1. Compounds of general formula I
Ar-(L-K)n(I)
in which
K means a cyclic non-radioractive metal complex of the DOTA type,
L means a linker,
Ar means an aromatic radical, which contains a polycondensated aromatic hydrocarbon, and
n means the numbers 1 or 2.
2. Compounds according to claim 1, characterized in that Ar stands for a radical
13
with the meaning
A: a direct bond,
a methylene group CH2,
a dimethylene ether group CH2OCH2,
B: a hydrogen atom,
a carbonyl group CO,
C: a hydroxyl group OH,
an oxygen group O.
an ether group OR1, in which R1 means an alkyl radical with 1-3 carbon atoms, whereby substituents B and C in the molecule are respectively identical,
for a radical
14
with the meaning
D: a hydrogen atom,
an ether group OR, with R1 in the above mentioned meaning,
for radical
15
with the meaning
B and C as described above,
for a radical
16
with the meaning
E: a hydrogen atom,
An ether group OR1,
A dialkylamino group N(R1)2, whereby R1 has the above-mentioned meaning,
o: a number between 2-10,
for a radical
17
with the meaning
E1, E2: independently of one another, in the meaning of E,
F1, F2: independently of one another, for a hydrogen atom H or the radicals
18
with o in the above-mentioned meaning,
and provided that one of substituents F1 or F2 stands for a hydrogen atom and that a refers to the binding site orientated to the aromatic compounds and refers to the binding site orientated to the metal complex.
3. Compounds according to claim 1, wherein
L stands for a linker in the meaning of a hydrazine group NHNH, a C2-C20 carbon chain with terminal NH, which can be linear or branched, saturated or unsaturated and optionally is interrupted by 1-6 oxygen atoms, 1-2 phenylene groups, 1-2 cyclohexylidene groups, 1-2 groups NHCO or CONH, 1-2 groups CH2CONHNH or NHNHCOCH2 and optionally is substituted with 1-2 hydroxyl groups, with 1-2 methoxy groups, with 1-2 carboxy groups.
4. Compounds according to claim 1, wherein
K stands for a metal complex of general formula II
19
with the meaning
R: a hydrogen atom,
a methyl group,
Z1, Z2, Z3: a metal ion equivalent of the atomic numbers 25, 26 as well as 58-70,
U: a C1-C10 carbon chain, linear or branched, saturated or unsaturated, optionally interrupted by 1-2 oxygen atoms, by a phenylene group, by a cyclohexylidene group, by one or two groups NHCO or CONH, optionally substituted with one to two CO2H groups, with one to three hydroxyl groups, one to three methoxy or alkoxy groups,
or for a metal complex of general formula III
20
with the meaning
Z1, Z2, Z3: as indicated above.
V: a phenylene, phenylenoxymethyl- –C6H4OCH2- group whereby indicates the binding site orientated to the aromatic compound and indicates the binding site orientated to the metal complex,
a C1-C20 carbon chain, linear or branched, saturated or unsaturated, optionally interrupted by one to two oxygen atoms, by a phenylene group, by a cyclohexylidene group, by one or two groups NHCO or CONH, optionally substituted with one to two CO2H groups with one to three hydroxyl groups, one to three methoxy or alkoxy groups.
5. Compounds according to claim 1, wherein
L stands for a radical
NHNH
-CH2CONHNH
NHCH2CH2NH
NH CH2CH2CH2CH2NH
NH(CH2)3NH
NH(CH2)5NH
NH(CH2)2O(CH2)2NH
-NH(CH2)k-CONH(CH2)m-NH- mit k1-10; m0-10,
-NH(CH2CH2O)2CH2CH2NH-with
-NHCH(CH2)4NH-
COOH
NHCH2CHOHCH2NH
21
-NH(CH2CH2O)3CH2NH-,
22
23
and ans have the meanings given in claim 4.
6. Compounds according to claims 1 and 4, wherein
U stands for a group
CH2
CH2CH2
C6H4
CH2OCH2CH2.
7. Compounds according to claim 1, wherein
V stands for a group
CH2OC6H4
C6H4
CH2CH2
CH2.
8. Compounds according to claim 1, wherein the central ion of metal complex K is a gadolinium ion, iron ion or manganese ion.
9. Pharmaceutical agent that contains at least one compound according to claim 1, optionally with the additives that are commonly used in galenicals.
10. Use of at least one compound according to claim 1 for the production of agents for MR imaging of necrosis and infarction.
