NZ740037B2 - New effective aminoglycoside antibiotic for multidrug-resistant bacteria - Google Patents
New effective aminoglycoside antibiotic for multidrug-resistant bacteria Download PDFInfo
- Publication number
- NZ740037B2 NZ740037B2 NZ740037A NZ74003716A NZ740037B2 NZ 740037 B2 NZ740037 B2 NZ 740037B2 NZ 740037 A NZ740037 A NZ 740037A NZ 74003716 A NZ74003716 A NZ 74003716A NZ 740037 B2 NZ740037 B2 NZ 740037B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- group
- hydrogen atom
- amino
- hydroxyl
- solvate
- Prior art date
Links
- 241000894006 Bacteria Species 0.000 title abstract 3
- 229940126574 aminoglycoside antibiotic Drugs 0.000 title 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 19
- 150000003839 salts Chemical class 0.000 claims abstract 15
- 239000012453 solvate Substances 0.000 claims abstract 14
- 208000035473 Communicable disease Diseases 0.000 claims abstract 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 5
- 230000002265 prevention Effects 0.000 claims abstract 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 28
- 125000003277 amino group Chemical group 0.000 claims 21
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 208000015181 infectious disease Diseases 0.000 claims 9
- 125000005843 halogen group Chemical group 0.000 claims 8
- XZNUGFQTQHRASN-XQENGBIVSA-N apramycin Chemical compound O([C@H]1O[C@@H]2[C@H](O)[C@@H]([C@H](O[C@H]2C[C@H]1N)O[C@@H]1[C@@H]([C@@H](O)[C@H](N)[C@@H](CO)O1)O)NC)[C@@H]1[C@@H](N)C[C@@H](N)[C@H](O)[C@H]1O XZNUGFQTQHRASN-XQENGBIVSA-N 0.000 claims 6
- 229950006334 apramycin Drugs 0.000 claims 6
- -1 L-isoseryl group Chemical group 0.000 claims 4
- 125000000988 D-alanyl group Chemical group N[C@@H](C(=O)*)C 0.000 claims 2
- 125000000722 D-seryl group Chemical group N[C@@H](C(=O)*)CO 0.000 claims 2
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims 2
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 claims 2
- 241000191967 Staphylococcus aureus Species 0.000 claims 2
- 208000031650 Surgical Wound Infection Diseases 0.000 claims 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 2
- 241000588724 Escherichia coli Species 0.000 claims 1
- 241000588747 Klebsiella pneumoniae Species 0.000 claims 1
- 201000009906 Meningitis Diseases 0.000 claims 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims 1
- 206010057190 Respiratory tract infections Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 201000007119 infective endocarditis Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229960003085 meticillin Drugs 0.000 claims 1
- 230000000399 orthopedic effect Effects 0.000 claims 1
- 206010034674 peritonitis Diseases 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 208000019206 urinary tract infection Diseases 0.000 claims 1
- 241000192125 Firmicutes Species 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/12—Acyclic radicals, not substituted by cyclic structures attached to a nitrogen atom of the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/224—Cyclohexane rings substituted by at least two nitrogen atoms with only one saccharide radical directly attached to the cyclohexyl radical, e.g. destomycin, fortimicin, neamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Disclosed are: a compound represented by general formula (I), or a pharmaceutically acceptable salt of the compound, or a solvate of the compound or the pharmaceutically acceptable salt; a pharmaceutical composition containing the compound, the pharmaceutically acceptable salt or the solvate; a use of the compound, the pharmaceutically acceptable salt or the solvate for the prevention or treatment of infectious diseases; and a method for preventing or treating infectious diseases using the compound, the pharmaceutically acceptable salt or the solvate. The compound represented by general formula (I) has an antibacterial activity against both gram-positive bacteria and gram-negative bacteria, and is therefore useful for the prevention or treatment of infectious diseases induced by these bacteria.
