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).sub.3 Z, wherein X is an anion; Y is a vicinal dioxime having the formula ##STR6## or a pharmaceutically acceptable salt thereof, wherein R 1 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 1 and R 2 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 Z is a boron derivative of the formula B--R.sub.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 4 and R 5 are each independently hydrogen, alkyl, or arylalkyl, or R 4 and R 5 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, α-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 α-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

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

Claim 19

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

Claim 20

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

Claim 21

The boronic acid adduct in accordance with claim 1, 99mTc (chlorine) (dimethyl glyoxime) 3 2-methyl-1-propyl boron.

Claim 22

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

Claim 23

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 ##STR7## or a pharmaceutically acceptable salt thereof, wherein R 3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxy-alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R 4 R 5 N-alkyl and R 4 and R 5 are each independently hydrogen, alkyl, or arylalkyl, or R 4 and R 5 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 ##STR8## or a pharmaceutically acceptable salt thereof, wherein R 1 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 1 and R 2 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 24

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 ##STR7## or a pharmaceutically acceptable salt thereof, wherein R 3 is hydroxy, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, carboxyalkyl, carboxyalkenyl, hydroxyalkyl, hydroxyalkenyl, alkoxyalkyl, alkoxy-alkenyl, haloalkyl, haloalkenyl, aryl, arylalkyl, or R 4 R 5 N-alkyl and R 4 and R 5 are each independently hydrogen, alkyl, or arylalkyl, or R 4 and R 5 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 ##STR8## or a pharmaceutically acceptable salt thereof, wherein R 1 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 1 and R 2 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 25

A kit in accordance with claim 22, wherein the source of anion is a source of halide.

Claim 26

A kit in accordance with claim 22, wherein the source of anion is a source of chloride or bromide.

Claim 27

A kit in accordance with claim 22 wherein the dioxime is dimethyl glyoxime, 1,2-cyclohexanedione dioxime, 1,2-ethanedione dioxime or α-furyldioxime.

Claim 28

A kit in accordance with claim 22, wherein the dioxime is dimethyl glyoxime.

Claim 29

A kit in accordance with claim 22, wherein the dioxime is 1,2-cyclohexanedione dioxime.

Claim 30

A kit in accordance with claim 22, wherein the reducing agent is a stannous salt.