AR096370A1 - POLYMIXIN DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS - Google Patents

POLYMIXIN DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS

Info

Publication number
AR096370A1
AR096370A1 ARP140102014A ARP140102014A AR096370A1 AR 096370 A1 AR096370 A1 AR 096370A1 AR P140102014 A ARP140102014 A AR P140102014A AR P140102014 A ARP140102014 A AR P140102014A AR 096370 A1 AR096370 A1 AR 096370A1
Authority
AR
Argentina
Prior art keywords
alkyl
group
independently
groups
substituted
Prior art date
Application number
ARP140102014A
Other languages
Spanish (es)
Inventor
Brown Pamela
Dawson Michael
Simonovic Mona
Boakes Steven
Duperchy Esther
Original Assignee
Cantab Anti-Infectives Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Cantab Anti-Infectives Ltd filed Critical Cantab Anti-Infectives Ltd
Publication of AR096370A1 publication Critical patent/AR096370A1/en

Links

Landscapes

  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Derivados de polimixina para su uso en un tratamiento combinado con un segundo principio activo, tal como rifampicina, por ejemplo para el tratamiento de una infección microbiana. Reivindicación 1: Un compuesto de polimixina para su uso en un método de tratamiento o profilaxis, en combinación con un principio activo, donde el principio activo es seleccionado del grupo que consiste en: rifampicina, rifabutina, rifalacilo, rifapentina y rifaximina; oxacilina, meticilina, ampicilina, cloxacilina, carbenicilina, piperacilina,tricarcilina, flucloxacilina y nafcilina; azitromicina, claritromicina, eritromicina, telitromicina, cetromicina y solitromicina; aztreonam y BAL30072; meropenem, doripenem, imipenem, ertapenem, biapenem, tomopenem y panipenem; tigeciclina, omadaciclina, eravaciclina, doxiciclina y minociclina; ciprofloxacina, levofloxacina, moxifloxacina y delafloxacina; acido fusidico; novobiocina; teichoplanina, telavancina, dalbavancina y oritavancina, y sales y solvatos del mismo aceptables para uso farmacéutico; y el compuesto de polimixina es un compuesto de la fórmula (1) y sales y solvatos del mismo aceptables para uso farmacéutico, donde: X es -C(O)-, -NHC(O)-, -OC(O)-, -CH₂- o -SO₂-; y R¹ junto con el grupo carbonilo y nitrógeno a del carbono al que está unido, es un resto fenilalanina, leucina o valina; R² junto con el grupo carbonilo y nitrógeno a del carbono al que está unido, es un resto leucina, treonina, iso-leucina, fenilalanina, valina o nor-valina; R³ junto con el grupo carbonilo y nitrógeno a del carbono al que está unido, es un resto treonina o leucina; R⁴ es alquilo C₁₋₆ sustituido con un grupo hidroxilo o un grupo amino; A es un enlace covalente o un aminoácido, tal como un a-aminoácido; R⁵ es G-L²-L¹-, G es seleccionado de: alquilo C₂₋₁₂, arilo C₅₋₁₂, cicloalquilo C₃₋₁₀, L¹ es un enlace covalente, alquileno C₁₋₁₂ o heteroalquileno C₂₋₁₂, L² es un enlace covalente o heterociclileno C₄₋₁₀, con la salvedad que L¹ no sea alquileno C₁₋₁₂ cuando G es alquilo C₂₋₁₂, y G-L²-L¹ está sustituido con: (i) uno, dos o tres grupos hidroxilo o (ii) uno, dos o tres grupos -NR⁶R⁷ o (iii) uno o dos grupos -NR⁶R⁷ y uno, dos o tres grupos hidroxilo, con la salvedad que (i), (ii) y (iii) son sustituyentes opcionales cuando L¹ es un