Propenamide derivatives, polymers, copolymers and use thereof

Claim 2

A polymer of the propenamide derivative as defined in claim 1 or salts thereof.

Claim 3

The polymer of claim 2, wherein a molecular weight is in the range of from about 3,000 to 200,000.

Claim 4

A crosslinked polymer of the propenamide derivative as defined in claim 1 or salts thereof, which is obtained by copolymerizing the propenamide derivative with a polyfunctional monomer.

Claim 5

The crosslinked polymer or salts thereof of claim 4, wherein the unit derived from the polyfunctional monomer is contained in an amount of from 0.1 to 30 mol %.

Claim 6

A copolymer of a propenamide derivative of the general formula (I) having, as an essential structural unit, an adhesive peptide represented by the general formula (II) in the side chain with an anionic monomer represented by the following general formula (III) or salts thereof: Formula (I):    R¹R²C=CR³-CO-[NH]- Formula (II):    -[R¹]-[CO]-([X]-Arg-Gly-Asp-[Y]) n -[Z]-[R⁵]- Formula (III): H₂C=CR⁶-[CO]-[W]-R⁷ wherein R¹ and R² each represents a hydrogen atom or a carboxyl group and R³ represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group, X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; Z represents -O- or -NH-; one of R⁴ and R⁵ represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; R⁶ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms; W represents -O- or -NH-; R⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 11 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of carboxyl, sulfo and phosphoro groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent.

Claim 7

The copolymer of claim 6, wherein a molecular weight is in the range of from about 3,000 to 200,000.

Claim 8

The copolymer of claim 6, wherein the unit derived from the propenamide derivative is contained in an amount of from 0.1 to 90 mol %.

Claim 9

A crosslinked copolymer of the propenamide derivative as defined in claim 6 or salts thereof, which is obtained by copolymerizing the propenamide derivative and the anionic monomer with a polyfunctional monomer.

Claim 10

The crosslinked copolymer or salts thereof of claim 9, wherein the unit derived from the propenamide derivative is contained in an amount of from 0.1 to 90 mol % and the unit derived from the polyfunctional monomer is contained in an amount of from 0.1 to 30 mol %.

Claim 11

A copolymer of a propenamide derivative of the general formula (I) having, as an essential structural unit, an adhesive peptide represented by the general formula (II) in the side chain with a cationic monomer represented by the following general formula (IV) or salts thereof: Formula (I): R¹R²C=CR³-CO-[NH]- Formula (II):    -[R⁴]-[CO]-([X]-Arg-Gly-Asp-[Y]) n -[Z]-[R⁵]- Formula (IV):    H₂C=CR⁸-[CO]-[W]-R⁹ wherein R¹ and R² each represents a hydrogen atom or a carboxyl group and R³ represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group, X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; Z represents -O- or -NH-; one of R⁴ and R⁵ represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; R⁶ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms; W represents -O- or -NH-; R⁸ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms, wherein the alkyl group may be substituted with one or more of halogen atom, carbonyl, amino, hydroxyl, nitro and cyano groups; W represents -O- or -NH-; R⁹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 12 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of amino, imino, nitrilo, amidino, quaternary ammonium and ammonium groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent.

Claim 12

The copolymer of claim 11, wherein a molecular weight is in the range of from about 3,000 to 200,000.

Claim 13

The copolymer of claim 11, wherein the unit derived from the propenamide derivative is contained in an amount of from 0.1 to 90 mol %.

Claim 14

A crosslinked copolymer of the propenamide derivative as defined in claim 11 or salts thereof, which is obtained by copolymerizing the propenamide derivative and the cationic monomer with a polyfunctional monomer.

Claim 15

The crosslinked copolymer or salts thereof of claim 14, wherein the unit derived from the propenamide derivative is contained in an amount of from 0.1 to 90 mol % and the unit derived from the polyfunctional monomer is contained in an amount of from 0.1 to 30 mol %.

Claim 16

A composition for inhibiting adhesion of animal cells, which comprises as an effective component at least one member selected from the group consisting of: (1) a propenamide derivative of the following general formula (I) having, as an essential structural unit, an adhesive peptide represented by the following general formula (II) in the side chain or salts thereof: Formula (I):    R¹R²C=CR³-CO-[NH]- Formula (II):    -[R⁴]-[CO]-([X]-Arg-Gly-Asp-[Y]) n -[Z]-[R⁵]- wherein R¹ and R² each represents a hydrogen atom or a carboxyl group and R³ represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group, X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; Z represents -O- or -NH-; one of R⁴ and R⁵ represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; and [ ] means that each corresponding group or residue therebetween may be present or absent, (2) a copolymer of the propenamide derivative of the formula (I) with an anionic monomer represented by the following general formula (III) or salts thereof: Formula (III):    H₂C=CR⁶-[CO]-[W]-R⁷ wherein R⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 11 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of carboxyl, sulfo and phosphoro groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent, and (3) a copolymer of the propenamide derivative of the formula (I) with a cationic monomer represented by the following general formula (IV) or salts thereof: Formula (IV):    H₂C=CR⁸-[CO]-[W]-R⁹ wherein R⁸ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms, wherein the alkyl group may be substituted with one or more of halogen atom, carbonyl, amino, hydroxyl, nitro and cyano groups; W represents -O- or -NH-; R⁹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 12 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of amino, imino, nitrilo, amidino, quaternary ammonium and ammonium groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent.

