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US 6,887,854 B2Granted
Compounds as dynamic organ function monitoring agents
AssigneeMallinckrodt Inc.
InventorsSamuel Achilefu, Hermo N. Jimenez, Raghavan Rajagopalan, Richard B. Dorshow, Joseph E. Bugai
Life of this patent
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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.
Claims6
A compound having the formula
- wherein R16, R17, R18, R20, R21, R22 and R23, Y3, and Z3 are independently selected from the group consisting of —H, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, mono- and disaccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, arylpolysulfonates, C1-C10 alkyl, C5-C20 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, and —(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;
- R15 is selected from the group consisting of —(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, and —(CH2)aOCONH(CH2)bSO3T;
- R19 is selected from the group consisting of —H, C5-C10 alkoxyl, C5-C10 polyalkoxyalkyl, C7-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, mono- and disaccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, arylpolysulfonates, C7-C10 alkyl, C5-C20 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;
- W3 and X3 are selected from the group consisting of —CRcRd, —O—, —NRc, —S—, and —Se;
- V3 is a single bond or is selected from the group consisting of —O—, —S—, —Se—, and —NRa;
- a, b, d, f, h, i, and j are independently 1-10;
- c, e, g, and k are independently 1-100;
- a3 and b3 are independently 0 to 5;
- Ra, Rb, Rc, and Rd are defined in the same manner as Y3;
- and T is either H or a negative charge.
7 more elements
A composition comprising a pharmaceutically acceptable formulation of formula
- wherein R16, R17, R18, R20, R21, R22 and R23, Y3, and Z3 are independently selected from the group consisting of —H, C1-C10 alkoxyl, C1-C10 polyalkoxyalkyl, C1-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, mono- and disaccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, arylpolysulfonates, C1-C10 alkyl, C5-C20 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, and —(CH2)aOCONH(CH2)bPO3T2, —CH2(CH2—O—CH2)c—CH2—OH, —(CH2)d—CO2T, —CH2—(CH2—O—CH2)c—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;
- R15 is selected from the group consisting of —(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, and —(CH2)aOCONH(CH2)bSO3T;
- R19 is selected from the group consisting of —H, C5-C10 alkoxyl, C5-C10 polyalkoxyalkyl, C7-C20 polyhydroxyalkyl, C5-C20 polyhydroxyaryl, mono- and disaccharides, amino, C1-C10 aminoalkyl, cyano, nitro, halogen, arylpolysulfonates, C7-C10 alkyl, C5-C20 aryl, —SO3T, —CO2T, —OH, —(CH2)aSO3T, (CH2)aOSO3T, —(CH2)aNHSO3T, —(CH2)a—CO2(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;
- W3 and X3 are selected from the group consisting of —CRcRd, —O—, —NRc, —S—, and —Se;
- V3 is a single bond or is selected from the group consisting of —O—, —S—, —Se—, and —NRa;
- a, b, d, f, h, i, and j independently vary from 1-10;
- c, e, g, and k independently vary from 1-100;
- a3 and b3 vary from 0 to 5;
- Ra, Rb, Rc, and Rd are defined in the same manner as Y3;
- and T is either H or a negative charge, and pharmaceutically acceptable carrier or excipient.
7 more elements
Dependencies are inferred from the claim text.