Back to results
US 2002/0054853 A1Published application
Rhenium and technetium complexes containing a hypoxia-localizing moiety
AssigneeBracco International B.V.
InventorsKaren Linder, Adrian D. Nunn, David P. Nowotnik, Kondareddiar Ramalingam, Richard J. DiRocco, William L. Rumsey, John P. Pirro
Life of this patent
Estimating the term…
Abstract
Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprising a metal, preferably radionuclide of rhenium or technetium; a hypoxia-localizing moiety; and, a complexing ligand, wherein said ligand and said radionuclide combined have cell membrane permeabilities greater than that of sucrose, are disclosed.
Claims84
A compound of the formulae
- 48
- where at least one R is —(A)p—R2 where (A) is a linking group and R2 is a hypoxia localizing moiety;
- and wherein the other R groups are the same, or different and are independently selected from hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, aryl, —COOR3,
- 49
- —NH2, hydroxyalkyl, alkoxyalkyl, hydroxyaryl, haloalkyl, arylalkyl, -alkyl-COOR3, -alkyl-CON(R3)2, -alkyl-N(R3)2, -aryl-COOR3, -aryl-CON(R3)2, -aryl-N(R3)2, 5- or 6-membered nitrogen- or oxygen-containing heterocycle;
- or two R groups taken together with the one or more atoms to which they are attached form a carbocyclic or heterocyclic, saturated or unsaturated spiro or fused ring which may be substituted with R groups;
- R1 is hydrogen, a thiol protecting group or —(A)p—R2;
- R3 is hydrogen, alkyl or aryl;
- m=2 to 5;
- p=0 to 20.
7 more elements
A complex of a metal and a ligand, which ligand includes a hypoxia-localizing moiety,
- wherein said complex has a permeability through cell membranes greater than that of 14C-sucrose.
A process for preparing an alkylene diamineoxime comprising reacting an alkylene diamine with two equivalents of a haloketone to provide an alkylene diaminediketone which is thereafter converted to said alkylene diaminedioxime;
- or
- reacting an alkylene diamine with one equivalent of a first haloketone and reacting the resulting product with one equivalent of a second haloketone and thereafter converting to said alkylene diaminedioxime;
- or
- reacting an alkylene diamine with one equivalent of a chloronitroso, then reacting the product with a haloketone, thereafter converting to said alkylene diamine dioxime.
1 more element
A process for preparing a compound of the formula
- 62
- where at least one R is —(A)p—R2 where (A)p is a linking group and R2 is a hypoxia localizing moiety;
- and wherein the other R groups are the same, or different and are independently selected from hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, aryl, —COOR3,
- 63
- —NH2, hydroxyalkyl, alkoxyalkyl, hydroxyaryl, haloalkyl, arylalkyl, -alkyl-COOR3, -alkyl-CON(R3)2, -alkyl-N(R3)2, -aryl-COOR3, -aryl-CON(R3)2, -aryl-N(R3)2, 5- or 6-membered nitrogen- or oxygen-containing heterocycle;
- or two R groups taken together with the one or more atoms to which they are attached form a carbocyclic or heterocyclic, saturated or unsaturated spiro or fused ring which may be substituted with R groups;
- R3 is hydrogen, alkyl or aryl;
- m=2 to 5;
- and,
- p=0 to 20;
- which process comprises
- reacting a compound of the formula
- 64
- with two equivalents of a haloketone of the formula
- 65
- to produce a dixetone of the formula
- 66
- which is thereafter converted to the corresponding dioxime products;
- reacting a compound of the formula
- 67
- with one equivalent of a first haloketone of the formula
- 68
- to provide an intermediate of the formula
- 69
- which is thereafter reacted with one equivalent of a second haloketone of the formula
- 70
- wherein at least one of the R groups on said second haloketone differs from the corresponding R groups on said first haloketone, to provide an intermediate of the formula
- 71
- and thereafter converting to the corresponding dioxime wherein the R groups substituting said first amine oxime portion of the compound of formula A differ from the R groups substituting said second amine oxime portion.
26 more elements
A process for preparing a compound of the formula
- 72
- where at least one R is —(A)p—R2 where (A)p is a linking group and R2 is a hypoxia localizing moiety;
- and wherein the other R groups are the same, or different and are independently selected from hydrogen, halogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, aryl, —COOR3,
- 73
- —NH2, hydroxyalkyl, alkoxyalkyl, hydroxyaryl, haloalkyl, arylalkyl, -alkyl-COOR3, -alkyl-CON(R3)2, -alkyl-N(R3)2, -aryl-COOR3, -aryl-CON(R3)2, -aryl-N(R3)2, 5- or 6-membered nitrogen- or oxygen-containing heterocycle;
- or two R groups taken together with the one or more atoms to which they are attached form a carbocyclic or heterocyclic, saturated or unsaturated spiro or fused ring which may be substituted with R groups;
- R3 is hydrogen, alkyl or aryl;
- m=2 to 5;
- and,
- p=0 to 20;
- which process comprises:
- a) reacting a compound of the formula
- 74
- where s is 0 to 4 and t is 0 to 4 with the proviso that s+t is not greater than 4 with two equivalents of a compound the formula
- 75
- where halogen is Br, Cl or I, to provide a diketone of the formula
- 76
- and thereafter converting the diketone to the corresponding dioxime;
- or
- b) reacting a compound of the formula
- 77
- with one equivalent of a first compound of the formula
- 78
- to provide a compound of the formula
- 79
- and thereafter reacting with a compound of the formula
- 80
- where R′=R but where one of the R′ groups must be —(A)p—R2 to provide the diketone
- 81
- (where one of the R′ must be —(A)p—R2) which is thereafter converted to the corresponding dioxime.
27 more elements
Dependencies are inferred from the claim text.