Boronic acid adducts of technetium-99M dioxime complexes

Claim 2

A boronic acid adduct of technetium-99m dioxime complexes having the formula 99mTc X(Y) 3 Z, wherein X is an anion; Y is a vicinal dioxime having the formula or a pharmaceutically acceptable salt thereof, wherein R, and R 2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6- membered nitrogen or oxygen containing heterocycle, or together R, and R 2 are -(CR 8 R 9 ) n - wherein n is 3, 4, 5 or 6 and R 8 and Rg are each independently hydrogen or alkyl; and Z is a boron derivative of the formula . B-R 3 wherein R 3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl or - (R 4 R 5 N)-alkyl and R, and R s are each independently hydrogen, alkyl, or arylalkyl, or R 4 and R s when taken together with the nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle.

Claim 3

A boronic acid adduct in accordance with claim 1, wherein X is a halide.

Claim 4

A boronic acid adduct in accordance with claim 1, wherein X is chloride or bromide.

Claim 5

A boronic acid adduct in accordance with claim 1, wherein X is chloride.

Claim 6

A boronic acid adduct in accordance with claim 1, wherein Y is dimethyl glyoxime, 1,2-cyclohexanedione dioxime,1,2-ethanedione dioxime, a-furyldioxime, 1,2-cyclopentanedione dioxime, or 3-methyl-1,2-cyclopentanedione dioxime.

Claim 7

A boronic acid adduct in accordance with claim 1, wherein Y is dimethyl glyoxime.

Claim 8

A boronic acid adduct in accordance with claim 1, wherein Y is 1,2-cyclohexanedione dioxime.

Claim 9

A boronic acid adduct in accordance with claim 1, wherein Y is 1,2-ethanedione dioxime.

Claim 10

A boronic acid adduct in accordance with claim 1, wherein Y is a a-furyldioxime.

Claim 11

A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-alkyl.

Claim 12

A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-alkoxy.

Claim 13

A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-benzyl.

Claim 14

A boronic acid adduct in accordance with claim 1, wherein the boron derivative Z is B-cycloalkyl.

Claim 15

A boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(1,2-cyclohexanedione) 3 methyl boron.

Claim 16

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime) 3 1-methylpropyl boron.

Claim 17

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime)3 4-methylphenyl boron.

Claim 18

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime), cyclopentyl boron.

Claim 19

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(1,2-cyclohexanedione) 3 ethyl boron.

Claim 20

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine)(dimethyl glyoxime), 4-(t-butyl)phenyl boron.

Claim 21

A kit suitable for labeling with technetium-99m, said kit comprising: (i) a source of anion; (ii) a boronic acid derivative, or compounds which can react in situ to form a boronic acid derivative, having the formula or a pharmaceutically acceptable salt thereof, wherein R 3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl,alkoxy,carboxyalkyl,carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R 4 R 5 N-alkyl and R4and R 5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R s when taken together with nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle, and R 7 is hydrogen, alkyl or aryl; (iii) a dioxime having the formula or a pharmaceutically acceptable salt thereof, wherein R, and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6- membered nitrogen or oxygen containing heterocycle, or together R, and R2 are -(CR 8 R 9 ) n - wherein n is 3, 4, 5 or 6 and R 8 and R 9 are each independently hydrogen or alkyl; and (iv) a reducing agent.

Claim 22

A kit suitable for labeling with technetium-99m, said kit comprising: (i) a source of anion; (ii) a boronic acid derivative, or compounds which can react in situ to form a boronic acid derivative, having the formula or a pharmaceutically acceptable salt thereof, wherein R 3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl,alkoxy,carboxyalkyl,carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxyalkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R 4 R 5 N-alkyl and R4and R 5 are each independently hydrogen, alkyl, or arylalkyl, or R4 and R s when taken together with nitrogen atom to which they are attached form a 5 or 6-membered nitrogen containing heterocycle, and R 7 is hydrogen, alkyl or aryl; (iii) a dioxime having the formula or a pharmaceutically acceptable salt thereof, wherein R, and R2 are each independently hydrogen, halogen, alkyl, aryl, amino or a 5 or 6- membered nitrogen or oxygen containing heterocycle, or together R, and R2 are -(CR 8 R 9 ) n - wherein n is 3, 4, 5 or 6 and R 8 and R 9 are each independently hydrogen or alkyl; and (iv) a reducing agent.

Claim 23

A kit in accordance with claim 20, wherein the source of anion is a source of halide.

Claim 24

A kit in accordance with claim 20, wherein the source of anion is a source of chloride or bromide.

Claim 25

A kit in accordance with claim 20 wherein the dioxime is dimethyl glyoxime, 1,2-cyclohexanedione, 1,2,-ethanedione dioxime or α-furyldioxime.

Claim 26

A kit in accordance with claim 20, wherein the dioxime is dimethyl glyoxime.

Claim 27

A kit in accordance with claim 20, wherein the dioxime is 1,2-cyclohexanedione.

Claim 28

A kit in accordance with claim 20, wherein the reducing agent is a stannous salt.