Compositions of chelating molecules

Patent metadata

Field	Value
Publication number	US-12479792-B2
Application number	US-201716336665-A
Country	US
Kind code	B2
Filing date	Aug 28, 2017
Priority date	Sep 29, 2016
Publication date	Nov 25, 2025
Grant date	Nov 25, 2025

Abstract

Provided herein are a variety of metal chelators as well as methods of use thereof.

First claim

What is claimed is:

1 . A composition having a structure comprising:

wherein:
(i) A1, A2, A3, and A4, are independently selected from the group consisting of a CAM group, a 1,2-HOPO group, and an HA group, wherein at least one of A1, A2, A3, and A4 is a 1,2-HOPO group, at least one of A1, A2, A3, and A4 is a CAM group, and at least one of A1, A2, A3, and A4 is an HA group;
(ii) B1, B2, B3, and B4, are independently selected from the group consisting of an amide group and an amine group;
(iii) C1, C2, C3, C4, C5, and C6 are conjugation groups, wherein C1-C6 is independently selected from the group consisting of NH 2 , C(═O)OH, maleimide, dibromo-maleimide, isothiocyanate, alkyne, and azide;
(iv) at least another one of C1, C2, C3, C4, C5, or C6 is optional;
(v) L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are linking groups, wherein L1-L13 is independently selected from the group consisting of an alkyl group having 1 to 10 carbon atoms, an alkylamino group having 1 to 10 carbon atoms and 1 to 2 nitrogen atoms; an alkylamido group having 1 to 10 carbon atoms and 1 to 2 nitrogen atoms; an alkyl ether group having 1 to 10 carbon atoms, a hydroxy ester group, or an alkyl ester group having 1 to 10 carbon atoms; and
(vi) at least one of L1, L5, L6, L7, L8, L9, L10, L11, L12, or L13 is optional,
wherein the structure comprises a plurality of metal coordinating atoms, wherein the plurality of metal coordinating atoms is included in the 1,2-HOPO, CAM, and HA groups, wherein the metal coordinating atoms can bond with metals having cations with a +1, +2, +3, and/or +4 charge,
wherein the 1,2-HOPO group is defined by a structure

 and comprises a pyridinone ring substituted by a hydroxyl group on the N atom,
wherein the CAM group is defined by a structure

 and comprises at least a phenyl ring substituted by hydroxyl groups on adjacent carbon atoms,
wherein the HA group is defined by a structure

 wherein R α is H or an alkyl group including no greater than 5 carbon atoms, and
wherein the composition has at least one pharmaceutically acceptable carrier, wherein the at least one pharmaceutical acceptable carrier is selected from the group consisting of absorption delaying agents, antioxidants, binders, buffering agents, bulking agents or fillers, chelating agents, coatings, disintegration agents, dispersion media, gels, isotonic agents, lubricants, preservatives, pharmaceutically acceptable salts, solvents, stabilizers, and surfactants.

2 . A composition of claim 1 , wherein at least another one of L2, L3, or L4, is independently selected from the group consisting of an amine group or an amide group.

3 . A composition of claim 1 , wherein L1, C1, L7, C2, L9, C3, L11, C4, and L13, C5 are absent, L5 consists of an unsubstituted alkyl group having 1 to 5 carbon atoms, and C6 is selected from the group consisting of NH2, C(═O) OH, maleimide, dibromo-maleimide, isothiocyanate, alkyne, and azide.

4 . A composition of claim 3 , wherein L2, L3, L4, L6, L8, L10, and L12, independently, consist of an unsubstituted alkyl group having 1 to 5 carbon atoms.

5 . A composition of claim 4 , wherein A1 consists of a CAM group or a HOPO group; A2 consists of a HA group, A3 consists of a HA group, and A4 consists of a CAM group, a HOPO group, or a HA group.

6 . A composition of claim 1 , wherein at least one of L2, L3, or L4, independently, consists of an alkylamino or alkylamido group.

7 . A composition of claim 1 , wherein B1, B2, and B3, independently, consist of an amide group and B4 consists of an amino group, L2 and L3 consist of an amino group, and L4 consists of an alky group having 1 to 5 carbon atoms.

8 . A composition of claim 7 , wherein:
C1, C2, C3, C4, C5, L1, A1, A2, A3, L1, L6, L7, L8, L9, L10, L11, L12, and L13 are absent, A4 consists of a CAM group, a HOPO group, or a HA group; and L5 consists of an alkyl group having 1 to 5 carbon atoms.

9 . A composition of claim 1 , wherein B1, B2, and B3, independently, consist of an amide group and B4 consists of an amide group, L2 and L3, individually, consist of an amino group, and L4 consists of an alky group having 1 to 5 carbon atoms.

10 . A composition of claim 9 , wherein C1, C2, C3, C4, C5, A1, A2, A3, L1, L6, L7, L8, L9, L10, L11, and L13 are absent, L12 consists of an amino group, L5 consists of an ether group having 1 to 10 carbon atoms, and A4 consists of a CAM group, a HOPO group, or a HA group.

