1 (en)	2011-08-10	2021-05-12	Janssen Sciences Ireland Unlimited Company	Antibacterial piperidinyl substituted 3,4-dihydro-1h-[1,8]naphthyridinones
JO3611B1 (ar) *	2011-08-10	2020-08-27	Janssen Sciences Ireland Uc	سايكلو بنتا (سي (بيرول 4,3 ثاني هيدرو 1 hمستبدله [8,1] نافثيريدينونات مضادة للجراثيم

2012
- 2012-08-07 JO JOP/2012/0223A patent/JO3611B1/ar active
- 2012-08-10 AR ARP120102929A patent/AR087508A1/es active IP Right Grant
- 2012-08-10 JP JP2014524410A patent/JP5921687B2/ja not_active Expired - Fee Related
- 2012-08-10 AU AU2012293621A patent/AU2012293621B2/en not_active Ceased
- 2012-08-10 MX MX2014001600A patent/MX348128B/es active IP Right Grant
- 2012-08-10 EA EA201490438A patent/EA201490438A1/ru unknown
- 2012-08-10 CA CA2842518A patent/CA2842518C/en active Active
- 2012-08-10 BR BR112014003063-4A patent/BR112014003063B1/pt active IP Right Grant
- 2012-08-10 UY UY0001034253A patent/UY34253A/es active IP Right Grant
- 2012-08-10 PH PH1/2014/500317A patent/PH12014500317A1/en unknown
- 2012-08-10 KR KR1020147005329A patent/KR101996862B1/ko not_active Expired - Fee Related
- 2012-08-10 TW TW101128885A patent/TWI568731B/zh not_active IP Right Cessation
- 2012-08-10 HU HUE12746093A patent/HUE042978T2/hu unknown
- 2012-08-10 PE PE2014000186A patent/PE20141410A1/es active IP Right Grant
- 2012-08-10 US US14/237,862 patent/US8906923B2/en active Active
- 2012-08-10 CN CN201280038643.4A patent/CN103874698B/zh active Active
- 2012-08-10 ES ES12746093T patent/ES2721658T3/es active Active
- 2012-08-10 WO PCT/EP2012/065733 patent/WO2013021054A1/en not_active Ceased
- 2012-08-10 TR TR2019/05537T patent/TR201905537T4/tr unknown
- 2012-08-10 EP EP12746093.9A patent/EP2742045B1/en active Active
- 2012-08-10 DK DK12746093.9T patent/DK2742045T3/en active
- 2012-08-10 CN CN201511000870.XA patent/CN105461684B/zh active Active
- 2012-10-08 UA UAA201400628A patent/UA111210C2/uk unknown
2014
- 2014-01-20 IL IL230549A patent/IL230549A/en active IP Right Grant
- 2014-02-05 CL CL2014000289A patent/CL2014000289A1/es unknown
- 2014-11-24 US US14/552,108 patent/US9290493B2/en active Active
2016
- 2016-03-16 US US15/071,612 patent/US9617262B2/en active Active
- 2016-04-12 JP JP2016079689A patent/JP2016190843A/ja not_active Withdrawn
2017
- 2017-03-09 US US15/454,703 patent/US9884864B2/en not_active Expired - Fee Related
- 2017-12-18 US US15/845,854 patent/US10155759B2/en active Active
2018
- 2018-11-16 US US16/194,052 patent/US10501463B2/en active Active
2019
- 2019-02-26 US US16/286,383 patent/US10526331B2/en active Active

Also Published As

Publication number	Publication date
AU2012293621B2 (en)	2016-07-21
TW201313714A (zh)	2013-04-01
US10526331B2 (en)	2020-01-07
UA111210C2 (uk)	2016-04-11
CN103874698B (zh)	2016-03-23
PE20141410A1 (es)	2014-10-13
JP5921687B2 (ja)	2016-05-24
HK1199243A1 (zh)	2015-06-26
US9884864B2 (en)	2018-02-06
ES2721658T3 (es)	2019-08-02
JP2014531404A (ja)	2014-11-27
CN103874698A (zh)	2014-06-18
JP2016190843A (ja)	2016-11-10
IL230549A (en)	2017-07-31
EP2742045B1 (en)	2019-01-23
CA2842518A1 (en)	2013-02-14
CN105461684B (zh)	2018-09-25
BR112014003063A2 (pt)	2017-02-21
US20190084982A1 (en)	2019-03-21
US20150080413A1 (en)	2015-03-19
BR112014003063B1 (pt)	2020-11-17
US20190194194A1 (en)	2019-06-27
US10501463B2 (en)	2019-12-10
EP2742045A1 (en)	2014-06-18
CL2014000289A1 (es)	2014-07-11
AU2012293621A1 (en)	2014-02-13
IL230549A0 (en)	2014-03-31
KR20140072034A (ko)	2014-06-12
US10155759B2 (en)	2018-12-18
EA201490438A1 (ru)	2014-06-30
US9617262B2 (en)	2017-04-11
UY34253A (es)	2013-02-28
CN105461684A (zh)	2016-04-06
US20180105525A1 (en)	2018-04-19
JO3611B1 (ar)	2020-08-27
AR087508A1 (es)	2014-03-26
CA2842518C (en)	2019-07-23
US20160194324A1 (en)	2016-07-07
TWI568731B (zh)	2017-02-01
KR101996862B1 (ko)	2019-07-05
TR201905537T4 (tr)	2019-05-21
WO2013021054A1 (en)	2013-02-14
PH12014500317A1 (en)	2014-04-14
US8906923B2 (en)	2014-12-09
HUE042978T2 (hu)	2019-07-29
US9290493B2 (en)	2016-03-22
US20170174683A1 (en)	2017-06-22
MX2014001600A (es)	2014-04-25
NZ620212A (en)	2015-10-30
HK1223352A1 (zh)	2017-07-28
US20140171451A1 (en)	2014-06-19
MX348128B (es)	2017-05-26

Publication	Publication Date	Title
DK2742045T3 (en)	2019-04-23	ANTIBACTERIAL CYCLOPENTA [C] PYRROL-SUBSTITUTED 3,4-DIHYDRO-1H- [1,8] NAPHTHYRIDINONES
AU2012293619B2 (en)	2017-05-04	Antibacterial piperidinyl substituted 3,4-dihydro-1h-[1,8]naphthyridinones
AU2012293618B2 (en)	2017-04-20	Antibacterial homopiperidinyl substituted 3,4 dihydro 1H (1,8)naphthyridinones
HK1223352B (zh)	2019-11-01	抗菌的环戊二烯并[c]吡咯取代的3，4-二氢-1h-[1，8]萘啶酮
EA043636B1 (ru)	2023-06-07	АНТИБАКТЕРИАЛЬНЫЕ 3,4-ДИГИДРО-1Н-[1,8]НАФТИРИДИНОНЫ, ЗАМЕЩЕННЫЕ ЦИКЛОПЕНТА[с]ПИРРОЛОМ