Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: ##STR00001##
or a salt therof. R.sub.1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R.sub.2 is —N.sup.+H.sub.3, —N.sup.+H.sub.2Z, —N.sup.+HZ.sub.2, or —N.sup.+Z.sub.3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: ##STR00001##
or a salt therof. R.sub.1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R.sub.2 is —N.sup.+H.sub.3, —N.sup.+H.sub.2Z, —N.sup.+HZ.sub.2, or —N.sup.+Z.sub.3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

The novel bisphosphonic acid ester derivatives represented by the following formula (1):

Y—Cy—(NH).sub.m—(CH.sub.2).sub.n—C(X)(PO(OR.sup.1)(OR.sup.2)).sub.2   (1)

wherein each symbol is as defined in the DESCRIPTION, which has an amino group substituted by a heterocyclic group or a heterocyclic group containing a nitrogen atom, and the acid moiety is esterified with a POM group, an n-butanoyloxymethyl (BuOM) group and the like, exhibit a superior direct or indirect cytotoxicity effect on tumor cells and virus infected cells.

The novel bisphosphonic acid ester derivatives represented by the following formula (1):

Y—Cy—(NH).sub.m—(CH.sub.2).sub.n—C(X)(PO(OR.sup.1)(OR.sup.2)).sub.2   (1)

wherein each symbol is as defined in the DESCRIPTION, which has an amino group substituted by a heterocyclic group or a heterocyclic group containing a nitrogen atom, and the acid moiety is esterified with a POM group, an n-butanoyloxymethyl (BuOM) group and the like, exhibit a superior direct or indirect cytotoxicity effect on tumor cells and virus infected cells.

The disclosure provides a compound comprising bisphosphonate functional group and chelating agent. The bisphosphonate functional group part has high affinity for bone tissue, and the chelating agent part has high affinity for metal tracer such as radioisotope. The disclosed compound could be rapidly adsorbed onto the bone surface, and could steady emit ionizing radiation. Therefore, the disclosed compound is suitable for bone scanning technology to find abnormalities in bone.

The disclosure provides a compound comprising bisphosphonate functional group and chelating agent. The bisphosphonate functional group part has high affinity for bone tissue, and the chelating agent part has high affinity for metal tracer such as radioisotope. The disclosed compound could be rapidly adsorbed onto the bone surface, and could steady emit ionizing radiation. Therefore, the disclosed compound is suitable for bone scanning technology to find abnormalities in bone.

Disclosed are chelates resulting from the complexation of bifunctional do2pa derivatives ligands of formula (I), wherein the substituents R.sup.1, R.sup.1′, R.sup.2, R.sup.2′, R.sup.3, R.sup.3′, L.sup.1, L.sup.1′, L.sup.2 and L.sup.2′ are defined as in the claims, with metallic cations, especially Pb(II) and Bi(III). Also disclosed are bifunctional do2pa derivatives ligands of formula (I), as well as the use of chelates in nuclear medicine and the use of ligands in cations detection or epuration of effluents.

##STR00001##

Disclosed are chelates resulting from the complexation of bifunctional do2pa derivatives ligands of formula (I), wherein the substituents R.sup.1, R.sup.1′, R.sup.2, R.sup.2′, R.sup.3, R.sup.3′, L.sup.1, L.sup.1′, L.sup.2 and L.sup.2′ are defined as in the claims, with metallic cations, especially Pb(II) and Bi(III). Also disclosed are bifunctional do2pa derivatives ligands of formula (I), as well as the use of chelates in nuclear medicine and the use of ligands in cations detection or epuration of effluents.

##STR00001##