JP2017517547A5 - - Google Patents

Info

Publication number

JP2017517547A5

JP2017517547A5 JP2016572622A JP2016572622A JP2017517547A5 JP 2017517547 A5 JP2017517547 A5 JP 2017517547A5 JP 2016572622 A JP2016572622 A JP 2016572622A JP 2016572622 A JP2016572622 A JP 2016572622A JP 2017517547 A5 JP2017517547 A5 JP 2017517547A5

Authority

JP

Japan

Prior art keywords

substituted

unsubstituted

pharmaceutical composition

group

pump inhibitor

Prior art date

2015-06-12

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

Links

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• 239000003112 inhibitor Substances 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 43
• 125000003118 aryl group Chemical group 0.000 claims description 35
• 125000001072 heteroaryl group Chemical group 0.000 claims description 34
• 150000002431 hydrogen Chemical class 0.000 claims description 31
• 125000004104 aryloxy group Chemical group 0.000 claims description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 23
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 20
• 150000002367 halogens Chemical class 0.000 claims description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 239000004599 antimicrobial Substances 0.000 claims description 18
• 208000035143 Bacterial infection Diseases 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 15
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 15
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 208000015181 infectious disease Diseases 0.000 claims description 9
• 230000000813 microbial effect Effects 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 150000001409 amidines Chemical class 0.000 claims description 8
• 239000000651 prodrug Substances 0.000 claims description 8
• 229940002612 prodrug Drugs 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 8
• 241000589291 Acinetobacter Species 0.000 claims description 6
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
• 241000589516 Pseudomonas Species 0.000 claims description 6
• MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 6
• 208000027096 gram-negative bacterial infections Diseases 0.000 claims description 5
• 241000588626 Acinetobacter baumannii Species 0.000 claims description 3
• 108010078777 Colistin Proteins 0.000 claims description 3
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 3
• 229930182566 Gentamicin Natural products 0.000 claims description 3
• GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims description 3
• 108010093965 Polymyxin B Proteins 0.000 claims description 3
• 229960004821 amikacin Drugs 0.000 claims description 3
• LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 claims description 3
• 229960004755 ceftriaxone Drugs 0.000 claims description 3
• VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 3
• 229960003405 ciprofloxacin Drugs 0.000 claims description 3
• 229960003346 colistin Drugs 0.000 claims description 3
• 229960003276 erythromycin Drugs 0.000 claims description 3
• 229960002518 gentamicin Drugs 0.000 claims description 3
• 229960000318 kanamycin Drugs 0.000 claims description 3
• 229930027917 kanamycin Natural products 0.000 claims description 3
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 claims description 3
• 229930182823 kanamycin A Natural products 0.000 claims description 3
• 229960003376 levofloxacin Drugs 0.000 claims description 3
• 229960002260 meropenem Drugs 0.000 claims description 3
• DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 claims description 3
• 229960004023 minocycline Drugs 0.000 claims description 3
• DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical group C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 claims 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 claims description 3
• MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 claims description 3
• 229960000210 nalidixic acid Drugs 0.000 claims description 3
• 229920000024 polymyxin B Polymers 0.000 claims 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 claims 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 claims description 3
• 229960005266 polymyxin b Drugs 0.000 claims description 3
• 229960005404 sulfamethoxazole Drugs 0.000 claims description 3
• JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 claims description 3
• 229960004089 tigecycline Drugs 0.000 claims description 3
• FPZLLRFZJZRHSY-HJYUBDRYSA-N tigecycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=C(NC(=O)CNC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O FPZLLRFZJZRHSY-HJYUBDRYSA-N 0.000 claims description 3
• 229960000707 tobramycin Drugs 0.000 claims description 3
• NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 claims description 3
• 229960001082 trimethoprim Drugs 0.000 claims description 3
• IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims description 3
• 208000032536 Pseudomonas Infections Diseases 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims 1
• 230000001580 bacterial effect Effects 0.000 description 13
• 239000000203 mixture Substances 0.000 description 10
• 0 C*C1C(C)*CCC1C Chemical compound C*C1C(C)*CCC1C 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 3
• 125000005017 substituted alkenyl group Chemical group 0.000 description 3
• 125000000547 substituted alkyl group Chemical group 0.000 description 3
• 244000005700 microbiome Species 0.000 description 2
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 1