Stabilization of radioiodinated and astatinated pharmaceuticals and imaging agents

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• X is selected from C—R2 and N;
• Y is selected from C—R3 and N;
• Z is selected from C—R4 and N,
• wherein at least one of X, Y, and Z is carbon;
• R1 is selected from radioactive iodine and radioactive astatine;
• R2 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR2a, —SR2a, —N(R2a)2, —N(R2a)C(O)R2b, —N(R2a)N(R2a)2, —NO2, —N(R2a)OR2a, —ON(R2a)2, —C(O)H, —C(O)R2b, —C(O)2R2a, —C(O)N(R2a)2, —C(O)N(R2a)(OR2a), —OC(O)N(R2a)2, —N(R2a)C(O)2R2a, —N(R2a)C(O)N(R2a)2, —OC(O)R2b, —S(O)R2b, —S(O)2R2b, —S(O)2N(R2a)2, —N(R2a)S(O)2R2b, —N(R2a)C(═N(R2a))N(R2a)2, —C(R2a)═N(R2a), and —C(R2a)═N(OR2a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R20;
• R2a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R20;
• R2b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R20;
• R3 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR3a, —SR3a, —N(R3a)2, —N(R3a)C(O)R3b, —N(R3a)N(R3a)2, —NO2, —N(R3a)OR3a, —ON(R3a)2, —C(O)H, —C(O)R3b, —C(O)2R3a, —C(O)N(R3a)2, —C(O)N(R3a)(OR3a), —OC(O)N(R3a)2, —N(R3a)C(O)2R3a, —N(R3a)C(O)N(R3a)2, —OC(O)R3b, —S(O)R3b, —S(O)2R3b, —S(O)2N(R3a)2, —N(R3a)S(O)2R3b, —N(R3a)C(═N(R3a))N(R3a)2, —C(R3a)═N(R3a), and —C(R3a)═N(OR3a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R30;
• R3a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R30;
• R3b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R30;
• R4 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR4a, —SR4a, —N(R4a)2, —N(R4a)C(O)R4b, —N(R4a)N(R4a)2, —NO2, —N(R4a)OR4a, —ON(R4a)2, —C(O)H, —C(O)R4b, —C(O)2R4a, —C(O)N(R4a)2, —C(O)N(R4a)(OR4a), —OC(O)N(R4a)2, —N(R4a)C(O)2R4a, —N(R4a)C(O)N(R4a)2, —OC(O)R4b, —S(O)R4b, —S(O)2R4b, —S(O)2N(R4a)2, —N(R4a)S(O)2R4b, —N(R4a)C(═N(R4a))N(R4a)2, —C(R4a)═N(R4a), and —C(R4a)═N(OR4a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R40;
• R4a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R40;
• R4b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R40;
• or wherein:
• i) R2 and R3;
• or ii) R3 and R4, together with the carbon atoms to which they are attached form a 4- to 7-membered carbocyclic or heterocyclic ring;
• R20 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR20a, —SR20a, —N(R20a)2, N(R20a)C(O)R20b, —N(R20a)N(R20a)2, —NO2, —N(R20a)OR20a, —ON(R20a)2, —C(O)H, —C(O)R20b, —C(O)2R20a, —C(O)N(R20a)2, —C(O)N(R20a)(OR20a), —OC(O)N(R20a)2, —N(R20a)C(O)2R20a, —N(R20a)C(O)N(R20a)2, —OC(O)R20b, —S(O)R20b, —S(O)2R20b, —S(O)2N(R20a)2, —N(R20a)S(O)2R20b, —N(R20a)C(═N(R20a))N(R20a)2, —C(R20a)═N(R20a), and —C(R20a)═N(OR20a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R20a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R20b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R30 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR30a, —SR30a, —N(R30a)2, —N(R30a)C(O)R30b, —N(R30a)N(R30a)2, —NO2, —N(R30a)OR30a, —ON(R30a)2, —C(O)H, —C(O)R30b, —C(O)2R30a, —C(O)N(R30a)2, —C(O)N(R30a)(OR30a), —OC(O)N(R30a)2, —N(R30a)C(O)2R30a, —N(R30a)C(O)N(R30a)2, —OC(O)R30b, —S(O)R30b, —S(O)2R30b, —S(O)2N(R30a)2, —N(R30a)S(O)2R30b, —N(R30a)C(═N(R30a))N(R30a)2, —C(R30a)═N(R30a), and —C(R30a)═N(OR30a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R30a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R30b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R40 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR40a, —SR40a, —N(R40a)2, —N(R40a)C(O)R40b, —N(R40a)N(R40a)2, —NO2, —N(R40a)OR40a, —ON(R40a)2, —C(O)H, —C(O)R40b, —C(O)2R40a, —C(O)N(R40a)2, —C(O)N(R40a)(OR40a), —OC(O)N(R40a)2, —N(R40a)C(O)2R40a, —N(R40a)C(O)N(R40a)2, —OC(O)R40b, —S(O)R40b, —S(O)2R40b, —S(O)2N(R40a)2, —N(R40a)S(O)2R40b, —N(R40a)C(═N(R40a))N(R40a)2, —C(R40a)═N(R40a), and —C(R40a)═N(OR40a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R40a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R40b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R90;
• R90 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR90a, SR90a, —N(R90a)2, —N(R90a)C(O)R90b, —N(R90a)N(R90a)2, —NO2, N(R90a)OR90a, —ON(R90a)2, —C(O)H, —C(O)R90b, —C(O)2R90a, —C(O)N(R90a)2, —C(O)N(R90a)(OR90a), —OC(O)N(R90a)2, —N(R90a)C(O)2R90a, N(R90a)C(O)N(R90a)2, —OC(O)R90b, —S(O)R90b, —S(O)2R90b, —S(O)2N(R90a)2, —N(R90a)S(O)2R90b, —N(R90a)C(═N(R90a))N(R90a)2, —C(R90a)═N(R90a), and —C(R90a)═N(OR90a);
• R90a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
• and
• R90b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl.

A compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein:
• Q is selected from O, S, and —N(R6)—;
• T is selected from C—R7 and N,
• wherein at least one of X, Y, and Z is carbon;
• R5 is selected from 123I, 131I, and 211At;
• R6 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR6a, —SR6a, —N(R6a)2, —N(R6a)C(O)R6b, —N(R6a)N(R6a)2, —NO2, —N(R6a)OR6a, —ON(R6a)2, —C(O)H, —C(O)R6b, —C(O)2R6a, —C(O)N(R6a)2, —C(O)N(R6a)(OR6a), —OC(O)N(R6a)2, —N(R6a)C(O)2R6a, —N(R6a)C(O)N(R6a)2, —OC(O)R6b, —S(O)R6b, —S(O)2R6b, —S(O)2N(R6a)2, —N(R6a)S(O)2R6b, —N(R6a)C(═N(R6a))N(R6a)2, —C(R6a)═N(R6a), and —C(R6a)═N(OR6a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R60;
• R6a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R60;
• R6b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R60;
• R7 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR7a, —SR7a, —N(R7a)2, —N(R7a)C(O)R7b, —N(R7a)N(R7a)2, —NO2, —N(R7a)OR7a, —ON(R7a)2, —C(O)H, —C(O)R7b, —C(O)2R7a, —C(O)N(R7a)2, —C(O)N(R7a)(OR7a), —OC(O)N(R7a)2, —N(R7a)C(O)2R7a, —N(R7a)C(O)N(R7a)2, —OC(O)R7b, —S(O)R7b, —S(O)2R7b, —S(O)2N(R7a)2, —N(R7a)S(O)2R7b, —N(R7a)C(═N(R7a))N(R7a)2, —C(R7a)═N(R7a), and —C(R7a)═N(OR7a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R70;
• R7a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R70;
• R7b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R70;
• or wherein:
• i) R6 and R7, together with the nitrogen and carbon atoms to which they are respectively attached can form a 4- to 7-membered heterocyclic ring;
• R60 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR60a, —SR60a, —N(R60a)2, —N(R60a)C(O)R60b, —N(R60a)N(R60a)2, —NO2, —N(R60a)OR60a, —ON(R60a)2, —C(O)H, —C(O)R60b, —C(O)2R60a, —C(O)N(R60a)2, —C(O)N(R60a)(OR60a), —OC(O)N(R60a)2, —N(R60a)C(O)2R60a, —N(R60a)C(O)N(R60a)2, —OC(O)R60a, —S(O)R60b, —S(O)2R60b, —S(O)2N(R60a)2, —N(R60a)S(O)2R60b, —N(R60a)C(═N(R60a))N(R60a)2, —C(R60a)═N(R60a), and —C(R60a)═N(OR60a), wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R60a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R60b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R70 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR70, —SR70a, —N(R70a)2, —N(R70a)C(O)R70b, —N(R70a)N(R70a)2, —NO2, —N(R70a)OR70a, —ON(R70a)2, —C(O)H, —C(O)R60b, —C(O)2R70a, —C(O)N(R70a)2, —C(O)N(R70a)(OR70a), —OC(O)N(R70a)2, —N(R70a)C(O)2R70a, —N(R60a)C(O)N(R70a)2, —OC(O)R70b, —S(O)R70b, —S(O)2R70b, —S(O)2N(R70a)2, —N(R70a)S(O)2R70b, —N(R70a)C(═N(R70a))N(R70a)2, —C(R70a)═N(R70a), and —C(R70a)═N(OR70a) wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R70a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R70b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein the C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R90;
• R90 is selected from H, halo, —CN, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, —OR90a, —SR90a, —N(R90a)2, —N(R90a)C(O)R90b, —N(R90a)N(R90a)2, —NO2, —N(R90a)OR90a, —ON(R90a)2, —C(O)H, —C(O)R90b, —C(O)2R90a, —C(O)N(R90a)2, —C(O)N(R90a)(OR90a), —OC(O)N(R90a)2, —N(R90a)C(O)2R90a, —N(R90a)C(O)N(R90a)2, —OC(O)R90b, —S(O)R90b, —S(O)2R90b, —S(O)2N(R90a)2, N(R90a)S(O)2R90b, —N(R90a)C(═N(R90a))N(R90a)2, —C(R90a)═N(R90a), and —C(R90a)═N(OR90a);
• R90a in each occurrence is independently selected from H, C1-6alkyl, carbocyclyl, and heterocyclyl;
• and
• R90b in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl.