08-03-2018 дата публикации
Номер: US20180064829A1
Fluorescent probes based on N-heterocyclic bisphosphonates or their phosphonocarboxylate analogues are provided. The probes have variable spectroscopic properties, bone mineral binding affinities, and pharmacological activities. Methods for preparing the probes include the use of two complementary linking strategies, one involving an amino group and the other involving a chloride group as a precursor to an amino group. In other versions, bifunctional N-heterocyclic bisphosphonates are provided having an amino group and an azido group as linking moieties. In some versions, the linking chemistry allows attachment of a wide selection of fluorescent dyes in the visible to near-infrared range to any of three clinically important heterocyclic bisphosphonates. 1. A toolkit for use in bone tissue , comprising a plurality of N-heterocyclic bisphosphonates , or phosphonocarboxylate analogues thereof , linked to imaging tags , wherein the imaging tag-linked N-heterocyclic bisphosphonates , or phosphonocarboxylate analogues thereof , exhibit preselected physical , optical and biological characteristics.2. The toolkit of claim 1 , comprising the imaging tag-linked N-heterocyclic bisphosphonates claim 1 , or the phosphonocarboxylate analogues thereof claim 1 , selected from the group consisting of 5 (6)-FAM-RIS (7a1) claim 1 , 5-FAM-RIS (7a2) claim 1 , 6-FAM-RIS (7a3) claim 1 , 5 (6)-RhR-RIS (7a4) claim 1 , 5 (6)-ROX-RIS (7a5) claim 1 , AF647-RIS (7a6) claim 1 , 5 (6)-FAM-RISPC (7b1) claim 1 , 5 (6)-RhR-RISPC (7b2) claim 1 , 5 (6)-ROX-RISPC (7b3) claim 1 , AF647-RISPC (7b4) claim 1 , 5 (6)-FAM-dRIS (7c1) claim 1 , 5 (6)-RhR-dRIS (7c2) claim 1 , 5-FAM-ZOL (7d1) claim 1 , 6-FAM-ZOL (7d2) claim 1 , AF647-ZOL (7d3) claim 1 , 800 CW-ZOL (7d4) claim 1 , Sulfo-Cy5-ZOL (7d5) claim 1 , 5-FAM-MIN (7e1) claim 1 , 6-FAM-MIN (7e2) claim 1 , 5-FAM-MINPC (7f1) claim 1 , and 6-FAM-MINPC (7f2) claim 1 , in Table 1.3. A method for analyzing bone claim 1 , bone metabolism claim 1 , bone interaction ...
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