Nova Patents
EP2054476B9

Flourescent dyes for use in glucose sensing

Abstract

A novel class of compounds that includes HPTS-Cys-MA, and methods of making them are disclosed herein. The class of compounds including HPTS-Cys-MA are useful as fluorescent dyes for analyte detection.

EP2054476B9, drawing sheet 1
Sheet 1 of 151

Term

0.8 yearsleft in the term

Expires 24 July 2027.

  1. Priority
  2. Filed
  3. Granted
  4. Today
  5. Expires

13 claims: 2 independent, 11 dependent

  1. 1
    The compound:wherein: R 2 is R 3 is -(CH 2 ) n -A - M + , wherein n is 1-4, wherein A - is an anionic group selected from the group consisting of SO 3 - , HPO 3 - , CO 2 - and , and wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups;R 4 is R 5 is selected from the group consisting of and wherein n is equal to 1-10, n' is equal to 2-4 and Y is selected from the group consisting of NH and O;R 6 is selected from the group consisting of NHR 7 , OR 7 and CO 2 H;and R 7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
  2. 2
    The compound:wherein: R 3 is -(CH 2 ) n -A - M + , wherein n is 1-4, wherein A - is an anionic group selected from the group consisting of SO 3 - , HPO 3 - , CO 2 - and , and wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups;R 4 is R 8 is selected from the group consisting of and wherein n is equal to 1-10, n' is equal to 2-4;R 9 is selected from the group consisting of NHR 10 , OR 10 and CO 2 H;and R 10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
  3. 3
    The compound of Claim 2, wherein the compound is:
  4. 4
    The compound of Claim 3, wherein NBu 4 is any other counterion.
  5. 5
    The compound of Claim 3, comprising L, D, or L and D stereoisomers of cysteine.
  6. 6
    A glucose sensor comprising the compound of Claim 1.
  7. 7
    The glucose sensor of Claim 6, further comprising a quencher moiety.
  8. 8
    The glucose sensor of Claim 7, wherein said quencher moiety comprises boronic acid.
  9. 9
    The glucose sensor of Claim 8, wherein said boronic acid quencher is 3,3'-oBBV.
  10. 10
    A method of making the compound of Claim 1, comprising the steps of:wherein: R 2 is R 3 is -(CH 2 ) n -A - M + , wherein n is 1-4, wherein A - is an anionic group selected from the group consisting of SO 3 - , HPO 3 - , CO 2 - and , and wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups;R 4 is R 5 is selected from the group consisting of and wherein n is equal to 1-10, n' is equal to 2-4 and Y is selected from the group consisting of NH and O;R 6 is selected from the group consisting of NHR 7 , OR 7 and CO 2 H;R 7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido;and Z is an amino protecting group selected from the group consisting of Phthalimido, Boc and Fmoc.
  11. 11
    A method of making the compound of Claim 2, comprising the steps of:wherein: R 3 is -(CH 2 ) n -A - M + , wherein n is 1-4, wherein A - is an anionic group selected from the group consisting of SO 3 - , HPO 3 - , CO 2 - and , and wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups;R 8 is selected from the group consisting of and wherein n is equal to 1-10, n' is equal to 2-4;R 9 is selected from the group consisting of NHR 10 , OR 10 and CO 2 H;and R 10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
  12. 12
    A method of making the compound of Claim 3, comprising the steps of making HPTS-CysOH as follows; and making HPTS-Cys-MA as follows:
  13. 13
    A method of making the compound of Claim 3, comprising the steps of:making TBCys as follows: making Phth acid as follows: making Phth MA as follows: making AminoCysMA as follows: and making HPTS-Cys-MA as follows:
Independent claims13