TWI631127B - 巨環廣效抗生素 - Google Patents

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Publication number

TWI631127B

TWI631127B TW102142527A TW102142527A TWI631127B TW I631127 B TWI631127 B TW I631127B TW 102142527 A TW102142527 A TW 102142527A TW 102142527 A TW102142527 A TW 102142527A TW I631127 B TWI631127 B TW I631127B

Authority

TW

Taiwan

Prior art keywords

formula

compound

alkyl

another embodiment

group

Prior art date

2012-11-21

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• 239000003242 anti bacterial agent Substances 0.000 title description 7
• 229940088710 antibiotic agent Drugs 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 1084
• 241000894006 Bacteria Species 0.000 claims abstract description 98
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 307
• 125000000217 alkyl group Chemical group 0.000 claims description 264
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 216
• 125000001072 heteroaryl group Chemical group 0.000 claims description 209
• 125000004432 carbon atom Chemical group C* 0.000 claims description 181
• 229910052739 hydrogen Inorganic materials 0.000 claims description 172
• 125000003118 aryl group Chemical group 0.000 claims description 143
• 229910052799 carbon Inorganic materials 0.000 claims description 123
• 239000001257 hydrogen Substances 0.000 claims description 120
• 125000000623 heterocyclic group Chemical group 0.000 claims description 110
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 94
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 73
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 69
• 150000003839 salts Chemical class 0.000 claims description 67
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
• 125000003342 alkenyl group Chemical group 0.000 claims description 62
• 125000000304 alkynyl group Chemical group 0.000 claims description 61
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 55
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 52
• 229910052760 oxygen Inorganic materials 0.000 claims description 47
• 239000003814 drug Substances 0.000 claims description 45
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 44
• 229910052717 sulfur Inorganic materials 0.000 claims description 42
• 125000001424 substituent group Chemical group 0.000 claims description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
• 125000005843 halogen group Chemical group 0.000 claims description 38
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 28
• 208000035143 Bacterial infection Diseases 0.000 claims description 27
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• 208000022362 bacterial infectious disease Diseases 0.000 claims description 27
• 229910052736 halogen Inorganic materials 0.000 claims description 26
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
• 229910052794 bromium Inorganic materials 0.000 claims description 25
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 24
• 229910052801 chlorine Inorganic materials 0.000 claims description 24
• 229910052731 fluorine Inorganic materials 0.000 claims description 24
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• 125000000547 substituted alkyl group Chemical group 0.000 claims description 18
• 229910052740 iodine Inorganic materials 0.000 claims description 17
• 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 16
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 16
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
• 125000003277 amino group Chemical group 0.000 claims description 15
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• TYZROVQLWOKYKF-ZDUSSCGKSA-N linezolid Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCOCC1 TYZROVQLWOKYKF-ZDUSSCGKSA-N 0.000 claims description 6
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• MINDHVHHQZYEEK-UHFFFAOYSA-N (E)-(2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-(beta)-methyl-2H-pyran-2-crotonic acid ester with 9-hydroxynonanoic acid Natural products CC(O)C(C)C1OC1CC1C(O)C(O)C(CC(C)=CC(=O)OCCCCCCCCC(O)=O)OC1 MINDHVHHQZYEEK-UHFFFAOYSA-N 0.000 claims description 4
• 241000589291 Acinetobacter Species 0.000 claims description 4
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• 108010013198 Daptomycin Proteins 0.000 claims description 4
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• 241000207201 Gardnerella vaginalis Species 0.000 claims description 4
• 241000606788 Haemophilus haemolyticus Species 0.000 claims description 4
• 241000606822 Haemophilus parahaemolyticus Species 0.000 claims description 4
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• 241000588915 Klebsiella aerogenes Species 0.000 claims description 4
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• 241000186779 Listeria monocytogenes Species 0.000 claims description 4
• 241000588621 Moraxella Species 0.000 claims description 4
• 241000588772 Morganella morganii Species 0.000 claims description 4
• 241000186367 Mycobacterium avium Species 0.000 claims description 4
• 241000186364 Mycobacterium intracellulare Species 0.000 claims description 4
• 241000186362 Mycobacterium leprae Species 0.000 claims description 4
• 241000588770 Proteus mirabilis Species 0.000 claims description 4
• 241000589540 Pseudomonas fluorescens Species 0.000 claims description 4
• 241000589776 Pseudomonas putida Species 0.000 claims description 4
• 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 claims description 4
• 241000531795 Salmonella enterica subsp. enterica serovar Paratyphi A Species 0.000 claims description 4
• 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 claims description 4
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 claims description 4
• 241000607715 Serratia marcescens Species 0.000 claims description 4
• 241000607764 Shigella dysenteriae Species 0.000 claims description 4
• 241000607762 Shigella flexneri Species 0.000 claims description 4
• 241000193985 Streptococcus agalactiae Species 0.000 claims description 4
• 241000607272 Vibrio parahaemolyticus Species 0.000 claims description 4
• 241000607447 Yersinia enterocolitica Species 0.000 claims description 4
• 241000607479 Yersinia pestis Species 0.000 claims description 4
• 241000607477 Yersinia pseudotuberculosis Species 0.000 claims description 4
• 229940126574 aminoglycoside antibiotic Drugs 0.000 claims description 4
• 239000002647 aminoglycoside antibiotic agent Substances 0.000 claims description 4
• WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 4
• 229960005091 chloramphenicol Drugs 0.000 claims description 4
• DOAKLVKFURWEDJ-QCMAZARJSA-N daptomycin Chemical compound C([C@H]1C(=O)O[C@H](C)[C@@H](C(NCC(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@H](CO)C(=O)N[C@H](C(=O)N1)[C@H](C)CC(O)=O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCCCCCCCC)C(=O)C1=CC=CC=C1N DOAKLVKFURWEDJ-QCMAZARJSA-N 0.000 claims description 4
• 229960005484 daptomycin Drugs 0.000 claims description 4
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• 229960003128 mupirocin Drugs 0.000 claims description 4
• 229930187697 mupirocin Natural products 0.000 claims description 4
• DDHVILIIHBIMQU-YJGQQKNPSA-L mupirocin calcium hydrate Chemical compound O.O.[Ca+2].C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1.C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1 DDHVILIIHBIMQU-YJGQQKNPSA-L 0.000 claims description 4
• 150000002960 penicillins Chemical class 0.000 claims description 4
• 239000003910 polypeptide antibiotic agent Substances 0.000 claims description 4
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• 229960001225 rifampicin Drugs 0.000 claims description 4
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• CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 claims description 2
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