Claim 17

A composition for inhibiting coagulation and/or adhesion of blood platelets, which comprises as an effective component at least one member selected from the group consisting of: (1) a propenamide derivative of the following general formula (I) having, as an essential structural unit, an adhesive peptide represented by the following general formula (II) in the side chain or salts thereof: Formula (I):    R¹R²C=CR³-CO-[NH]- Formula (II):    -[R⁴]-[CO]-([X]-Arg-Gly-Asp-[Y]) n -[Z]-[R⁵]- wherein R¹ and R² each represents a hydrogen atom or a carboxyl group and R³ represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group, X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; Z represents -O- or -NH-; one of R⁴ and R⁵ represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; and [ ] means that each corresponding group or residue therebetween may be present or absent, (2) a copolymer of the propenamide derivative of the formula (I) with an anionic monomer represented by the following general formula (III) or salts thereof: Formula (III):    H₂C=CR⁶-[CO]-[W]-R⁷ wherein R⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 11 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of carboxyl, sulfo and phosphoro groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent, and (3) a copolymer of the propenamide derivative of the formula (I) with a cationic monomer represented by the following general formula (IV) or salts thereof: Formula (IV):    H₂C=CR⁸-[CO]-[W]-R⁹ wherein R⁸ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms, wherein the alkyl group may be substituted with one or more of halogen atom, carbonyl, amino, hydroxyl, nitro and cyano groups; W represents -O- or -NH-; R⁹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 12 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of amino, imino, nitrilo, amidino, quaternary ammonium and ammonium groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent.

Claim 18

A substrate for cultivating animal cells, which comprises as an effective component at least one member selected from the group consisting of: (1) a crosslinked polymer of a propenamide derivative of the formula (I) having, as an essential structural unit, an adhesive peptide represented by the following general formula (II) in the side chain or salts thereof, which is obtained by copolymerizing the propenamide derivative with a polyfunctional monomer: Formula (I):    R¹R²C=CR³-CO-[NH]- Formula (II):    -[R⁴]-[CO]-([X]-Arg-Gly-Asp-[Y]) n -[Z]-[R⁵]- wherein R¹ and R² each represents a hydrogen atom or a carboxyl group and R³ represents a hydrogen or halogen atom, methyl, ethyl or carboxymethyl group, X and Y each represents an amino acid residue selected from the group consisting of Ser, Gly, Val, Asn and Pro or a peptide residue consisting of two or more of the amino acids; Z represents -O- or -NH-; one of R⁴ and R⁵ represents a hydrogen atom, and the other represents a linear or branched alkylene group having 1 to 11 carbon atoms or an arylene group having 6 to 11 carbon atoms wherein the alkylene and arylene groups may be substituted with one or more halogen atom, carbonyl, carboxyl, amino, hydroxyl, sulfo, aryl, nitro or cyano group, or unsaturated double or triple bond; n is an integer of from 1 to 5; and [ ] means that each corresponding group or residue therebetween may be present or absent; (2) a crosslinked copolymer of the propenamide derivative of the formula (I) or salts thereof, which is obtained by copolymerizing the propenamide derivative and an anionic monomer represented by the following general formula (III) or salts thereof with a polyfunctional monomer: Formula (III):    H₂C=CR⁶-[CO]-[W]-R⁷ wherein R⁷ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 11 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of carboxyl, sulfo and phosphoro groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent; and (3) a crosslinked copolymer of the propenamide derivative of the formula (I) or salts thereof, which is obtained by copolymerizing the propenamide derivative and a cationic monomer represented by the following general formula (IV) or salts thereof with a polyfunctional monomer: Formula (IV):    H₂C=CR⁸-[CO]-[W]-R⁹ wherein R⁸ represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 3 carbon atoms, wherein the alkyl group may be substituted with one or more of halogen atom, carbonyl, amino, hydroxyl, nitro and cyano groups; W represents -O- or -NH-; R⁹ represents a hydrogen atom or a linear or branched alkyl group having 1 to 12 carbon atoms or an aryl group having 6 to 12 carbon atoms wherein the alkyl and the aryl groups have at least one memeber selected from the group consisiting of amino, imino, nitrilo, amidino, quaternary ammonium and ammonium groups and may have further substituent, and [ ] means that each corresponding group or residue therebetween may be present or absent.

Claim 19

The substrate of claim 18, wherein the crosslinked polymer or the crosslinked copolymer is in the form of a hydrogel in an aqueous solution.