Crowned dithiocarbamate metal complexes and methods for their use
OwnerShuang Liu, Zhengjie Heinventors
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Abstract
Compositions containing crowned dithiocarbamate metal complexes and methods of using these compositions; neutral and cationic radioactive metal-nitrido complexes of crowned dithiocarbamates (DTCs) and methods of using these complexes as radiopharmaceuticals for diagnosis and treatment of cardiovascular disorders, infectious diseases, and cancer; tripodal chelatormetal complexes of crowned DTCs and methods of using these complexes for treating diseases such as those characterized by nitric oxide overproduction; and methods of using crowned DTCs for heavy metal detoxification are described.
Claims49
A composition comprising a compound comprising a formula (M≡N)L1 and pharmaceutically acceptable salts thereof;
- wherein N is nitrogen;
- M is a transition metal;
- and
- L1 is a first crowned dithiocarbamate, wherein the first crowned dithiocarbamate comprises a first crown ether-containing group of formula [(CH2)a—O]b—(CH2)c, wherein a is at least 2, b is at least 3, and c is at least 2.
A composition comprising a compound comprising a formula:
- and pharmaceutically acceptable salt thereof;
- wherein M is a transition metal selected from the group consisting of Fe(II), Fe(III), Mn(II), Mn(III), Co(II), Co(III), Ni(II), Cu(II), Zn(II), Ru(II), Ru(III), Pd(II), and Pt(II);
- p and p′ are integers and are independently selected from 0-2;
- R1 and R2 comprise a crown ether-containing group of formula [(CH2)a—O]b—(CH2)c, wherein a is at least 2, b is at least 3, and c is at least 2, or wherein R1 and R2 together comprise the crown ether-containing group;
- L6 is a tripodal chelator with a formula selected from the group consisting of
- wherein U is selected from the group consisting of R13B, CR13, and P(═O);
- A1, A2 and A3 are imine-N containing heterocycles;
- A4, A5 and A6 are selected from the group consisting of NR10, PR10, and S;
- R10, R11 and R12 are selected from a group of formula —(CH2)g—, wherein g is 2-5;
- R13 is selected from the group consisting of H, alkyl and aryl;
- and
- R14 is selected from the group consisting of H, alkyl, aryl, and alkoxyalkyl.
A method for radioimaging a subject comprising:
- a) providing
- i) a subject;
- and
- ii) a composition comprising a compound comprising a formula (M≡N)L1 and pharmaceutically acceptable salts thereof;
- b) administering the composition to the subject;
- and
- c) scanning at least a portion of the subject using a radioimaging device;
- wherein N is nitrogen;
- M is a radioactive transition metal;
- and
- L1 is a first crowned dithiocarbamate, wherein the first crowned dithiocarbamate comprises a first crown ether-containing group of formula [(CH2)a—O]b—(CH2)c, wherein a is at least 2, b is at least 3, and c is at least 2.
A method of treating a disease resulting from overproduction of nitric oxide or reactive oxygen species, comprising:
- a) providing:
- i) a subject with a disease;
- and
- ii) a composition comprising a compound comprising a formula:
- and pharmaceutically acceptable salt thereof;
- and
- b) administering the composition to the subject;
- wherein M is a transition metal selected from the group consisting of Fe(II), Fe(III), Mn(II), Mn(III), Co(II), Co(III), Ni(II), Cu(II), Zn(II), Ru(II), Ru(III), Pd(II), and Pt(II);
- p and p′ are integers and are independently selected from 0-2;
- R1 and R2 comprises a crown ether-containing group of formula [(CH2)a—O]b—(CH2)c, wherein a is at least 2, b is at least 3, and c is at least 2, or wherein R1 and R2 together comprise the crown ether-containing group;
- L6 is a tripodal chelator with a formula selected from the group consisting of:
- wherein U is selected from the group consisting of R13B, CR13, and P(═O);
- A1, A2 and A3 are imine-N containing heterocycles;
- A4, A5 and A6 are selected from the group consisting of NR10, PR10, and S;
- R10, R11 and R12 are selected from a group of formula (CH2)g—, wherein g is 2-5;
- R13 is selected from the group consisting of H, alkyl and aryl;
- and
- R14 is selected from the group consisting of H, alkyl, aryl, and alkoxyalkyl.
A method of treating metal poisoning, comprising:
- a) providing:
- i) a subject with metal poisoning, and
- ii) a composition comprising a crowned dithiocarbamate;
- and
- b) administering the composition to the subject;
- wherein the crowned dithiocarbamate comprises a crown ether-containing group of formula [(CH2)a—O]b—(CH2)c, wherein a is at least 2, b is at least 3, and c is at least 2.
Dependencies are inferred from the claim text.