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US 7,608,244 B2Granted
Hydrophilic light absorbing compositions for determination of physiological function in critically ill patients
AssigneeMallinckrodt Inc.
InventorsSamuel Achilefu, Raghavan Rajagopalan, Richard B. Dorshow, Joseph E. Bugaj, Muthunadar P. Periasamy
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Abstract
Highly hydrophilic indole and benzoindole derivatives that absorb and fluoresce in the visible region of light are disclosed. These compounds are useful for physiological and organ function monitoring. Particularly, the molecules of the invention are useful for optical diagnosis of renal and cardiac diseases and for estimation of blood volume in vivo.
Claims20
A compound of Formula 2
- wherein
- W2 is selected from the group consisting of O, Se, NRc, and S;
- Y2 is selected from the group consisting of C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, saccharides, C1-C10 aminoalkyl, hydrophilic peptides, arylpolysulfonates, C1-C10 aryl, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNHPO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHCSNH(CH2)bPO3HT, —(CH2)aNHCSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)c—CH2—OH, —(CH2)d—CO2T, —CH2—(CH2—O—CH2)e—CH2—CO2T, —(CH2)f—NH2, —CH2—(CH2—O—CH2)g—CH2—NH2, —(CH2)h—N(Ra)—(CH2)i—CO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- R8 is C1-C10 alkyl;
- —H or C1-C10 aryl
- R9, R10, R11, R12, R13 and R14 are independently selected from the group consisting of H, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, saccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, hydrophilic peptides, arylpolysulfonates, C1-C10 alkyl, C1-C10 aryl, —SO3T, —CO2T, —OH, —(CH2)aSO3T, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNHPO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHCSNH(CH2)bPO3HT, —(CH2)aNHCSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)c—CH2—OH, —(CH2)d—CO2T, —CH2—(CH2—O—CH2)e—CH2—CO2T, —(CH2)f—NH2, —CH2—(CH2—O—CH2)g—CH2—NH2, —(CH2)h—N(Ra)—(CH2)i—CO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- a, b, d, f, h, i, and j independently vary from 1-10 with the proviso that when a=2 and b=2, Y2 is not —(CH2)aCONH(CH2)bSO3T;
- c, e, g, and k independently vary from 1-100;
- Ra, Rb, Rc, and Rd are defined in the same manner as Y2;
- and
- T is either H or a negative charge.
8 more elements
A pharmaceutical composition comprising an effective amount of a compound of Formula 2
- wherein
- W2 is selected from the group consisting of O, Se, NRc, and S;
- Y2 is independently selected from the group consisting of C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, saccharides, C1-C10 aminoalkyl, hydrophilic peptides, arylpolysulfonates, C1-C10 aryl, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNHPO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHCSNH(CH2)bPO3HT, —(CH2)aNHCSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)C—CH2—OH, —(CH2)d—CO2T, —CH2—(CH2—O—CH2)e—CH2—CO2T, —(CH2)fNH2, —CH2—(CH2—O—CH2)gCH2NH2, —(CH2)hN(Ra)—(CH2)iCO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- R8 is C1-C10 alkyl;
- R9, R10, R11, R12, R13 and R14 are independently selected from the group consisting of H, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, saccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, hydrophilic peptides, arylpolysulfonates, C1-C10 alkyl, C1-C10 aryl, —SO3T, —CO2T, —OH, —(CH2)aSO3T, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNH PO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHOSNH(CH2)bPO3HT, —(CH2)aNHOSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)C—CH2—OH, —(CH2)dCO2T, —CH2(CH2—O—CH2)e—CH2—CO2T, —(CH2)f—NH2, —CH2—(CH2—O—CH2)g—CH2NH2,(CH2)h—N(Ra)—(CH2)i—CO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- a, b, d, f, h, i, and j independently vary from 1-10 with the proviso that when a=2 and b=2, Y2 is not —(CH2)aCONH(CH2)bSO3T;
- c, e, g, and k independently vary from 1-100;
- Ra, Rb, Rc, and Rd are defined in the same manner as Y2;
- and
- T is either H or a negative charge.
7 more elements
A method for performing a diagnostic or therapeutic procedure comprising administering to a mammal an effective amount of a compound of formula 2
- wherein
- W2 is selected from the group consisting of O, Se, and NRc;
- Y2 is independently selected from the group consisting of C1-C10alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20polyhyd roxyalkyl, C5-C20 polyhydroxyaryl, saccharides, C1C10 aminoalkyl, hydrophilic peptides, arylpolysulfonates, C1-C10 aryl, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNHPO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHCSNH(CH2)bPO3HT, —(CH2)aNHCSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)C—CH2—OH, —(CH2)d—CO2T, —CH2—(CH2—(CH2—O—CH2)e—CH2CO2T, —(CH2)fNH2,—CH2—(CH2—O—CH2)gCH2NH2,(CH2)h—N(Ra)(CH2)iCO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- R8 is C1-C10 alkyl;
- R9 R10 R11 R12 R13 and R14 are independently selected from the group consisting of H, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, saccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, hydrophilic peptides, arylpolysulfonates, C1-C10alkyl, C1-C10 aryl, —SO3T, —CO2T, —OH, —(CH2)aSO3T, —(CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)aCO2(CH2)bSO3T, —(CH2)aOCO(CH2)bSO3T, —(CH2)aCONH(CH2)bSO3T, —(CH2)aNHCO(CH2)bSO3T, —(CH2)aNHCONH(CH2)bSO3T, —(CH2)aNHCSNH(CH2)bSO3T, —(CH2)aOCONH(CH2)bSO3T, —(CH2)aPO3HT, —(CH2)aPO3T2, —(CH2)aOPO3HT, —(CH2)aOPO3T2, —(CH2)aNHPO3HT, —(CH2)aNHPO3T2, —(CH2)aCO2(CH2)bPO3HT, —(CH2)aCO2(CH2)bPO3T2, —(CH2)aOCO(CH2)bPO3HT, —(CH2)aOCO(CH2)bPO3T2, —(CH2)aCONH(CH2)bPO3HT, —(CH2)aCONH(CH2)bPO3T2, —(CH2)aNHCO(CH2)bPO3HT, —(CH2)aNHCO(CH2)bPO3T2, —(CH2)aNHCONH(CH2)bPO3HT, —(CH2)aNHCONH(CH2)bPO3T2, —(CH2)aNHCSNH(CH2)bPO3HT, —(CH2)aNHCSNH(CH2)bPO3T2, —(CH2)aOCONH(CH2)bPO3HT, —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—CH2)2OH, —(CH2)dCO2T, —CH2(CH2—O—CH2)e—CH2—CO2T, —(CH2)1—NH2, —CH2—(CH2—O—CH2)g—CH2—NH2, —(CH2)h—N(Ra)—(CH2)iCO2T, and —(CH2)j—N(Rb)—CH2—(CH2—O—CH2)k—CH2—CO2T;
- a, b, d, f, h, i, and j independently vary from 1-10 with the proviso that when a=b 2 and b=2,Y2 is not —(CH2)aCONH(CH2)bSO3T;
- c, e, g, and k independently vary from 1-100;
- Ra, Rb, Rc, and Rd are defined in the same manner as Y2;
- and
- T is either H or a negative charge, and thereafter performing the diagnostic or therapeutic procedure.
7 more elements
Dependencies are inferred from the claim text.