JP2018502845A5 - - Google Patents
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- JP2018502845A5 JP2018502845A5 JP2017532053A JP2017532053A JP2018502845A5 JP 2018502845 A5 JP2018502845 A5 JP 2018502845A5 JP 2017532053 A JP2017532053 A JP 2017532053A JP 2017532053 A JP2017532053 A JP 2017532053A JP 2018502845 A5 JP2018502845 A5 JP 2018502845A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- atoms
- biaryl
- atom
- 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.)
- Granted
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- 125000000217 alkyl group Chemical group 0.000 claims description 141
- 150000001875 compounds Chemical class 0.000 claims description 108
- 125000003118 aryl group Chemical group 0.000 claims description 64
- 125000004429 atom Chemical group 0.000 claims description 63
- -1 tetrahydro-2H-pyran-2-one-3-yl Chemical group 0.000 claims description 57
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000002883 imidazolyl group Chemical group 0.000 claims description 19
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 17
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 241000588724 Escherichia coli Species 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- 241000588626 Acinetobacter baumannii Species 0.000 claims description 4
- 206010029155 Nephropathy toxic Diseases 0.000 claims description 4
- 108010093965 Polymyxin B Proteins 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 244000005700 microbiome Species 0.000 claims description 4
- 230000007694 nephrotoxicity Effects 0.000 claims description 4
- 231100000417 nephrotoxicity Toxicity 0.000 claims description 4
- 125000004437 phosphorous atom Chemical group 0.000 claims description 4
- 229920000024 polymyxin B Polymers 0.000 claims description 4
- 229960005266 polymyxin b Drugs 0.000 claims description 4
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 3
- 206010035664 Pneumonia Diseases 0.000 claims description 2
- 230000001332 colony forming effect Effects 0.000 claims description 2
- 125000005841 biaryl group Chemical group 0.000 claims 24
- 239000008194 pharmaceutical composition Substances 0.000 claims 9
- 230000000813 microbial effect Effects 0.000 claims 4
- 208000035143 Bacterial infection Diseases 0.000 claims 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 239000008280 blood Substances 0.000 claims 2
- 210000004369 blood Anatomy 0.000 claims 2
- 208000001860 Eye Infections Diseases 0.000 claims 1
- 206010062207 Mycobacterial infection Diseases 0.000 claims 1
- 206010031252 Osteomyelitis Diseases 0.000 claims 1
- 208000032536 Pseudomonas Infections Diseases 0.000 claims 1
- 206010057190 Respiratory tract infections Diseases 0.000 claims 1
- 206010062255 Soft tissue infection Diseases 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000011323 eye infectious disease Diseases 0.000 claims 1
- 208000027096 gram-negative bacterial infections Diseases 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 claims 1
- 230000002685 pulmonary effect Effects 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 206010040872 skin infection Diseases 0.000 claims 1
- 210000004872 soft tissue Anatomy 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 150000005347 biaryls Chemical group 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- 0 CCCC(N[C@@]([C@@](C)O)C(NC(*(C)C(C)CN)C(N[C@@](CCNC(C[C@@](C)O)=O)C(NCC(N[C@](*)C(NC1)=*=C1N[C@](*CN)C(NC(C)C(N)=O)=O)=O)=O)=O)=O)=O Chemical compound CCCC(N[C@@]([C@@](C)O)C(NC(*(C)C(C)CN)C(N[C@@](CCNC(C[C@@](C)O)=O)C(NCC(N[C@](*)C(NC1)=*=C1N[C@](*CN)C(NC(C)C(N)=O)=O)=O)=O)=O)=O)=O 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 108010040201 Polymyxins Proteins 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010078777 Colistin Proteins 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 229960003346 colistin Drugs 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 description 3
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 description 3
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IWMJTVFIXQQTJQ-KRWDZBQOSA-N (2S)-2-(2,6-difluoro-4-phenylbenzoyl)oxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound C(C)(C)(C)OC(=O)NCC[C@@H](C(=O)O)OC(=O)C1=C(C=C(C=C1F)C1=CC=CC=C1)F IWMJTVFIXQQTJQ-KRWDZBQOSA-N 0.000 description 2
