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US 5,516,940 AGranted
Multifunctional ligand for use as a diagnostic or therapeutic pharmaceutical
AssigneeThe Curators of the University of Missouri
InventorsKattesh V. Katti, Wynn A. Volkert, Alan R. Ketring, Prahlad R. Singh
Life of this patent
Estimating the term…
Abstract
A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises either a phosphorous or germanium core and at least two hydrazine groups forming a ligand for bonding to a metal extending from the phosphorous or germanium core.
Claims13
A compound for use as a diagnostic or therapeutic pharmaceutical, or MRI contrast agent, said compound comprising:
- a phosphine core, and two hydrazine groups forming a ligand bound to a transition metal extending from said phosphorous core wherein said ligand is of the formula ##STR16## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 are all the same or different and are H,
- an alkyl group selected from Me, Et, n- or i-propyl, n-, i- or t-butyl, n-hexyl, --CH.sub.2 COOH, --CH(OH)CH.sub.2 OH),
- cyclohexyl,
- an alkylamine group selected from --NMe.sub.2, NHMe, (CH.sub.2).sub.n NMe.sub.2, (CH.sub.2).sub.n NHMe, --(CH.sub.2).sub.n NH.sub.2,
- an alkoxy group selected from --O(CH.sub.2).sub.n CH.sub.3, (CH.sub.2).sub.n OCH.sub.3, --(CH.sub.2).sub.n --COOH, --(CH.sub.2).sub.n SH,
- an aromatic group of the formula --C.sub.6 H.sub.4 R wherein R=H, NH.sub.2, COOH, OH, NCS, CHO, activated esters, acid anhydrides, N-hydroxy succinamide, and SiMe.sub.3 ;
- R.sup.5 is H, OCH.sub.3 --CH(OH)--CH.sub.2 OH, Me or Ph E is O or S;
- Q is H, --CH.sub.2 Ph or --CHPh wherein in each instance Ph is unsubstituted or substituted with OH, COOH, O alkyl wherein alkyl are from 1 to 4 carbon atoms, NH.sub.2, NH(alkyl C.sub.1-4) or NH(alkyl C.sub.1-4).sub.2, or halogen such as chlorine, fluorine, bromine or iodine or Q can be --CH.sub.2 piperazino or --CH piperazino;
- and wherein when R.sup.5 is Ph, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are not methyl or ethyl and wherein when R.sup.5 is Ph, E is O, and Q is H, then R.sup.3 and R.sup.4 are not phenyl.
6 more elements
A compound for use as a diagnostic, therapeutic pharmaceutical, or MRI contrast agent of the formula ##STR17## forming a ligand bound to a transition metal wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 are all the same or different and are H,
- an alkyl group selected from (Me, Et, n- or i-propyl, n-, i- or t-butyl, or n-hexyl,
- cyclohexyl,
- an alkylamine group selected from --NMe.sub.2, NHMe, (CH.sub.2).sub.n NMe.sub.2, (CH.sub.2).sub.n NHMe, --(CH.sub.2).sub.n NH.sub.2,
- an alkoxy group selected from --O(CH.sub.2).sub.n CH.sub.3, (CH.sub.2).sub.n OCH.sub.3,
- an aromatic of formula --C.sub.6 H.sub.4 R wherein R=H, NH.sub.2, COOH, NCS, CHO, activated esters, acid anhydrides, N-hydroxy succinamide, and SiMe.sub.3 ;
- R.sup.5, R.sup.6 are all the same or different and are H, Me or Ph;
- E is O or S.
