Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces

Claim 2

A compound of formula: in which X 1 is a reactive group that can react to form a covalent bond with a reactive group on the surface of a material to be rendered biocompatible, X2is a group -O⊖ or a precursor of such a group, n is 2, 3 or 4, Y is a group R 3 ⊖A wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A⊖is an anion present when X 2 is an electrically neutral group or Y is wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms.

Claim 3

A compound according to claim 1 wherein X 1 is (a) halogen, in which each R, which may be the same or different, represents a C 1 -C 4 alkyl group, preferably both methyl, and X 3 represents a group that will react with the reactive group on the surface to be rendered biocompatible with the formation of a covalent linkage, or where y is an integer of 1 to 10.

Claim 4

A compound according to claim 1 or claim 2 wherein X 1 or X 3 is chlorine.

Claim 5

A compound according to any one of claims 1 to 3 wherein Y is R 3 ⊖A and each R is methyl.

Claim 6

A compound according to any one of claims 1 to 4 wherein n is 2.

Claim 7

A compound according to any one of claims 1 to 3 wherein Y is

Claim 8

and n is 2.

Claim 9

and n is 2.

Claim 10

A compound according to claim 1 and selected from: choline acetate dichlorophosphate choline chlorodimethylsilylphosphate phosphalidyl choline ethylene glycol thallate phosphalidyl choline ethylene glycol dimethylsilyl- chloride phosphalidyl choline ethanolamine and 2-chloro-2-oxo-1,2,3-oxazapholane.

Claim 11

A mixture comprising at least one compound according to any preceding claim wherein Y is a group R 3 A and at least one compound according to any preceding claim wherein Y is

Claim 12

A mixture according to claim 8 comprising a compound of formula (I) wherein Y is a group R 3 .⊖A and a compound of formula (I) wherein Y is Ln a molar ratio of 19:1 to 4:1.

Claim 13

A process for producing a compound of formula I in which X 1 is a reactive group that can react to form a covalent bond with a reactive group on the surface of a material to be rendered biocompatible, X 2 is a group -0⊖ or a precursor of such a group, n is 2, 3 or 4, Y is a group R 3 A wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A⊖ is an anion present when X 2 is an electrically neutral group or Y is wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms comprising reacting a compound of formula: with a phosphorus oxyhalide or an analogue thereof.

Claim 14

A process for producing a compound of formula I in which X 1 is a reactive group that can react to form a covalent bond with a reactive group on the surface of a material to be rendered biocompatible, X 2 is a group -0⊖ or a precursor of such a group, n is 2, 3 or 4, Y is a group R 3 A wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A⊖ is an anion present when X 2 is an electrically neutral group or Y is wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms comprising reacting a compound of formula: with a phosphorus oxyhalide or an analogue thereof.

Claim 15

A process for producing a compound of formula wherein X 2 is a group -0⊖or a precursor of such a group, n is 2, 3 or 4, Y is a group R 3 wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A⊖ is an anion present when X2 is an electrically neutral group or Y is wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms and wherein x 1 is (a) halogen, in which each R, which may be the same or different, represents a C 1 -C 4 alkyl group, preferably both methyl, and x 3 represents a group that will react with the reactive group on the surface to be rendered biocompatible with the formation of a covalent linkage, or where y is an integer of 1 to 10 by reacting a compound of formula: with a silane of formula: to produce a compound of formula 1 wherein X 1 is or by reacting a compound of formula: with a compound to produce a compound of formula I where x 1 is or with a compound IIA as defined above to produce a compound of formula I wherein x 1 is or cleaving an oxazaphospholane of formula:

Claim 16

A process for producing a compound of formula wherein X 2 is a group -0⊖or a precursor of such a group, n is 2, 3 or 4, Y is a group R 3 wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A⊖ is an anion present when X2 is an electrically neutral group or Y is wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms and wherein x 1 is (a) halogen, in which each R, which may be the same or different, represents a C 1 -C 4 alkyl group, preferably both methyl, and x 3 represents a group that will react with the reactive group on the surface to be rendered biocompatible with the formation of a covalent linkage, or where y is an integer of 1 to 10 by reacting a compound of formula: with a silane of formula: to produce a compound of formula 1 wherein X 1 is or by reacting a compound of formula: with a compound to produce a compound of formula I where x 1 is or with a compound IIA as defined above to produce a compound of formula I wherein x 1 is or cleaving an oxazaphospholane of formula:

Claim 17

A process for rendering a surface biocompatible which comprises applying to the surrace a compound of formula I as defined in any one of claims to 7 or as produced by the process of claim 10 or claim 11 or a mixture as defined in claim 8 or claim 9 under conditions such that the group X 1 reacts to form a covalent linkage with a reactive group on the surface to be rendered biocompatible.

Claim 18

A process as claimed in claim 12 wherein the surface bearing the residue of a compound of formula I wherein Y is a group is treated with aqueous sodium bicarbonate.

Claim 19

A process as claimed in claim 13 wherein the surface bearing the residue of a compound of formula I wherein Y is a group is treated with dilute acetic acid.

Claim 20

An article to be introduced into the human or animal body or having a surface which is to be brought into contact with body fluids or cells or tissues which article has been treated with at least one compound of formula I as defined in any one of claims 1 to 7 or as produced by the process of claim 10 or claim 11 or with a mixture as defined by claim 8 or claim 9 or which has been treated by a process as defined in any one of claims 10 to 14.