- POASMXSJVKADPM-LURJTMIESA-N (2s)-2-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCC[C@H](O)C(O)=O POASMXSJVKADPM-LURJTMIESA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- OGYSYXDNLPNNPW-UHFFFAOYSA-N 4-butoxy-4-oxobutanoic acid Chemical compound CCCCOC(=O)CCC(O)=O OGYSYXDNLPNNPW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 108010069514 Cyclic Peptides Proteins 0.000 description 2
- 102000001189 Cyclic Peptides Human genes 0.000 description 2
- 241000606768 Haemophilus influenzae Species 0.000 description 2
- 208000032376 Lung infection Diseases 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- 108700026839 polymyxin B nonapeptide Proteins 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- GNQAQRVZTYEXPJ-SLTAFYQDSA-N (2S)-6-butan-2-yloxycarbonyl-4-[(2-methylpropan-2-yl)oxycarbonyl]-1-(2-methylpropyl)piperazine-2-carboxylic acid Chemical compound C(C)(CC)OC(=O)C1CN(C[C@H](N1CC(C)C)C(=O)O)C(=O)OC(C)(C)C GNQAQRVZTYEXPJ-SLTAFYQDSA-N 0.000 description 1
- PYHYGIPVYYRJHU-QWDNBKTCSA-N (2s,3r)-2-amino-n-[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1r)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]-3-hydroxybutanamid Chemical compound N1C(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@@H](N)[C@@H](C)O)CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1CC1=CC=CC=C1 PYHYGIPVYYRJHU-QWDNBKTCSA-N 0.000 description 1
- PYHYGIPVYYRJHU-LPGHPFMSSA-N (2s,3r)-2-amino-n-[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15s,18s,21s)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1r)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]-3-hydroxybutanamid Polymers N1C(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@@H](N)[C@@H](C)O)CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CC1=CC=CC=C1 PYHYGIPVYYRJHU-LPGHPFMSSA-N 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- JGRCHNVLXORPNM-UHFFFAOYSA-N 1,2-oxazol-4-one Chemical compound O=C1CON=C1 JGRCHNVLXORPNM-UHFFFAOYSA-N 0.000 description 1
- OQKYGBNJIBWJQS-UHFFFAOYSA-N 1,3-benzoxazin-4-one Chemical compound C1=CC=C2C(=O)N=COC2=C1 OQKYGBNJIBWJQS-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- REFAMVPQJHXFFM-UHFFFAOYSA-N 1,3-oxazepan-2-one Chemical compound O=C1NCCCCO1 REFAMVPQJHXFFM-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- PDEIXVFSDKHCOC-UHFFFAOYSA-N 1,4-oxazepan-2-one Chemical compound O=C1CNCCCO1 PDEIXVFSDKHCOC-UHFFFAOYSA-N 0.000 description 1
- YNHIMQYJCDVCEG-UHFFFAOYSA-N 1,4-oxazepan-3-one Chemical compound O=C1COCCCN1 YNHIMQYJCDVCEG-UHFFFAOYSA-N 0.000 description 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 1
- HZONRRHNQILCNO-UHFFFAOYSA-N 1-methyl-2h-pyridine Chemical compound CN1CC=CC=C1 HZONRRHNQILCNO-UHFFFAOYSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical group CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- GCIIMLMWDVTTTN-UHFFFAOYSA-N 2,6-difluoro-4-phenylbenzoyl chloride Chemical compound C1(=CC=CC=C1)C1=CC(=C(C(=O)Cl)C(=C1)F)F GCIIMLMWDVTTTN-UHFFFAOYSA-N 0.000 description 1
- UGOCHLDEQFMDFI-UHFFFAOYSA-N 2-(3-chlorobenzoyl)oxypyridine-4-carboxylic acid Chemical compound ClC=1C=C(C(=O)OC=2C=C(C(=O)O)C=CN=2)C=CC=1 UGOCHLDEQFMDFI-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- OULDXTKXFJQCEW-UHFFFAOYSA-N 2-dibutoxyphosphoryl-2,2-difluoroacetic acid Chemical compound C(CCC)OP(=O)(OCCCC)C(C(=O)O)(F)F OULDXTKXFJQCEW-UHFFFAOYSA-N 0.000 description 1
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| JP6643758B2 (ja) | 2013-05-22 | 2020-02-12 | スペロ・セラピューティクス・インコーポレーテッド | 異なった抗生物質と一緒の組合せ療法におけるポリミキシン誘導体及びその使用 |
| WO2015031602A1 (en) | 2013-08-29 | 2015-03-05 | Rhk Technology, Inc. | Optical alignment interface |
| RU2740190C2 (ru) * | 2014-03-11 | 2021-01-12 | Сперо Терапьютикс, Инк. | Производные полимиксина и их применение в комбинированной терапии совместно с различными антибиотиками |
| US10047126B2 (en) | 2014-04-01 | 2018-08-14 | Monash University | Polymyxin derivatives as antimicrobial compounds |
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2015
- 2015-12-16 US US14/972,031 patent/US9771394B2/en active Active
- 2015-12-16 ES ES15840980T patent/ES2924058T3/es active Active
- 2015-12-16 WO PCT/US2015/066210 patent/WO2016100578A2/en not_active Ceased
- 2015-12-16 JP JP2017532053A patent/JP6896628B2/ja active Active
- 2015-12-16 KR KR1020177019383A patent/KR102585108B1/ko active Active
- 2015-12-16 CA CA2970546A patent/CA2970546A1/en active Pending
- 2015-12-16 EP EP15840980.5A patent/EP3233889B1/en active Active
- 2015-12-16 CN CN201580075652.4A patent/CN107257803B/zh active Active
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