NZ741027B2 - Antimicrobial polymyxin derivative compounds - Google Patents
Antimicrobial polymyxin derivative compounds Download PDFInfo
- Publication number
- NZ741027B2 NZ741027B2 NZ741027A NZ74102716A NZ741027B2 NZ 741027 B2 NZ741027 B2 NZ 741027B2 NZ 741027 A NZ741027 A NZ 741027A NZ 74102716 A NZ74102716 A NZ 74102716A NZ 741027 B2 NZ741027 B2 NZ 741027B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- trifluoromethyl
- compound
- carboxyl
- gram
- picolinoyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract 11
- 108010040201 Polymyxins Proteins 0.000 title abstract 3
- 230000000845 anti-microbial effect Effects 0.000 title abstract 2
- 208000027096 gram-negative bacterial infections Diseases 0.000 claims abstract 7
- 239000003242 anti bacterial agent Substances 0.000 claims abstract 4
- -1 5-chloronicotinoyl Chemical group 0.000 claims 37
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims 5
- 150000001413 amino acids Chemical class 0.000 claims 4
- 125000005605 benzo group Chemical group 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims 3
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 claims 3
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 3
- 235000001014 amino acid Nutrition 0.000 claims 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 claims 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 2
- 239000004473 Threonine Substances 0.000 claims 2
- 235000004279 alanine Nutrition 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 2
- 239000004474 valine Substances 0.000 claims 2
- BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical group CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 claims 1
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 claims 1
- 150000008574 D-amino acids Chemical class 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 238000011260 co-administration Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 229940088710 antibiotic agent Drugs 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/60—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation occurring through the 4-amino group of 2,4-diamino-butanoic acid
- C07K7/62—Polymyxins; Related peptides
-
- 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
The present invention relates to antimicrobial polymyxin derivative compounds and their uses, and in particular to peptide polymyxin antibiotics which may be used in the treatment of bacterial infections such as Gram negative bacterial infections, particularly those caused by multidrug-resistant (MDR) Gram negative bacterial infections.
Claims (10)
1. A compound of formula (I): wherein R1 is selected from 5-chloronicotinoyl, 6-chloronicotinoyl, 2,6-dichloronicotinoyl, 4,6- dicloronicotinoyl, 5,6-dichloronicotinoyl, 6-(trifluoromethyl)nicotinoyl, 3,5- dichloropicolinoyl, 4,6-dichloropicolinoyl, 5-phenylpicolinoyl, hlorophenyl)picolinoyl, 4-(6-chloropyridinyl)benzoyl, 5-(4-chlorophenyl)thiophenecarboxyl, 2,6- dichloroisonicotinoyl, 5-(trifluoromethyl)nicotinoyl, 4-(trifluoromethyl)picolinoyl, 3,5- dibromopicolinoyl, 5-bromonicotinoyl, 2-chloroisonicotinoyl, oisonicotinoyl, 4- chloropicolinoyl, fluoromethyl)isonicotinoyl, 2,6-dibromoisonicotinoyl, 3,5- dibromopicolinoyl, 5-methylnicotinoyl, 2-fluoroisonicotinoyl, 2- (trifluoromethyl)isonicotinoyl, 5-bromochloropicolinoyl, 3-chloroisonicotinoyl, 3-chloro (trifluoromethyl)picolinoyl, ropicolinoyl, 5-chloropicolinoyl, 5- (trifluoromethyl)picolinoyl, 2-chloromethylisonicotinoyl, 2-chloro (trifluoromethyl)nicotinoyl, 6-ethylnicotinoyl, 5-ethylpicolinoyl, ropicolinoyl, 6- (trifluoromethyl)picolinoyl, 2-(trifluoromethyl)pyrimidinecarboxyl, 