Claims (14)
1. A compound represented by a general formula (I) or a pharmaceutically acceptable salt or solvate thereof: [Chem. 1] 5 (I) wherein, R is a hydrogen atom or a hydroxyl group, R is a hydrogen atom or an amino group, R is a hydrogen atom, a halogen atom, a hydroxyl group or an amino 10 group, R is a hydrogen atom, a halogen atom or an amino group, wherein R and R may form a double bond together, R is a hydrogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a hydroxyl group or an amino group, 15 R is a hydrogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a hydroxyl group or an amino group, R and R are each independently a hydrogen atom, a C alkyl group, an amino-C alkyl group, a guanidino-C alkyl group, an 1-6 1-6 amino-C cycloalkyl group, an amino-C cycloalkyl-C alkyl group, 3-7 3-7 1-6 20 an amidino group, an azetidino group optionally substituted with a C alkyl group, a glycyl group, a sarcosyl group, an L- alanyl group, a D-alanyl group, an L-seryl group, a D-seryl group, a ß-alanyl group, an L-isoseryl group or a D-isoseryl group; and R is a hydrogen atom, a hydroxyl group or a fluorine atom, 25 except when 5 8 11 1 2 3 4 6 7 9 (i) R , R , and R are hydroxyl groups, R , R , R , R , R , R , R , and R are hydrogen atoms, 1 5 8 11 2 3 4 6 7 9 (ii) R , R , R , and R are hydroxyl groups, R , R , R , R , R , R , and R are hydrogen atoms, 5 8 11 2 3 6 7 9 10 30 (iii) R , R and R are hydroxyl groups, R , R , R , R , R and R are hydrogen atoms, R and R form a double bond together.
2. The compound according to Claim 1 represented by formula (I-1) or a pharmaceutically acceptable salt or solvate thereof: [Chem. 2] (I-1) 5 wherein, R is a hydrogen atom or a hydroxyl group, R is a hydrogen atom or an amino group, R is a hydrogen atom, a halogen atom, a hydroxyl group or an amino group, 10 R is a hydrogen atom, a halogen atom or an amino group, wherein R and R may form a double bond together, R is a hydrogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a hydroxyl group or an amino group, 15 R is a hydrogen atom, a hydroxyl group or an amino group; and R is a hydrogen atom, a hydroxyl group or a fluorine atom, except when 5 8 11 1 2 3 4 6 7 (i) R , R , and R are hydroxyl groups, R , R , R , R , R , and R are hydrogen atoms, 1 5 8 11 2 3 4 6 7 20 (ii) R , R , R , and R are hydroxyl groups, R , R , R , R , and R are hydrogen atoms, 5 8 11 2 3 6 7 (iii) R , R and R are hydroxyl groups, R , R , R and R are hydrogen atoms, R and R form a double bond together.
3. The compound according to Claim 1 represented by a general 25 formula (I-2) or a pharmaceutically acceptable salt or solvate thereof: [Chem. 3] (I-2) wherein, R is a hydrogen atom or a hydroxyl group, R is a hydrogen atom or an amino group, 5 R is a hydrogen atom, a halogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a halogen atom or an amino group, wherein R and R may form a double bond together, R is a hydrogen atom, a hydroxyl group or an amino group, 10 R is a hydrogen atom, a hydroxyl group or an amino group, R is a hydrogen atom, a C alkyl group or an amino-C alkyl 1-6 1-6 group, R is a C alkyl group, an amino-C alkyl group, a guanidino-C 1-6 1-6 1-6 alkyl group, an amino-C cycloalkyl group, an amino-C 3-7 3-7 15 cycloalkyl-C alkyl group, an amidino group, an azetidino group optionally substituted with a C alkyl group, a glycyl group, a sarcosyl group, an L- alanyl group, a D-alanyl group, an L-seryl group, a D-seryl group, a ß-alanyl group, an L-isoseryl group or a D-isoseryl group; and 20 R is a hydrogen atom or a hydroxyl group.
4. The compound according to Claim 1 represented by a general formula (I-4) or a pharmaceutically acceptable salt or solvate thereof: [Chem. 5] 25 (I-4) wherein, R is a hydrogen atom or a hydroxyl group, R is a hydrogen atom or an amino group, R is a hydrogen atom, a halogen atom, a hydroxyl group or an amino group, 5 R is a hydrogen atom, a halogen atom or an amino group; and wherein R and R may form a double bond together, except when 1 2 3 4 (i) R , R , R , and R are hydrogen atoms, 1 2 3 4 (ii) R is a hydroxyl group, and R , R , and R are hydrogen atoms, 2 3 1 4 10 (iii) R and R are hydrogen atoms, R and R form a double bond together.