heteroalquileno C₂₋₁₂ que contiene nitrógeno y/o L² es un heterociclileno C₄₋₁₀ que contiene nitrógeno, o R⁵ es D-L¹, donde D es heterociclilo C₄₋₁₀ y L¹ es como se definió antes y D-L¹- está sustituido con: (i) uno, dos o tres grupos hidroxilo o (ii) uno, dos o tres grupos -NR⁶R⁷ o (iii) uno o dos grupos -NR⁶R⁷ y uno, dos o tres grupos hidroxilo, con la salvedad que (i), (ii) y (iii) son sustituyentes opcionales cuando L¹ es un heteroalquileno C₂₋₁₂ que contiene nitrógeno y/o D es un heterociclilo C₄₋₁₀ que contiene nitrógeno, cada R⁶ es independientemente hidrógeno o alquilo C₁₋₄; cada R⁷ es independientemente hidrógeno o alquilo C₁₋₄; o NR⁶R⁷ es un grupo guanidina; o cuando G es cicloalquilo C₃₋₁₀ o arilo C₅₋₁₂, R⁶ y R⁷ junto con el átomo de nitrógeno de un heterociclo C₄₋₁₀; y donde un grupo arilo está presente en R⁵ está sustituido opcionalmente de modo independiente con uno o más sustituyentes seleccionados de alquilo C₁₋₁₀, tal como -alquilo C₁₋₄, halo, -CN, -NO₂, -CF₃, -NR¹⁰C(O)R¹⁰, -OCF₃, -CON(R¹⁰)₂, -COOR⁹, -OCOR¹⁰, -NR¹⁰COOR¹⁰, -OCON(R¹⁰)₂, -NR¹⁰CON(R¹⁰)₂, -OR⁹, -SR⁹, -NR¹⁰SO₂R¹⁰, -SO₂N(R¹⁰)₂ y -SO₂R¹⁰ donde cada R⁹ es de modo independiente alquilo C₁₋₁₀, tal como -alquilo C₁₋₄ y cada R¹⁰ es de modo independiente H o alquilo C₁₋₁₀, tal como -alquilo C₁₋₄; y opcionalmente donde un grupo alquilo, cicloalquilo o heterociclilo está presente en R⁵ que está sustituido opcionalmente de modo independiente con uno o más sustituyentes seleccionados de alquilo C₁₋₁₀,tal como -alquilo C₁₋₄, halo, -CN, -NO₂, -CF₃, -C(O)R¹⁰, -NR¹⁰C(O)R¹⁰, -OCF₃, -CON(R¹⁰)₂, -COOR⁹, -OCO0R¹⁰, -NR¹⁰COOR¹⁰, -OCON(R¹⁰)₂, -NR¹⁰CON(R¹⁰)₂, -OR⁹, -SR⁹, -NR¹⁰SO₂R¹⁰, -SO₂N(R¹⁰)₂ y -SO₂R¹⁰, donde cada R⁹ es de modo independiente alquilo C₁₋₁₀, tal como -alquilo C₁₋₄ y cada R¹⁰ es de modo independiente -H o alquilo C₁₋₁₀, tal como -alquilo C₁₋₄, excepto que alquilo no está sustituido con alquilo; R⁸ es metilo o hidrógeno; con la salvedad que X y R⁵ juntos no son un L-a-aminoácido, tal como Lys, Arg, Dap, Ser, Phe, Trp, Leu, Ala, ácido a,g-diaminobutírico (Dab) o ácido a,b-diaminopropiónico (Dap) opcionalmente junto con Dgp y Abu.Polymyxin derivatives for use in a combination treatment with a second active substance, such as rifampin, for example for the treatment of a microbial infection. Claim 1: A polymyxin compound for use in a method of treatment or prophylaxis, in combination with an active ingredient, wherein the active ingredient is selected from the group consisting of: rifampin, rifabutin, rifalacil, rifapentin and rifaximin; oxacillin, methicillin, ampicillin, cloxacillin, carbenicillin, piperacillin, tricarcillin, flucloxacillin and nafcillin; azithromycin, clarithromycin, erythromycin, telithromycin, cetromycin and solithromycin; aztreonam and BAL30072; meropenem, doripenem, imipenem, ertapenem, biapenem, tomopenem and panipenem; tigecycline, omadacycline, eravacycline, doxycycline and minocycline; ciprofloxacin, levofloxacin, moxifloxacin and delafloxacin; fusidic acid; novobiocin; teichoplanin, telavancin, dalbavancin and oritavancin, and salts and solvates thereof acceptable for pharmaceutical use; and the polymyxin compound is a compound of the formula (1) and salts and solvates thereof acceptable for