11 . A composition of claim 1 , wherein C1, C2, C5, C6, L1, L2, L3, L4, L5, L7, L13, B2, and B4 are absent, B1 and B3, independently, consist of an amide group, L6, L8, L10, and L12, independently, consist of an amino group, A1, A2, A3, and A4, independently, consist of a CAM group, a HOPO group, or a HA group, L9 and L11, independently, consist of an alkyl group having 1 to 5 carbon atoms.

12 . A composition of claim 1 , further comprising a metal, wherein the metal comprises a radionuclide.

13 . A composition of claim 12 , wherein the radionuclide comprises 225 Ac, 226 Ac, 228 Ac, 105 Ag, 106 mAg, 110 mAg, 111 Ag, 112 Ag, 113 Ag, 239 Am, 240 Am, 242 Am, 244 Am, 37 Ar, 71 As, 72 As, 73 As, 74 As, 76 As, 77 As, 209 At, 210 At, 191 Au, 192 Au, 193 Au, 194 Au, 195 Au, 196 Au, 196 m 2 Au, 198 Au, 198 mAu, 199 Au, 200 mAu, 128 Ba, 131 Ba, 133 mBa, 135 mBa, 140 Ba, 7 Be, 203 Bi, 204 Bi, 205 Bi, 206 Bi, 210 Bi, 212 Bi, 243 Bk, 244 Bk, 245 Bk, 246 Bk, 248 mBk, 250 Bk, 76 Br, 77 Br, 80 mBr, 82 Br, 11 C, 14 C, 45 Ca, 47 Ca, 107 Cd, 115 Cd, 115 mCd, 117 mCd, 132 Ce, 133 mCe, 134 Ce, 135 Ce, 137 Ce, 137 mCe, 139 Ce, 141 Ce, 143 Ce, 144 Ce, 246 Cf, 247 Cf, 253 Cf, 254 Cf, 240 Cm, 241 Cm, 242 Cm, 252 Cm, 55 Co, 56 Co, 57 Co, 58 Co, 58 mCo, 60 Co, 48 Cr, 51 Cr, 127 Cs, 129 Cs, 131 Cs, 132 Cs, 136 Cs, 137 Cs, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 153 Dy, 155 Dy, 157 Dy, 159 Dy, 165 Dy, 166 Dy, 160 Er, 161 Er, 165 Er, 169 Er, 171 Er, 172 Er, 250 Es, 251 Es, 253 Es, 254 Es, 254 mEs, 255 Es, 256 mEs, 145 Eu, 146 Eu, 147 Eu, 148 Eu, 149 Eu, 150 mEu, 152 mEu, 156 Eu, 157 Eu, 52 Fe, 59 Fe, 251 Fm, 252 Fm, 253 Fm, 254 Fm, 255 Fm, 257 Fm, 66 Ga, 67 Ga, 68 Ga, 72 Ga, 73 Ga, 146 Gd, 147 Gd, 149 Gd, 151 Gd, 153 Gd, 159 Gd, 68 Ge, 69 Ge, 71 Ge, 77 Ge, 170 Hf, 171 Hf, 173 Hf, 175 Hf, 179 m 2 Hf, 180 mHf, 181 Hf, 184 Hf, 192 Hg, 193 Hg, 193 mHg, 195 Hg, 195 mHg, 197 Hg, 197 mHg, 203 Hg, 160 mHo, 166 Ho, 167 Ho, 123 I, 124 I, 126 I, 130 I, 132 I, 133 I, 135 I, 109 In, 110 In, 111 In, 114 mIn, 115 mIn, 184 Ir, 185 Ir, 186 Ir, 187 Ir, 188 Ir, 189 Ir, 190 Ir, 190 m 2 Ir, 192 Ir, 193 mIr, 194 Ir, 194 m 2 Ir, 195 mIr, 42 K, 43 K, 76 Kr, 79 Kr, 81 mKr, 85 mKr, 132 La, 133 La, 135 La, 140 La, 141 La, 262 Lr, 169 Lu, 170 Lu, 171 Lu, 172 Lu, 174 mLu, 176 mLu, 177 Lu, 177 mLu, 179 Lu, 257 Md, 258 Md, 260 Md, 28 Mg, 52 Mn, 90 Mo, 93 mMo, 99 Mo, 13 N, 24 Na, 90 Nb, 91 mNb, 92 mNb, 95 Nb, 95 mNb, 96 Nb, 138 Nd, 139 mNd, 140 Nd, 147 Nd, 56 Ni, 57 Ni, 66 Ni, 234 Np, 236 mNp, 2

Assignees

• Univ California

Inventors

• Abergel Rebecca J
• Rees Julian
• Captain Ilya

Classifications

• C07K5/1008

  the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala · CPC title

• C07D213/89

  with hetero atoms directly attached to the ring nitrogen atom · CPC title

• A61K51/0482

  chelates from cyclic ligands, e.g. DOTA · CPC title

• A61K51/0478 Primary

  complexes from non-cyclic ligands, e.g. EDTA, MAG3 · CPC title

• A61K38/1709

  from mammals · CPC title