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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| CN111690040A (zh) * | 2019-03-12 | 2020-09-22 | 上海来益生物药物研究开发中心有限责任公司 | 多粘菌素衍生物、其制备方法和应用 |
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| BRPI0715095B8 (pt) | 2006-08-11 | 2021-05-25 | Northern Antibiotics Oy | derivado de polimixina da fórmula geral (i); produto de combinação; composição farmacêutica; método para se sensibilizar bactérias gram-negativas a um agente antibacteriano; método para o desenvolvimento de antibióticos; método para a redução da toxicidade de polimixinas, octapeptinas naturais e seus derivados durante a aplicação das mesmas no tratamento de infecções em um indivíduo; método para melhorar as propriedades farmacocinéticas, de polimixinas, octapeptinas naturais e seus derivados; método para a sensibilização de bactérias gram-negativas clinicamente importantes a um complemento de mecanismo de defesa presente no soro; uso de um derivado; e processo para a preparação de um derivado de polimixina da fórmula (i). |
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| JP6334546B2 (ja) | 2012-10-18 | 2018-05-30 | ダウ グローバル テクノロジーズ エルエルシー | リン含有カルボン酸アルミニウム塩難燃剤 |
| CN103044529B (zh) * | 2012-12-06 | 2018-01-30 | 山东鲁抗医药股份有限公司 | 一种在硫酸多粘菌素b中提取b1单组份的方法 |
| KR20150107793A (ko) | 2013-01-11 | 2015-09-23 | 셀리아 파마슈티칼즈 에이피에스 | 폴리믹신, 조성물, 제조 방법 및 사용 방법 |
| CN103923190B (zh) | 2013-01-14 | 2018-04-03 | 上海医药工业研究院 | 从多黏菌素b的混合组分中分离纯化多黏菌素b1的方法 |
| KR102354902B1 (ko) * | 2013-05-22 | 2022-01-24 | 에버레스트 메디신즈 (싱가포르) 피티이. 리미티드 | 폴리믹신 유도체 및 상이한 항생제와의 조합 요법에 있어서의 이들의 용도 |
| WO2015031602A1 (en) | 2013-08-29 | 2015-03-05 | Rhk Technology, Inc. | Optical alignment interface |
| MX359104B (es) | 2014-03-11 | 2018-09-14 | New Pharma Licence Holdings Ltd | Derivados de polimixina y su uso en terapia de combinacion junto con diferentes antibioticos. |
| JP2017512818A (ja) | 2014-04-01 | 2017-05-25 | モナシュ、ユニバーシティＭｏｎａｓｈ Ｕｎｉｖｅｒｓｉｔｙ | 抗菌性化合物としてのポリミキシン誘導体 |
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2015
- 2015-12-16 WO PCT/US2015/066210 patent/WO2016100578A2/en not_active Ceased
- 2015-12-16 ES ES15840980T patent/ES2924058T3/es 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 KR KR1020177019383A patent/KR102585108B1/ko active Active
- 2015-12-16 JP JP2017532053A patent/JP6896628B2/ja active Active
- 2015-12-16 US US14/972,031 patent/US9771394B2/en active Active
- 2015-12-16 CN CN201580075652.4A patent/CN107257803B/zh active Active
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