pharmaceutical use, where: X is -C (O) -, -NHC (O) -, -OC (O) -, -CH₂- or -SO₂-; and R¹ together with the carbonyl and nitrogen a group of the carbon to which it is attached, is a phenylalanine, leucine or valine moiety; R² together with the carbonyl and nitrogen a group of the carbon to which it is attached, is a leucine, threonine, iso-leucine, phenylalanine, valine or nor-valine residue; R³ together with the carbonyl and nitrogen a group of the carbon to which it is attached, is a threonine or leucine moiety; R⁴ is C₁₋₆ alkyl substituted with a hydroxyl group or an amino group; A is a covalent bond or an amino acid, such as an a-amino acid; R⁵ is G-L²-L¹-, G is selected from: C₂₋₁₂ alkyl, C₅₋₁₂ aryl, C₃₋₁₀ cycloalkyl, L¹ is a covalent bond, C₁₋₁₂ alkylene or C₂₋₁₂ heteroalkylene, L² is a covalent bond or C₄₋₁₀ heterocyclylene, with the proviso that L¹ is not C₁₋₁₂ alkylene when G is C₂₋₁₂ alkyl, and G-L²-L¹ is substituted with: (i) one, two or three hydroxyl groups or (ii) one , two or three groups -NR⁶R⁷ or (iii) one or two groups -NR⁶R⁷ and one, two or three hydroxyl groups, with the proviso that (i), (ii) and (iii) are optional substituents when L¹ is a C₂ heteroalkylene ₋₁₂ containing nitrogen and / or L² is a heterocyclylene Cl containing nitrogen, or R⁵ is D-L¹, where D is heterocyclyl C₄₋₁₀ and L¹ is as defined above and D-L¹- is substituted with: ( i) one, two or three hydroxyl groups or (ii) one, two or three -NR⁶R⁷ groups or (iii) one or two -NR⁶R⁷ groups and one, two or three hi groups droxyl, with the proviso that (i), (ii) and (iii) are optional substituents when L¹ is a C₂₋₁₂ heteroalkylene containing nitrogen and / or D is a C₄₋₁₀ heterocyclyl containing nitrogen, each R⁶ is independently hydrogen or C₁₋₄ alkyl; each R⁷ is independently hydrogen or C₁₋₄ alkyl; or NR⁶R⁷ is a guanidine group; or when G is C₃₋₁₀ cycloalkyl or C₅₋₁₂ aryl, R⁶ and R⁷ together with the nitrogen atom of a C₄₋₁₀ heterocycle; and where an aryl group is present in R⁵ it is optionally independently substituted with one or more substituents selected from C₁₋₁₀ alkyl, such as -C₁₋₄ alkyl, halo, -CN, -NO₂, -CF₃, -NR¹⁰C (O ) R¹⁰, -OCF₃, -CON (R¹⁰) ₂, -COOR⁹, -OCOR¹⁰, -NR¹⁰COOR¹⁰, -OCON (R¹⁰) ₂, -NR¹⁰CON (R¹⁰) ₂, -OR⁹, -SR⁹, -NR¹⁰SO₂R¹⁰, -SO₂N (R¹⁰) ₂ and -SO₂R¹⁰ where each R⁹ is independently C alquilo alkyl, such as -C₁₋₄ alkyl and each R¹⁰ is independently H or C₁₋₁₀ alkyl, such as -C₁₋₄ alkyl; and optionally where an alkyl, cycloalkyl or heterocyclyl group is present in R⁵ which is optionally independently substituted with one or more substituents selected from C₁₋₁₀ alkyl, such as -C₁₋₄ alkyl, halo, -CN, -NO₂, - CF₃, -C (O) R¹⁰, -NR¹⁰C (O) R¹⁰, -OCF₃, -CON (R¹⁰) ₂, -COOR⁹, -OCO0R¹⁰, -NR¹⁰COOR¹⁰, -OCON (R¹⁰) ₂, -NR¹⁰CON (R¹⁰) ₂, - OR⁹, -SR⁹, -NR¹⁰SO₂R¹⁰, -SO₂N (R¹⁰) ₂ and -SO₂R¹⁰, where each R⁹ is independently C alquilo alkyl, such as -C₁₋₄ alkyl and each R¹⁰ is independently -H or C₁₋ alkyl ₁₀, such as -C₁₋₄ alkyl, except that alkyl is not substituted with alkyl; R⁸ is methyl or hydrogen; with the proviso that X and R⁵ together are not a La-amino acid, such as Lys, Arg, Dap, Ser, Phe, Trp, Leu, Ala, a, g-diaminobutyric acid (Dab) or a, b-diaminopropionic acid ( Dap) optionally together with Dgp and Abu.