5. A compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is: 5-epiapramycin, 15 5-deoxyepifluoroapramycin, 6-deoxyepiapramycin, 5,6-dideoxyfluoroapramycin, 5-aminodeoxyepiapramycin, 5-aminodeoxyapramycin, 20 6-amino-5,6-dideoxy-5,6-diepifluoroapramycin, 5-amino-5,6-dideoxyapramycin, 5,6"-dideoxyapramycin, 5,3"-dideoxyapramycin, 3"-deoxyepiapramycin, 25 5,3"-dideoxyepifluoroapramycin, 6,3"-dideoxyepiapramycin, 5,6,3"-trideoxyapramycin, 5-amino-5,3"-dideoxyepiapramycin, 5,2"-dideoxy-5,3"-diepifluoroapramycin, 30 5,3"-diepiapramycin, 6,6"-dideoxyepiapramycin, 5-eno-5,6,6"-trideoxyapramycin, 5,6,6"-trideoxyapramycin, 5-deoxy-4"-N-methylapramycin, 35 4"-N-(2-aminoethyl)deoxyapramycin, 4"-N-(3-aminopropyl)deoxyapramycin, 5-deoxy-4"-N-(1,3-diaminopropanyl)apramycin, 4"-deaminodeoxy-4"-guanidinoapramycin, 5-epi-4"-N-methylapramycin, 4"-N-(2-aminoethyl)epiapramycin, 5 4"-N-(3-aminopropyl)epiapramycin, 4"-N-(1,3-diaminopropanyl)epiapramycin, 4"-deaminoepi-4"-guanidinoapramycin, 4"-deaminodeoxyepifluoro-4"-guanidinoapramycin, 5,6-dideoxy-4"-N-methylapramycin, 10 4"-N-(2-aminoethyl)-5,6-dideoxyapramycin, 4"-N-(3-aminopropyl)-5,6-dideoxyapramycin, 4"-N-(1,3-diaminopropanyl)-5,6-dideoxyapramycin, 4"-deamino-5,6-dideoxy-4"-guanidinoapramycin, 6-deoxyepi-4"-N-methylapramycin, 15 4"-N-(2-aminoethyl)deoxyepiapramycin, 4"-N-(3-aminopropyl)deoxyepiapramycin, 4"-deaminodeoxyepi-4"-guanidinoapramycin, 4"-N-(1,3-diaminopropanyl)-5,6"-dideoxyapramycin, 4"-deamino-5,6"-dideoxy-4"-guanidinoapramycin, 20 4"-deamino-5,3"-dideoxy-4"-guanidinoapramycin, 5-epi-4"-N-glycylapramycin, 5-epi-4"-N-sarcosylapramycin, 4"-N-(L-alanyl)epiapramycin, 5-epi-4"-N-(L-seryl)apramycin, 25 4"-N-(ß-alanyl)epiapramycin, 5-epi-4"-N-(L-isoseryl)apramycin, 5-epi-4"-N-(D-isoseryl)apramycin, 6-deoxyepi-4"-N-glycylapramycin, 6-deoxyepi-4"-N-sarcosylapramycin, 30 4"-N-(ß-alanyl)deoxyepiapramycin, 6-deoxyepi-4"-N-(L-isoseryl)apramycin, 5-amino-4"-deaminodeoxyepi-4"-guanidinoapramycin, 5-aminodeoxyepi-4"-N-glycylapramycin, 5-aminodeoxyepi-4"-N-(L-isoseryl)apramycin, 35 4"-deamino-3"-deoxyepi-4"-guanidinoapramycin, 4"-deamino-5,3"-dideoxyepifluoro-4"-guanidinoapramycin 2"-deoxy-5,3"-diepiapramycin.
6. A pharmaceutical composition comprising the compound according to any one of Claims 1 to 5 or a pharmaceutically 5 acceptable salt or solvate thereof.
7. The pharmaceutical composition according to Claim 6 for use in the prevention or treatment of infectious disease.
8. The pharmaceutical composition according to Claim 7, wherein the infectious disease is sepsis, infectious endocarditis, dermatological 10 infections, surgical site infections, orthopedic surgical site infections, respiratory infections, urinary tract infections, enteral infections, peritonitis, meningitis, ophthalmological infections or otolaryngological infections.
9. The pharmaceutical composition according to any one of Claims 7 15 or 8, wherein the infectious disease is caused by methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa.
10. The compound according to any one of Claims 1 to 5 or a pharmaceutically acceptable salt or solvate thereof for use in 20 therapy.
11. The compound according to any one of Claims 1 to 5 or a pharmaceutically acceptable salt or solvate thereof for use in the prevention or treatment of infectious disease.
12. Use of the compound according to any one of Claims 1 to 5 or a 25 pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the prevention or treatment of infectious disease.
13. An antimicrobial agent comprising the compound of any one of Claims 1 to 5 or a pharmaceutically acceptable salt or solvate thereof. 30
14. The compound according to claim 1, substantially as herein described with reference to any one of the Examples thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015151250 | 2015-07-30 | ||
| PCT/JP2016/072400 WO2017018528A1 (en) | 2015-07-30 | 2016-07-29 | Novel aminoglycoside antibiotic effective against multidrug-resistant bacteria |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ740037A NZ740037A (en) | 2024-08-30 |
| NZ740037B2 true NZ740037B2 (en) | 2024-12-03 |
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