JP2017517547A5 - - Google Patents
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- 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
- 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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- 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
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462011613P | 2014-06-13 | 2014-06-13 | |
| US62/011,613 | 2014-06-13 | ||
| PCT/US2015/035534 WO2015191988A1 (en) | 2014-06-13 | 2015-06-12 | Small molecule efflux pump inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017517547A JP2017517547A (ja) | 2017-06-29 |
| JP2017517547A5 true JP2017517547A5 (cg-RX-API-DMAC7.html) | 2018-06-07 |
| JP6678599B2 JP6678599B2 (ja) | 2020-04-08 |
Family
ID=53525251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016572622A Active JP6678599B2 (ja) | 2014-06-13 | 2015-06-12 | 小分子排出ポンプ阻害剤 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10471028B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP3154534B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6678599B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR20170015504A (cg-RX-API-DMAC7.html) |
| CN (1) | CN106573007A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2015274427B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2952111C (cg-RX-API-DMAC7.html) |
| WO (1) | WO2015191988A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9834514B2 (en) * | 2015-04-20 | 2017-12-05 | New Mexico Tech Research Foundation | Antibiotic sensitivity-restoring and photosensitive agents |
| EP3600331A4 (en) | 2017-03-27 | 2022-03-09 | The Regents of the University of Colorado, A Body Corporate | SMALL MOLECULE INHIBITORS OF BACTERIAL EFFLUX PUMPS AND METHODS OF USING SAME |
| CN107216305B (zh) * | 2017-05-03 | 2020-05-08 | 中国人民解放军第四军医大学 | 一类苯并吡喃类化合物及其应用 |
| EP3737664B8 (en) * | 2018-01-09 | 2024-07-17 | The Hong Kong Polytechnic University | Antimicrobial 2-[[(phenyl)imino]methyl]-4-nitro-phenol derivatives and related compounds as inhibitors of the nusb-nuse interaction of microorganisms for the treatment of bacterial infections |
| CN118084940A (zh) | 2018-02-13 | 2024-05-28 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| AU2019255750B2 (en) | 2018-04-19 | 2021-10-21 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| PE20210642A1 (es) | 2018-07-13 | 2021-03-23 | Gilead Sciences Inc | Inhibidores de pd-1/pd-l1 |
| EP3842439A4 (en) | 2018-08-21 | 2022-04-27 | Kyorin Pharmaceutical Co., Ltd. | Bicyclic heteroaromatic ring derivative |
| CN108822089A (zh) * | 2018-08-22 | 2018-11-16 | 大连理工大学 | 2-芳基咪唑烷类化合物、制备方法及其作为Hsp90抑制剂在抗肿瘤上的应用 |
| CN112955435B (zh) | 2018-10-24 | 2024-09-06 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| WO2023044364A1 (en) | 2021-09-15 | 2023-03-23 | Enko Chem, Inc. | Protoporphyrinogen oxidase inhibitors |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1188512A (zh) * | 1995-04-21 | 1998-07-22 | 迈克罗赛药品公司 | 外流泵抑制剂 |
| US5989832A (en) * | 1995-04-21 | 1999-11-23 | Microcide Pharmaceuticals, Inc. | Method for screening for non-tetracycline efflux pump inhibitors |
| US20030220338A1 (en) | 2001-07-16 | 2003-11-27 | Watkins Will J. | Fungal efflux pump inhibitors |
| AU2005259488B2 (en) * | 2004-06-30 | 2009-10-01 | Novartis Ag | Method for increasing the susceptibility of peptide deformylase inhibitors by using efflux pump inhibitors |
| FR2873692B1 (fr) * | 2004-07-29 | 2006-12-01 | Univ Claude Bernard Lyon | COMPOSITIONS CONTENANT, EN ASSOCIATION AVEC UN AGENT ANTIMICROBIEN, UN COMPOSE THIOPHENIQUE OU BENZOTHIOPHENIQUE DE FORMULE(I)PRESENTANT UNE ACTIVITE INHIBITRICE DE POMPE NorA |
| CA2686997A1 (en) * | 2007-05-11 | 2008-11-20 | Mpex Pharmaceuticals, Inc. | Quaternary alkyl ammonium bacterial efflux pump inhibitors and therapeutic uses thereof |
| CN101301289B (zh) * | 2008-05-22 | 2010-09-22 | 中国科学院微生物研究所 | 小檗碱及其结构类似物在逆转多药耐药泵中的应用 |
| WO2011006158A2 (en) | 2009-07-10 | 2011-01-13 | University Of Maryland, Baltimore | Targeting nad biosynthesis in bacterial pathogens |
| US8933018B2 (en) * | 2011-02-07 | 2015-01-13 | Rempex Pharmaceuticals, Inc. | Boron containing polybasic bacterial efflux pump inhibitors and therapeutic uses thereof |
| CN103156844B (zh) * | 2011-12-15 | 2016-11-16 | 天津市国际生物医药联合研究院 | 西弗碱类化合物在制备抑制ndm-1活性的药物中的应用 |
| AU2013302177A1 (en) * | 2012-08-10 | 2015-03-26 | Mcmaster University | Antibacterial inhibitors |
-
2015
- 2015-06-12 JP JP2016572622A patent/JP6678599B2/ja active Active
- 2015-06-12 KR KR1020177000672A patent/KR20170015504A/ko not_active Ceased
- 2015-06-12 CA CA2952111A patent/CA2952111C/en active Active
- 2015-06-12 AU AU2015274427A patent/AU2015274427B2/en active Active
- 2015-06-12 US US15/317,811 patent/US10471028B2/en active Active
- 2015-06-12 CN CN201580030544.5A patent/CN106573007A/zh active Pending
- 2015-06-12 EP EP15735770.8A patent/EP3154534B1/en active Active
- 2015-06-12 WO PCT/US2015/035534 patent/WO2015191988A1/en not_active Ceased