×

Non-fluorescent asymmetric cyanine dye compounds useful for quenching reporter dyes

  • US 6,348,596 B1
  • Filed: 07/20/1999
  • Issued: 02/19/2002
  • Est. Priority Date: 01/23/1998
  • Status: Expired due to Term
0
Associated Cases
0
Associated Defendants
0
Product Citations
0
Petitions
93
Forward Citations
12
Assignments
First Claim
Patent Images

1. A compound of formula (I):

  • embedded imagealone or in combination with a counterion thereof, wherein;

    p is 0 or 1;

    n is 0 or 1;

    X is S, Se or O;

    N1 is nitrogen;

    Z is selected from the group consisting of;

    embedded imageeither;

    (a) R2 is A, Y1 is H, and R1 is —

    L—

    Rx, or (b) R2 is —

    L—

    Rx, and;

    (i) R1 is A, or p3 (ii) p is 1, and R1 and Y1 taken together are (CH2)q;

    A is selected from the group consisting of alkyl, aryl, —

    CH2aryl, and —

    (CH2)mN+(CH3)3;

    L is selected from the group consisting of a bond, alkyldiyl, substituted alkyldiyl, alkyleno, substituted alkyleno, heteroalkyldiyl, substituted heteroalkyldiyl, heteroalkyleno, substituted heteroalkyleno, acyclic heteroatomic bridge, aryldiyl, substituted aryldiyl, arylaryldiyl, substituted arylaryldiyl, arylalkyldiyl, substituted arylalkyldiyl, heteroaryldiyl, substituted heteroaryldiyl, heteroaryl-heteroaryldiyl, substituted heteroaryl-heteroaryldiyl, heteroarylalkyldiyl, substituted heteroarylalkyldiyl, heteroaryl-heteroalkyldiyl, and substituted heteroaryl-heteroalkyldiyls;

    said heteroalkyldiyl being an alkyldiyl group containing one or more —

    O—

    , —

    O—

    O—

    , —

    S—

    , —

    S—

    S—

    , —

    O—

    S—

    , —

    O—

    NR′

    —

    , —

    NR′

    —

    , NR′

    —

    NR′

    —

    , ═

    N═

    N═

    , —

    N═

    N—

    , —

    N—

    O—

    N—

    , —

    NR′

    —

    N═

    N—

    , —

    PH—

    , —

    SH2—

    , or —

    S(O)2—

    groups, said R′

    being independently hydrogen or (C1-C6) alkyl;

    said heteroalkyleno being an alkyleno group containing one or more —

    O—

    , —

    O—

    O—

    , —

    S—

    , —

    S—

    S—

    , —

    O—

    S—

    , —

    O—

    NR′

    —

    , —

    NR′

    —

    , NR′

    —

    NR′

    —

    , ═

    N═

    N═

    , —

    N═

    N—

    , —

    N—

    O—

    N—

    , —

    NR′

    —

    N═

    N—

    , —

    PH—

    , —

    SH2—

    , or —

    S(O)2—

    groups, said R′

    being independently hydrogen or (C1-C6 ) alkyl;

    said acyclic heteroatomic bridge being selected from the group consisting of —

    O—

    , —

    O—

    O—

    , —

    S—

    , —

    S—

    S—

    , —

    O—

    S—

    , —

    O—

    NR′

    —

    , —

    NR′

    —

    , NR′

    —

    NR′

    —

    , ═

    N═

    N═

    , —

    N═

    N—

    , —

    N—

    O—

    N—

    , —

    NR′

    —

    N═

    N—

    , —

    PH—

    , —

    SH2—

    , and —

    S(O)2—

    , wherein R′

    is independently hydrogen or (C1-C6 alkyl);

    said heteroaryldiyl being a divalent radical derived from a compound selected from the group consisting of acridine, arsindole, carbazole, β

    -carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole and xanthene;

    said heteroaryl being a monovalent radical derived from a compound selected from the group consisting of acridine, arsindole, carbazole, β

    -carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole and xanthene;

    Rx is selected from the group consisting of acrylamide, acyl azide, acyl nitrile, acyl halide, aldehyde, alkyl halide, amine, anhydride, aniline, aryl halide, azide, aziridine, boronate, carboxylic acid, —

    COO−

    M+ wherein M+ is a counterion, diazoalkane, haloacetamide, halotriazine, hydrazine, —

    CO(oxysuccinimidyl), —

    CO(oxysulfosuccinimidyl), —

    CO(oxybenzotriazoyl), isocyanate, isothiocyanate, maleimide, phosphoramidite, sulfonyl halide, thiol, and azidoperfluorobenzamido;

    q is an integer ranging from 2 to 4;

    each m is independently an integer ranging from 2 to 12;

    A or (CH2)q is unsubstituted or independently substituted with one or more of the same or different —

    NO2, —

    OH, alkoxy, —

    COOH, —

    COOC1-C4 alkyl, —

    NHCHO, —

    NHCOC1-C4alkyl, —

    NHCOCH3, —

    NHCOCH2Cl, —

    NHCOCHCl2, —

    NHCOCCl3, —

    NHCOCF3, —

    NHCOCH2C6H4-o-NO2, —

    NHCOCH2OC6H4-o-NO2, —

    NHCOCH2COCH3, —

    NHCOCH2—

    N+C5H5Cl−

    , —

    NHCOCH2NHCS2CH2C6H5, —

    NHCOCH2CH2C6H5, —

    NHCOCH2CH2C6H4-p-OH, —

    NHCOCH2CH2C6H4—

    o—

    NO2, —

    NHCOC(CH3)2OC6H4-o-NO2, —

    NHCOC(CH3)2OC6H4-o-N═

    NC6H5, —

    NHCO(CH2)3Cl, —

    NHCOCH(CH3)2, —

    NHCOCH═

    CHC6H4-o-NO2, or —

    NHCO-2-pyridyl groups;

    either;

    (a) R3, R5 and R6 are H and R4 is —

    NO2;

    or (b) R3 and R4 taken together form a benzo group substituted with one or two —

    NO2 groups and R5 and R6 are hydrogen;

    or (c) R4 and R5 taken together form a benzo group substituted with one or two —

    NO2 groups and R3 and R6 are hydrogen;

    or (d) R5 and R6 taken together form a benzo group substituted with one or two —

    NO2 groups and R3 and R4 are hydrogen; and

    with the proviso that when R1 in the compounds of formula (I) has an sp3 hybridized carbon atom that is covalently attached to N1, then that carbon atom is methyl or, when substituted, primary, or to which is attached one or more hydroxyl, phenol, catechol, carbonyl, carboxyl, thiol or amino protecting groups.

View all claims
  • 12 Assignments
Timeline View
Assignment View
    ×
    ×