11. Process for the production of compounds according to claim 1, wherein compounds of general formula IV
Ar(L-H)n(IV)
are reacted with complexes or complexing agents of general formula V
K-X(V)
in which
Ar, L, K and n have the meaning that is mentioned in claim 1, and X stands for a hydroxy group or a group that activates the carboxylic acid, and optionally then is reacted (if K-X stands for a complexing agent) in a way that is known in the art with a metal oxide or metal salt of an element of atomic numbers 25, 26 or 58-70 and optionally then acid hydrogen atoms that are still present in the complexes that are thus obtained are substituted completely or partially by cations of inorganic andor organic bases, amino acids or amino acid amides.
12. Process for the production of the pharmaceutical agents according to claim 9, wherein the metal complex that is dissolved or suspended in water or physiological salt solution, optionally with the additives that are commonly used in galenicals, is brought into a form that is suitable for enteral or parenteral administration.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for manufacturing a semiconductor device, comprising:
providing a substrate having a P-type metal oxide semiconductor (PMOS) device region and N-type metal oxide semiconductor (NMOS) device region;
forming a first gate structure over the substrate in the PMOS device region and a second gate structure over the substrate in the NMOS device region;
forming recessed epitaxial silicon germanium regions in the substrate on opposing sides of the first gate structure; and
forming first sourcedrain regions on opposing sides of the first gate structure and second sourcedrain regions on opposing sides of the second gate structure;
annealing the first sourcedrain regions and second sourcedrain regions to form activated first sourcedrain regions and activated second sourcedrain regions; and
forming recessed epitaxial carbon doped silicon regions in the substrate on opposing sides of the second gate structure after annealing.
2. The method of claim 1, wherein forming first sourcedrain regions includes forming first extension implants and first sourcedrain implants; wherein forming second sourcedrain regions includes forming second extension implants and second sourcedrain implants; wherein annealing the first sourcedrain regions includes annealing the first extension implants and first sourcedrain implants to form the activated first sourcedrain regions; and wherein annealing the second sourcedrain regions includes annealing the second extension implants and second sourcedrain implants to form the activated second sourcedrain regions.
3. The method of claim 1 wherein the epitaxial carbon doped silicon regions are doped with phosphorous.
4. The method of claim 1 wherein the recessed epitaxial silicon germanium regions are located a distance (d1) from sidewalls of the first gate structure and further wherein the recessed epitaxial carbon doped silicon regions are located a greater distance (d2) from sidewalls of the second gate structure; wherein the distance (d1) is related to a thickness of gate sidewall spacers; and wherein the distance (d2) is related to a thickness of the gate sidewall spacers and sourcedrain spacers.
5. The method of claim 1, wherein forming recessed epitaxial silicon germanium regions includes forming a masking layer protecting the NMOS device region and exposing at least a portion of the PMOS device region, subjecting exposed portions of the PMOS device region to an etch to form first recesses, and growing epitaxial silicon germanium within the first recesses; and wherein forming recessed epitaxial carbon doped silicon regions includes forming the masking layer protecting the PMOS device region and exposing at least a portion of the NMOS device region, subjecting exposed portions of the NMOS device region to an etch to form second recesses, and growing epitaxial carbon doped silicon within the second recesses.
6. The method of claim 1, further including forming interlevel dielectric layers over the first gate structure and the second gate structure, wherein the interlevel dielectric layers include interconnects therein for contacting the first gate structure and the second gate structure.
7. A semiconductor device formed according to the method described in claim 1.
8. A semiconductor device, comprising:
a p-type metal oxide semiconductor (PMOS) device region located over a substrate, including:
a first gate structure located over the substrate;
activated first sourcedrain regions located in the substrate on opposing sides of the first gate structure; and
recessed epitaxial silicon germanium regions located in the substrate on opposing sides of the first gate structure; and
an N-type metal oxide semiconductor (NMOS) device region located over the substrate, including:
a second gate structure located over the substrate;
activated second sourcedrain regions located on opposing sides of the second gate structure; and
recessed epitaxial carbon doped silicon regions located in the substrate and adjacent the activated second sourcedrain regions, and further wherein a physical interface separates the recessed epitaxial carbon doped silicon regions and the activated second sourcedrain regions.
9. The semiconductor device of claim 8, further including interlevel dielectric layers located over the first gate structure and the second gate structure, wherein the interlevel dielectric layers include interconnects therein for contacting the first gate structure and the second gate structure.