4 more elements
A compound for use as a diagnostic, therapeutic pharmaceutical, or MRI contrast agent selected from the group consisting of the formulas ##STR18## forming a ligrand bound to a transition metal wherein E is O or S;
- wherein R.sup.5 is H, --OCH.sub.3, --CH(OH)--CH.sub.2 OH, CH.sub.3, Ph;
- wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are the same or different and are H, cyclohexyl, --CH.sub.2 COOH, --CH(OH)CH.sub.2 OH,
- an alkyl group of formula (C.sub.0-6)NYZ wherein each of Y and Z is hydrogen or lower alkyl C.sub.1 -C.sub.4,
- straight or branched alkoxy having from 1 to 6 carbon atoms,
- --(CH.sub.2).sub.n --OCH.sub.3 wherein .sub.n is 1 to 6,
- phenyl or phenyl substituted with OH, NH.sub.2, COOH, NCS, CHO, activated esters, acid anhydrides, N-hydroxysuccinamide, SiMe.sub.3 ;
- Q is H, --CH.sub.2 Ph or --CHPh wherein each Ph is unsubstituted or substituted with OH, COOH, alkyl wherein alkyl has from 1 to 4 carbon atoms, alkyl (C.sub.0-6)NYZ wherein Y and Z are as defined above or Ph is substituted with halogen, or Q is --CH.sub.2 piperazino or .dbd.CH piperazino;
- and wherein when the ligand is the dihydrazine E, is O, Q is H, and R.sup.5 is Ph, then R.sup.4 and R.sup.4 are not Ph.
5 more elements
A compound for use as a diagnostic or therapeutic pharmaceutical, or MRI contrast agent, said compound comprising:
- a phosphine core, and at least two hydrazine groups forming a bis-hydrazine phosphine ligand bound to a transition metal extending from said phosphorous core of the formula ##STR19## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 are all the same or different and are H,
- an alkyl group selected from Me, Et, n- or i-propyl, n-, i- or t-butyl, n- hexyl, --CH.sub.2 COOH, --CH(OH)CH.sub.2 OH),
- cyclohexyl,
- an alkylamine selected from --NMe.sub.2, NHMe, (CH.sub.2).sub.n NMe.sub.2, (CH.sub.2).sub.n NHMe, --(CH.sub.2).sub.n NH.sub.2,
- an alkoxy group selected from --O(CH.sub.2).sub.n CH.sub.3, (CH.sub.2).sub.n OCH.sub.3, --(CH.sub.2).sub.n --COOH or --(CH.sub.2).sub.n SH,
- an aromatic of formula (--C.sub.6 H.sub.4 R wherein R=H, NH.sub.2, COOH, OH, NCS, CHO, activated esters, acid anhydrides, N-hydroxy succinamide, and SiMe.sub.3);
- R.sup.5 is H, OCH.sub.3 --CH(OH)--CH.sub.2 OH, Me or Ph;
- E is O or S;
- Q is H, --CH.sub.2 Ph or --CHPh wherein in each instance Ph is unsubstituted or substituted with OH, COOH, alkyl wherein alkyl are from 1 to 4 carbon atoms, NH.sub.2, NH(alkyl C.sub.1-4) or NH(alkyl C.sub.1-4).sub.2, or halogen such chlorine, fluorine, bromine or iodine or Q can be --CH.sub.2 piperazino or --CH piperazino;
- and wherein when R.sup.5 is Ph, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are not methyl or ethyl and wherein when R.sup.5 is Ph, E is O, and Q is H, then R.sup.3 and R.sup.4 are not phenyl.
7 more elements
A compound for use as a diagnostic or therapeutic pharmaceutical, or MRI contrast agent, said compound comprising:
- a phosphine core, and at least three hydrazine groups forming a tris-hydrazine phosphine ligand bound to a transition metal extending from said phosphorous core of the formula ##STR20## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 are all the same or different and are H,
- an alkyl selected from Me, Et, n- or i-propyl, n-, i- or t-butyl, n-hexyl,
- a cyclohexyl,
- an alkylamine selected from --NMe.sub.2, NHMe, (CH.sub.2).sub.n NMe.sub.2, (CH.sub.2).sub.n NHMe, --(CH.sub.2).sub.n NH.sub.2,
- an alkoxy selected from --O(CH.sub.2).sub.n CH.sub.3, (CH.sub.2).sub.n OCH.sub.3,
- an aromatic of formula --C.sub.6 H.sub.4 R wherein R=H, NH.sub.2, COOH, NCS, CHO, activated esters, acid anhydrides, N-hydroxy succinamide, and SiMe.sub.3 ;
- R.sup.5,R.sup.6 are all the same or different and are H, Me or Ph;
- and
- E is O or S.
6 more elements
Dependencies are inferred from the claim text.