BIOORTHOGONAL COMPOSITIONS
The present disclosure provides bioorthogonal compositions for delivering agents in a subject. The disclosure also provides methods of producing the compositions, as well as methods of using the same.
1 - 55 . (canceled)
56 . A compound of formula (I),
or a pharmaceutically acceptable salt thereof,
wherein:
D is a chelated radionuclide;
L is a linker;
R 1 , at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, cycloalkenyl, —OR 1a , —NR 1b R 1c , —SR 1d , —SO 2 R 1e , —S(O)R 1f , and —P(O)OR 1g R 1h ;
R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g , and R 1h , are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl; and
n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl, at each occurrence, are independently substituted with 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substituents, each independently selected from the group consisting of halogen, ═O, ═S, cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, dialkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinylamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinyl, —COOH, ketone, amide, carbamate, silyl, substituted silyl, t-butyldimethylsilyl, alkylsulfanyl, sulfanyl, and acyl.
57 . The compound of claim 56 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 , at each occurrence, is independently selected from the group consisting of alkyl, heteroalkyl, and —OR 1a ;
R 1a is independently selected from the group consisting of hydrogen, alkyl, and heteroalkyl; and
n is 0, 1, 2, 3, or 4;
wherein said alkyl and heteroalkyl are independently substituted with 0, 1, or 2 substituents, each independently selected from the group consisting of ═O, —COOH, and hydroxy.
58 . The compound of claim 57 , or a pharmaceutically acceptable salt thereof, wherein R 1a is hydrogen.
59 . The compound of claim 57 , or a pharmaceutically acceptable salt thereof, wherein the compound has formula
and R 1 is alkyl.
60 . The compound of claim 59 , or a pharmaceutically acceptable salt thereof, wherein R 1 is unsubstituted alkyl.
61 . The compound of claim 58 , or a pharmaceutically acceptable salt thereof, wherein the compound is derived from
62 . The compound of claim 56 , or a pharmaceutically acceptable salt thereof, wherein the linker is a non-releasable linker.
63 . The compound of claim 56 , or a pharmaceutically acceptable salt thereof, wherein the linker includes one or more functional groups selected from the group consisting of ethylene-oxy, amine, ester, amide, carbamate, carbonate, and ketone functional groups.
64 . The compound of claim 63 , or a pharmaceutically acceptable salt thereof, wherein the linker comprises one or more ethylene-oxy and amide functional groups,
65 . The compound of claim 56 , or a pharmaceutically acceptable salt thereof, wherein the radionuclide is 90 Y, 111 In, or 177 Lu.
66 . The compound of claim 56 , or a pharmaceutically acceptable salt thereof, wherein the chelator of the radionuclide is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).