Luminescent metal complexes for monitoring renal function
View Patent ↗Some embodiments of the present invention may be said to be directed to metal complexes of Formula I, wherein at least one of X 1 , X 2 , X 3 , R 1 , R 2 , R 3 , R 4 and R 5 is what may be characterized as an antenna capable of providing (e.g., absorbing and/or emitting) an appropriate electromagnetic signal. Some embodiments of the present invention are directed to ligands corresponding to metal complexes of Formula I. Some embodiments of the invention are directed to methods of determining renal function using at least one metal complex of Formula I.
1. A compound of Formula II, wherein
X 1 , X 2 , and X 3 are independently selected from Ar 1 -Z 1 -, —O − , —NH(CH 2 ) a OH, —NH(CH 2 ) a CO 2 H, —NH(CH 2 ) a SO 3 − , —NH(CH 2 ) a OSO 3 − , —NH(CH 2 ) a NHSO 3 − , —O(CH 2 ) a SO 3 31 , —O(CH 2 ) a OSO 3 − , —O(CH 2 ) a NHSO 3 − , —NH(CH 2 ) a PO 3 H − , —NH(CH 2 ) a PO 3 ═ , —NH(CH 2 ) a OPO 3 H − , —NH(CH 2 ) a OPO 3 ═ , —NH(CH 2 ) a NHPO 3 H − , —NH(CH 2 ) a NHPO 3 ═ , —O(CH 2 ) a PO 3 H − , —O(CH 2 ) a PO 3 ═, —O(CH 2 ) a OPO 3 H − , —O(CH 2 ) a OPO 3 ═ , —O(CH 2 ) a NHPO 3 H − , and —O(CH 2 ) a NHPO 3 ═ ;
Y 1 and Y 2 are independently selected from a single bond, —(CH 2 ) m —, —(CH 2 ) m O—, —(CH 2 ) m OCO—, —(CH 2 ) m CO 2 —, —(CH 2 ) m OCNH—, —(CH 2 ) m OCO 2 —, —(CH 2 ) m NHCO—, —(CH 2 ) m NHCONH—, —(CH 2 ) m NHCSNH—, —(CH 2 ) m OSO 2 —, —(CH 2 ) m OSO 3 —, —(CH 2 ) m SO 2 ,—, —(CH 2 ) m NHSO 2 , — and —(CH 2 ) m SO 2 NH—;
Z 1 is —NH—, —O—, —NH(CH 2 ) m—, or —O(CH 2 ) m —;
Ar 1 is a bicyclic heteroaromatic radical having a base ring structure containing 5 to 10 carbon;
R1 to R5 are independently selected from Ar 2 -Z 2 -, hydrogen, C1-C10 alkyl, C1-C10 hydroxyalkyl, C1-C10 polyhydroxyalkyl, carboxyl, C1-C10 carboxyalkyl, C1-C10 alkoxyalkyl, —(CH 2 ) b SO 3 − , —(CH 2 ) b OSO 3 − , —(CH 2 ) b NHSO 3 − , —(CH 2 ) b CO 2 (CH 2 ) c SO 3 − , —(CH 2 ) b OCO(CH 2 ) c SO 3 − , —(CH 2 ) b CONH(CH 2 ) c SO 3 − , —(CH 2 ) b NHCO(CH 2 ) c SO 3 − , —(CH 2 ) b NHCONH(CH 2 ) c SO 3 − , —(CH 2 ) b NHCSNH(CH 2 ) c SO 3 − , —(CH 2 ) b OCONH(CH 2 ) c SO 3 − , —(CH 2 ) b PO 3 H − , —(CH 2 ) b PO 3 ═ , —(CH 2 ) b OPO 3 H −, —(CH 2 ) b OPO 3 ═ , —(CH 2 ) b NHPO 3 H − , —(CH 2 ) b NHPO 3 ═ , —(CH 2 ) b CO 2 (CH 2 ) c PO 3 H − , —(CH 2 ) b CO 2 (CH 2 ) c PO 3 ═ , —(CH 2 ) b OCO(CH 2 ) c PO 3 H − , —(CH 2 ) b OCO(CH 2 ) c PO 3 , —(CH 2 ) b CONH(CH 2 ) c PO 3 H − , (CH 2 ) b CONH(CH 2 ) c PO 3 ═ , —(CH 2 ) b NHCO(CH 2 ) c PO 3 H − , —(CH 2 ) b NHCO(CH 2 ) c PO 3 ═ , —(CH 2 ) b NHCONH(CH 2 ) c PO 3 H − , —(CH 2 ) b NHCONH(CH 2 ) c PO 3 ═ , —(CH 2 ) b NHCSNH(CH 2 ) c PO 3 H − , —(CH 2 ) b NHCSNH(CH 2 ) c PO 3 ═ , —(CH 2 ) b OCONH(CH 2 ) c PO 3 H − , or —(CH 2 ) b OCONH(CH 2 ) c PO 3 ═ ;
Z 2 is a single bond;
Ar 2 is a bicyclic heteroaromatic radical having a base ring structure containing 5 to 10;
a, b, and c independently are 1 to 6; and
m is 1 to 10;
with the proviso that at least one of X 1 to X 3 is Ar 1 -Z 1 - or at least one of R 1 to R 5 is Ar 2 -Z 2 -.
2. The compound of claim 1 , wherein X 1 is Ar 1 -Z 1 - and X 2 is —O − .
3. The compound of claim 1 , wherein each of X 1 and X 2 is Ar 1 -Z 1 -.
4. The compound of claim 2 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline.
5. The compound of claim 2 , wherein Z 1 - is —NH— or —NH(CH 2 ) m —.
6. The compound of claim 2 , wherein each of Y 1 and Y 2 is a single bond, X 3 is —O − , and each of R 1 -R 5 is hydrogen.
7. The compound of claim 2 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline; and Z 1 - is —NH— or —NH(CH 2 ) m —.
8. The compound of claim 2 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate or cyanoquinoxaline; each of Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 2 is hydrogen.
9. The compound of claim 2 , wherein Z 1 - is —NH— or —NH(CH 2 ) m —; each of Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 5 is hydrogen.
10. The compound of claim 2 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline; Z 1 - is —NH— or —NH(CH 2 ) m —; each of Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 5 is hydrogen.
11. The compound of claim 3 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline.
12. The compound of claim 3 , wherein Z 1 - is —NH— or —NH(CH 2 ) m —.
13. The compound of claim 3 , wherein each of Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 5 is hydrogen.
14. The compound of claim 3 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline; and Z 1 - is —NH— or —NH(CH 2 ) m —.
15. The compound of claim 3 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate or cyanoquinoxaline; each Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 5 is hydrogen.
16. The compound of claim 3 , wherein Z 1 - is —NH— or —NH(CH 2 ) m —; each Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of R 1 -R 5 is hydrogen.
17. The compound of claim 3 , wherein Ar 1 is quinoxaline, quinoxaline carboxylate, or cyanoquinoxaline; Z 1 - is —NH— or —NH(CH 2 ) m —; each of Y 1 and Y 2 is a single bond; X 3 is —O − ; and each of each R 1 -R 5 is hydrogen.