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US 2017/0247409 A1Published application
Abietane-type diterpenoids
AssigneeUniversity of Helsinki
InventorsVãnia M. MOREIRA, Adyary FALLARERO, Jari YLI-KAUHALUOMA, Pia VUORELA, Mikko VAHERMO
Life of this patent
Estimating the term…
Abstract
The present invention relates to the field of wood rosin and resin acid derivatives and more particularly to abietane-type diterpenoids as well as different uses thereof. Furthermore, the present invention relates to methods of coating surfaces, preventing, reducing or inhibiting bacterial biofilm formation, and treating or preventing disorders caused by microbial growth and viability as well as bacterial colonization.
Claims36
A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in treatment or prevention of bacterial biofilms and/or other microbial infections
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl.
12 more elements
A compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-8-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-8-alkyl;
- or a pharmaceutically acceptable salt thereof;
- provided that when X is CH2, R2 is OH, and R3 is H, R1 is not H, iso-propyl or benzyl, or when X is CH2, R2 is OH, R3 is H, and R1 is in D-configuration, R1 is not isobutyl, p-OH substituted benzyl, indolyl or methyl-S-propanyl.
14 more elements
A compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl;
- or a pharmaceutically acceptable salt thereof;
- provided that
- when X is CH2, R2 is OH, and R3 is H, R1 is not H, Me, L—CH(CH3)2, CH2OH, L'CH2Ph, L-indolyl, L—(CH2)COOH;
- L—(CH2)2COOH;
- (CH2)2SMe;
- or
- when X is CH2, R2 is OMe, and R3 is H, R1 is not H, L—Me, L—CH2COOMe, L—CH(CH3)CH2CH3, L—CH2CH(CH3)2, CH2Ph, L—CH2OH, L—CH2(C6H4)-p-OH or L—CH(CH3)2.
19 more elements
A compound of formula (I),
- wherein
- X is selected from CH2 and C═O;
- R1 is CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl;
- or a pharmaceutically acceptable salt thereof,
- for use in treatment or prevention of a disease or a condition involving or resulting from bacterial biofilms and/or other microbial infections or treatment or prevention of disorders caused by microbial growth and viability as well as bacterial colonization in a subject.
11 more elements
The compound for use according to any one of claims 1, and 4 to 12, or the compound according to any one of claims 2, 3 and 10 to 13, wherein R2 is OH or OR′.
The method of claim 17, wherein in the composition further comprises at least one other agents selected from the group consisting of solvent, diluent, carrier, buffer, excipient, adjuvant, antiseptic, and a filling, stabilizing, thickening, wetting, dispersing, solubilizing, suspending, emulsifying, binding, disintegrating, encapsulating, coating, embedding, lubricating, colouring, flavouring agent, absorbent, absorption enhancer, humectant, and preservative.
Use of a compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-8-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-8-alkyl.
- for coating a surface of a material.
13 more elements
A coating comprising a compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and
- wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl.
13 more elements
A surface coated material, wherein the coating comprises the compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl.
12 more elements
A method of preventing, reducing or inhibiting bacterial biofilm or microbial formation, wherein said method comprises applying a composition comprising the compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl,
- into a material or to a surface of a material.
13 more elements
Use of the compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-8-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-8-alkyl.
- for preventing, reducing or inhibiting bacterial biofilm or microbial formation in or on a material.
13 more elements
Use of the compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-8-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-8-alkyl.
- in medical devices, water filtration systems, ship hulls, textiles, furniture, food and food-related related surfaces, pharmaceuticals and devices for drug delivery, dressings, coatings, laboratory devices, biosensors, materials for patterned cell culture, diagnostic kits, cleaning solutions or desinfectants.
13 more elements
A method of treating or preventing disorders caused by microbial growth and viability as well as bacterial colonization in a subject, wherein said method comprises administering an effective amount of a composition comprising a compound of formula (I)
- wherein
- X is selected from CH2, C═O and C═N—OH;
- each R1 is independently selected from a group consisting of H;
- optionally substituted unbranched or branched, cyclic or acyclic C1-8-alkyl, wherein the carbon chain is optionally interrupted once with NH, O or S;
- and CH2—Cy, wherein Cy is C3-8-cycloalkyl or a mono or bicyclic heterocyclyl or (hetero)aryl, optionally comprising 1 to 3 heteroatoms each independently selected from S, N and O, any of which may be optionally substituted one or more times;
- and wherein said optional substituents of R1 are each independently selected from the group consisting of halogen, C1-3-alkyl, C1-3-(per)haloalkyl, OR, SR, CN, NO2, NHC(NH2)2, COR, COOR, CONHR, NR2, NHCSR, NHCOR, NHCONHR, NHCOOR, OCOR, and OCONHR;
- and
- R2 is OH, OR′ or an amino acid residue of formula —Y1 or a dipeptide residue of formula —Y1Y2 or a C1-6-alkyl ester of said amino acid or said dipeptide residue;
- and
- R3 is H, OOH, COOR′, or OH;
- wherein
- Y1 and Y2 are each independently selected from natural and non-natural amino acids comprising in its side chain 0 to 15 carbon atoms and optionally 1 to 4 heteroatoms;
- R is H or C1-3-alkyl;
- and
- R′ is C1-6-alkyl,
- to the subject in need thereof.
13 more elements
The compound for use, use or method according to any one of the previous claims, wherein growth, viability or colonization of bacteria is inhibited or reduced.
The compound for use, use or method according to any one of the previous claims, wherein said bacteria are Gram-positive bacteria, Gram-negative bacteria, planktonic bacteria, bacteria growing in a biofilm or any combination thereof.
The compound for use, use or method according to any one of the previous claims, wherein said disorder caused by bacteria is selected from the group consisting of bacterial infections, inflammation caused by bacteria, bacterial tissue damage, impetigo, lung pneumonia of cystic fibrosis patients, otitis media, chronic wounds, Legionnaire's disease, nosocomial infections and hospital-acquired infections.
The compound for use, use or method according to any one of the previous claims, wherein a molar concentration of the compound of formula (I) is about 0.5-1000 μM.
The method according to any one of the previous claims, wherein the composition is applied or administered once or several times.
The method according to any one of the previous claims, wherein the composition is applied or administered before, after or concurrently with another antimicrobial agent.
Dependencies are inferred from the claim text.