ARP140102014A 2013-05-22 2014-05-21 POLYMIXIN DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS AR096370A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB201309248A GB201309248D0 (en) 2013-05-22 2013-05-22 Compounds and combinations

Publications (1)

Publication Number Publication Date
AR096370A1 true AR096370A1 (en) 2015-12-23

Family

ID=48747182

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP140102014A AR096370A1 (en) 2013-05-22 2014-05-21 POLYMIXIN DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS

Country Status (2)

Country Link
AR (1) AR096370A1 (en)
GB (1) GB201309248D0 (en)

Also Published As

Publication number Publication date
GB201309248D0 (en) 2013-07-03

Similar Documents

Publication Publication Date Title
HRP20220898T1 (en) Polymyxin derivatives and their use in combination therapy together with different antibiotics
CO2022017049A2 (en) 2-amino-3-cyanothiophenes annulled and derived for the treatment of cancer
ECSP20040257A (en) NEW PYRIDOPYRIMIDINONES SUBSTITUTED WITH BENZYLAMINE AND DERIVATIVES AS INHIBITORS OF SOS1
TN2019000039A1 (en) Pyridopyrimdinone cdk2/4/6 inhibitors
BR112018010962A2 (en) compound, trifluoroacetic acid salt, pharmaceutical composition, method for treating a bacterial infection, and, use of a compound.
BR112015022787A2 (en) compounds, pharmaceutical compositions, kit or packaged pharmaceutical article, and method of treating a carm1-mediated disorder
RU2016139978A (en) POLYMYXIN DERIVATIVES AND THEIR APPLICATION IN COMBINED THERAPY IN TOGETHER WITH VARIOUS ANTIBIOTICS
BR112019023290A2 (en) THENOPYRIDINES AND BENZOTIOPHENES USEFUL AS INHIBITORS OF IRAK4
BR112016029846A2 (en) compound, pharmaceutical composition, methods for the method of treating a human, for inhibiting the activity of a phosphatidylinositol 3-kinase polypeptide and over inhibiting or destructive immune reactions or cancer cell growth or proliferation, kit, and, use of a compound, a pharmaceutically acceptable salt, isomer, or a mixture thereof?
BR112013003101A2 (en) hepatitis c virus inhibitors
BR112012008849A2 (en) compound, pharmaceutical composition, and use of a compound
BR112012029405A8 (en) macrocyclic compounds as trk kinase inhibitors
AR084935A1 (en) DERIVATIVES OF TYPE AZAINDAZOL OR DIAZAINDAZOL AS MEDICINES
AR090439A1 (en) SHORT ANTIMICROBIAL LIPOPEPTIDES
BR112013011580A2 (en) amino substituted bisphenyl pentanoic acid derivatives as nep inhibitors
AR076645A1 (en) RESORCINOL ISOXAZOLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM, SYNTHESIS PROCESS, SYNTHESIS INTERMEDIARIES AND USE OF THE SAME IN NEURODEGENERATIVE DISORDERS AND AS ANTITUMORAL AGENTS.
BR112015001502A2 (en) azaindazole or diazaindazole derivatives for pain management
AR093261A1 (en) 2-REPLACED CEFEM COMPOUNDS
AR092307A1 (en) MANOSE DERIVATIVES FOR THE TREATMENT OF BACTERIAL INFECTIONS
AR114309A1 (en) ANTIBACTERIAL COMPOUNDS, COMPOSITIONS OF THE SAME, AND METHODS USING THEM
BR112022000251A2 (en) Macrocyclic Spirocycle Derivatives as mcl-1 Inhibitors
MX2020003495A (en) Boronic acid derivatives and synthesis thereof.
BR112023000212A2 (en) MACROCYCLIC ETHER CONTAINING INDOL DERIVATIVES AS MCL-1 INHIBITORS
BR112016005317A2 (en) quinazoline derivatives and their use as DNA methyltransferase inhibitors
BR112019024549A2 (en) glycopeptide-derived compounds and uses thereof