US 12,303,570 B2
Compositions and methods for assessing eye vasculature
Richard B. Dorshow, Ballwin, MO (US); and Thomas E. Rogers, Ballwin, MO (US)
Assigned to MEDIBEACON INC., St. Louis, MO (US)
Filed by MediBeacon Inc., St. Louis, MO (US)
Filed on Oct. 1, 2021, as Appl. No. 17/492,260.
Application 16/694,982 is a division of application No. 15/572,706, granted, now 10,525,149, issued on Jan. 7, 2020, previously published as PCT/US2016/032167, filed on May 12, 2016.
Application 17/492,260 is a continuation of application No. 16/694,982, filed on Nov. 25, 2019, granted, now 11,160,880.
Claims priority of provisional application 62/160,338, filed on May 12, 2015.
Prior Publication US 2022/0016269 A1, Jan. 20, 2022
Prior Publication US 2023/0132384 A9, Apr. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 49/00 (2006.01); A61B 5/00 (2006.01); C07D 241/20 (2006.01); C07K 5/078 (2006.01); A61B 1/04 (2006.01); A61B 5/026 (2006.01)
CPC A61K 49/0021 (2013.01) [A61B 5/0071 (2013.01); C07D 241/20 (2013.01); C07K 5/06139 (2013.01); A61B 1/042 (2013.01); A61B 5/0082 (2013.01); A61B 5/0261 (2013.01)] 31 Claims
 
1. A method for assessing the eye vasculature in a subject in need thereof, comprising the steps of:
a. administering an effective amount of a compound of structural Formula I

OG Complex Work Unit Chemistry
or a salt thereof; wherein
X1 and X2 are independently chosen from —CO(AA), —CN, —CO2R1, —CONR2R3, —COR4, —NO2, —SOR35, —SO2R6, —SO2OR7 and —PO3R8R9; wherein at least one of X1 and X2 is —CO(AA);
Y1 and Y2 are independently chosen from —OR10, —SR11, —NR12R13, —N(R14)COR15, —CONH(PS); —P(R16)2, —P(OR17)2 and

OG Complex Work Unit Chemistry
each Z1 is independently chosen from a bond, —CR18R19—, —O—, —NR20—, —NCOR21—, —S—, —SO—, and —SO2—;
each R1 to R21 are independently chosen from hydrogen, C1-C10 alkyl, C1-C10 alkyl substituted with hydroxyl and carboxylic acid, C3-C6 polyhydroxylated alkyl, C5-C10 aryl, C5-C10 heteroaryl, C3-C5 heterocycloalkyl, C3-C5 heterocycloalkyl substituted with C(O), —(CH2)aCO2H, —(CH2)aCO2H substituted with C5-C10 heteroaryl, —(CH2)aCONR30R31, —(CH2)aNHSO3−, —(CH2)aNHSO3H, —(CH2)aOH, —(CH2)aOPO3−, —(CH2)aOPO3H2, —(CH2)aOPO3H−, (CH2)aOR22, —(CH2)aOSO3−, —(CH2)aOSO3H, —(CH2)aPO3−, —(CH2)aPO3H2, —(CH2)aPO3H−, —(CH2)aSO3−, —(CH2)aSO3H, —(CH2)dCO(CH2CH2O)cR23, —(CH2)d(CH2CH2O)cR24, —(CHCO2H)aCO2H, —CH2(CHNH2)aCH2NR25R26, —CH2(CHOH)aCO2H, —CH2(CHOH)aR27, —CH[(CH2)bNH2]aCH2OH, —CH[(CH2)bNH2]aCO2H, and —(CH2)aNR28R29;
each R22 to R31 are independently chosen from hydrogen, C1-C10 alkyl, and C1-C5-dicarboxylic acid;
R35 is chosen from C1-C10 alkyl, C1-C10 alkyl substituted with hydroxyl and carboxylic acid, C3-C6 polyhydroxylated alkyl, C5-C10 aryl, C5-C10 heteroaryl, C3-C5 heterocycloalkyl, C3-C5heterocycloalkyl substituted with C(O), —(CH2)aCO2H, —(CH2)aCO2H substituted with C5-C10 heteroaryl, —(CH2)aCONR30R31, —(CH2)aNHSO3−, —(CH2)aNHSO3H, —(CH2)aOH, —(CH2)aOPO3−, —(CH2)aOPO3H2, —(CH2)aOPO3H−, —(CH2)aOR21, —(CH2)aOSO3−, —(CH2)aOSO3H, —(CH)aPO3−, —(CH2)aPO3H2, —(CH2)aPO3H−, —(CH2)aSO3−, —(CH2)aSO3H, —(CH2)dCO(CH2CH2O)cR23, —(CH2)d(CH2CH2O)cR24, —(CHCO2H)nCO2H, —CH2(CHNH2)aCH2NR25R26, —CH2(CHOH)aCO2H, —CH2(CHOH)aR27, —CH[(CH2)bNH2]aCH2OH, —CH[(CH2)bNH2]aCO2H, and —(CH2)aNR28R29;
(AA) is a polypeptide chain comprising one or more natural or unnatural amino acids linked together by peptide bonds;
(PS) is a sulfated or non-sulfated polysaccharide chain comprising one or more monosaccharide units connected by glycosidic linkages; and
each ‘a’, ‘b’, and ‘d’ are independently chosen from 0 to 10, ‘c’ is chosen from 1 to 100 and each of ‘m’ and ‘n’ independently is an integer from 1 to 3; and
b. irradiating the subject's eye vasculature with non-ionizing radiation, wherein the radiation causes the compound to fluoresce;
c. detecting the fluorescence of the compound in the subject's eye vasculature; and
d. assessing the eye vasculature within the subject based on the detected fluorescence.