2-quinoxalinecarboxyl, 1H-benzimidazolecarboxyl, 1-methylindolecarboxyl, 6-methyl-imidazo[1,2-a]pyridine- 2-carboxyl, benzo[b]thiophenecarboxyl, 1-methylindazolecarboxyl, 3- quinolinecarboxyl, benzothiazolecarboxyl, 1H-indazolecarboxyl, quinaldoyl, ole- 2-carboxyl, 1-methylbenzimidazolecarboxyl, 5-chloromethylindolecarboxyl, 5- chloro-1H-indolecarboxyl, 5,6-difluoro-1H-indolecarboxyl, 3-chlorobezo[b]thiophene- 2-carboxyl, 1-methylindoleacetyl, 1-methylindolecarboxyl, benzo[d]thiazolecarboxyl, 6-chlorobenzimidazolecarboxyl, benzo[b]thiazolepropanoyl, 2-phenylpyrimidine carboxyl, benzooxazolecarboxyl, benzo[d]isooxazolecarboxyl, 2,5-dibromothiphene yl, 4,5-dibromopyrrolecarboxyl, 5-bromothiophenecarboxyl, 4,5-dibromofuran carboxyl, 5-phenyl-1,2-oxazolecarboxyl, 5-phenyl-1,2,4-oxadiazolecarboxyl, 2-phenyl- 1H-imidazolecarboxyl, 4,5-dibromothiophenecarboxyl, 5-phenyl-1H-pyrazole carboxyl, 3,5-dibromothiophenecarboxyl, 5-(trifluoromethyl)thiophenecarboxyl, 3- phenyl-1,2-oxazolecarboxyl, othiophenecarboxyl, rothiophenecarboxyl, 4H-thieno[3,2-b]pyrrolecarboxyl, 2-bromo-1,3-thiazolecarboxyl, urancarboxyl, 4-bromomethylpyrrolecarboxyl, 5-(4-chlorophenyl)-1,2-oxazolecarboxyl, 5- bromothiophenecarboxyl, 4-bromopicolinoyl, 5-bromofurancarboxyl and indole R2 represents a side chain of the amino acid L-Dap; R3 represents a side chain of an amino acid selected from leucine, phenylalanine, norleucine, or norvaline; and R4 represents a side chain of an amino acid selected from alanine, threonine, valine or 2- aminobutyric acid; or a pharmaceutically acceptable salt thereof.
2. A compound of a (I): wherein the compound is selected from D-Lcu Abu D-Leu Ala nd No. -D-Leu Ah“ 'D-Leu Ab" D-Leu Abu , and pharmaceutically able salts thereof; wherein f or R2, R3, and R4, the amino acid side chain stereochemistry at these positions is taken to be in the L-configuration unless otherwise specified, D- indicates D-amino acids; Dap is diaminopropionic acid, Dab is diaminobutyric acid, Phe is phenylalanine; Thr is threonine; Ala is alanine, Val is valine; Abu is 2-aminobutyric acid; Nle is norleucine; and Nva is norvaline.
3. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or 2, or pharmaceutically acceptable salts thereof, er with at least one ceutically acceptable carrier or diluent.
4. Use of a compound according to claim 1 or 2, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention or treatment of a Gramnegative bacterial ion.
5. Use according to claim 4, wherein the Gram-negative bacterial infection is a multidrug-resistant (MDR) Gram-negative bacterial infection.
6. Use according to claim 4 or 5, wherein the ment comprises a second antibacterial agent.
7. Use according to claim 4 or 5, wherein the medicament is for co-administration with a second antibacterial agent.
8. A compound according to claim 1 or 2 for use in the tion or ent of a Gram-negative bacterial infection.
9. A compound for use according to claim 8, wherein the Gram-negative bacterial infection is a multidrug-resistant (MDR) Gram-negative bacterial infection.
10. A compound for use ing to claim 8 or 9, wherein the compound is for coadministration with a second antibacterial agent.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2015903961A AU2015903961A0 (en) | 2015-09-29 | Antimicrobial compounds | |
| PCT/AU2016/050915 WO2017054047A1 (en) | 2015-09-29 | 2016-09-29 | Antimicrobial polymyxin derivative compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ741027A NZ741027A (en) | 2024-05-31 |
| NZ741027B2 true NZ741027B2 (en) | 2024-09-03 |
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