Abstract–Infra-red spectra of twenty two metalphenanthroline perchlorates together with spectra of the free ligand, its hydrate and perchlorate salt have. Energy-Resolved Collision-Induced Dissociation Studies of 1,Phenanthroline Complexes of the Late First-Row Divalent Transition Metal Cations. A61K51/ Organic compounds complexes or complex-forming .. Embodiment The conjugate of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8 and 9, For example, in case the first targeting moiety is targeting NTR1 the first targeting moetiy is Such chelators include, but are not limited to linear, macrocyclic.
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Alkyllithium reagents form deeply colored derivatives with phenanthroline. It is, however, well known that the radionuclide chemistry and associated linkages are crucial particularly with respect to the attachment to the compound of an effector which provides the signal needed for diagnosis or which provides the therapeutically effective activity. Such methods comprise, but are not limited to, receptor autoradiography Reubi et al.
More chemical possibilities open up if one synthesizes a tBu protected form of the amino acid 56 which is described in exam le Phen system were studied at various molar ratios ranging from 1: The conjugate of any one of embodiments 1 to 62, wherein the first target is same as the second target.
The conjugate of any one of embodiments 47 to 49, wherein the linkage is selected from the group comprising an amide linkage, a sulfonamide linkage, a urea linkage, a thiourea linkage, a thioether linkage, an ether linkage, a carbamate linkage, an amine linkage, a triazole linkage, an oxime linkage, a hydrazone, a disulfide linkage, a pyrazine linkage and a dihydro-pyrazine linkage.
A composition, preferably a pharmaceutical composition, wherein the composition comprises a compound according to any one of embodiments 1 to 78 and a pharmaceutically acceptable excipient. The conjugate of embodiment 96, wherein the tumor is selected from the group comprising ductal pancreatic adenocarcinoma, small cell lung cancer, prostate cancer, colorectal cancer, breast cancer, meningioma, Ewing’s sarcoma, pleural mesothelioma, head and neck cancer, non-small cell lung cancer, gastrointestinal stromal tumors, uterine leiomyoma and cutaneous T-cell lymphoma, preferably ductal pancreatic adenocarcinoma, small cell lung cancer, prostate cancer, colorectal cancer, breast cancer, meningioma, Ewing’s sarcoma, and indications subject to group A defined herein.
Carcinomatosis; Epithelioma, benign; Epithelioma, malignant; Large cell carcinoma. It is within the present invention that any embodiment of the linker moiety as disclosed herein and in particual embodiments of the linker moiety VIII to XV as disclosed herein, can be realized in any of the embodiment of the conjugate of the invention and in particular phenanhhroline embodiments I to VII of the conjugate of the invention as disclosed herein.
Preferred methods are receptor autoradiography Reubi et al. Such effector can be attached to the compound either directly or through a connecting moiety.
The conjugate of any one of embodiments 93 to 97, wherein Effector complfxes a radioactive metal, wherein preferably the radioactive metal is phenanthrolin by Acceptor, wherein Acceptor is a chelator.
A preferred linkage is a chemical bond or a plurality of chemical bonds. The method according to any one of embodiments towherein the disease is a disease involving neurotensin receptor, preferably the disease is a disease involving neurotensin receptor 1, or from a disease involving a target targeted by compldxes first targeting moiety TM1 or by the second targeting moiety TM2.
As shown in Figure 5the species is major species found in an aqueous solution at pH 4. It is within the present invention that a target to which the further targeting moiety of the conjugate of the invention is capable of binding, is a target that is expressed heterogeneously in an indication, preferably in an oncology indication, more preferably in any indication related to oncology. As shown in Figure 4the species is the primary species prevalent in an aqueous solution at pH 5.
The conjugate of any one of embodiments 2 to 71, wherein the Effector is a diagnostically active nuclide or a therapeutically active nuclide, wherein the diagnostically active nuclide and the therapeutically active radionuclide is individually and independently selected from the group comprising m In, 99m Tc, 67 Ga, 52 Phenanthtoline, 68 Ga, 72 As, m In, 97 Ru, Pb, 62 Cu, “Cu, 51 Cr, 52m Mn, Gd, 64 Cu, 89 Zr, and ,77 Lu, ,86 Re, 90 Y, 67 Cu, 68 Ga, 69 Er.
The conjugate of any one of embodiments 2 to 58, preferably embodiment 57, wherein the Effector is a diagnostically active nuclide, preferably a diagnostically active radionuclide, or a therapeutically active nuclide, preferably a therapeutically active radionuclide. However, the software rejected all other species except. It is, however, also within the present invention that the conjugate of the invention does not comprise a linker moiety.
In an embodiment and as preferably used herein, a diagnostic agent or a diagnostically active agent is a compound which is suitable for or useful in the diagnosis of a disease. In preferred embodiment the covalent linkages are provided by the first adaptor moiety ADl, the linker moiety LM and the second adaptor moiety AD2, or any combination thereof. In this respect, numerous investigations in the properties and applications of ruthenium II complexes with 1,phenanthroline phen as a ligand or mixed with other ligands are reported [ 25 — 27 ].
Phenanthroline – Wikipedia
The following table summarizes the expression of NTR1 as described in the prior art indicating the tissue, degree of expression, detection method and the respective references.
The conjugate of any one of embodiments 1 to 77, wherein the con ugate is different from compound 89including the 18 F analog of this compound:. The ligands and their metal complexes were evaluated for in vitro antibacterial activities against strains of two Gram-positive S.
R 3R 4 and R 5 are each and independently selected from the group consisting of hydrogen and C! A variety of substituted derivatives of phen have been examined as ligands. Depending on the type of reactive group provided by the targeting moeity, the adaptor moiety provides a reactive group which is complementary to such reactive group provided by the targeting moiety.
It is also involved in regulation of dopamine pathways. It will be understood by a person skilled in the art that such trapping of the effector bearing agonist may go along with the release of the effector from the agonist. The conjugate of any one of embodiments 1, 2 and 12, wherein. Because of this, this kind of compound of the prior art acts as an agonist to NTRl.
In a preferred embodiment, the two reactive groups provided by the adapter moiety are different. The conjugate of any one of embodiments 79 to 83, wherein Effector is a radioactive metal, wherein preferably the radioactive metal is chelated by Acceptor, wherein Acceptor is a chelator.
The conjugate of any one of embodiments 1, 2 and 3, wherein AA- COOH is an amino acid selected from the group consisting of 2-aminoadamantane carboxylic acid and cyclohexylglycine.
Due to the binding characterisitics of the conjugate of the invention it is also possible to target a first target targeted by the first targeting moiety and thus a cell, tissue and organ, respectively, expressing such first target, independently from the targeting of a second target targeted by the second targeting moiety and thus a cell, tissue and organ, respectively, expressing such second target; and vice versa.
From Wikipedia, the free encyclopedia. Galanin Galanin Galmic Galnon Antagonists: The conjugate of any one of embodiments 1 to 52, wherein the linker moiety LM is present. In a further embodiment of the conjugate of the invention the antibody is a human antibody, a humanized antibody, a chimeric antibody, a sub-primate antibody a murine antibody or an antibody from other species, i.
The Phen Merck, A specific type of amine linkage is one, wherein an N atom is bound to an aliphatic C atom, whereby such linkage is also referred to as alkylamine linkage -N-C alk macrocycljc. Only for colon weak or moderate expression under physiological conditions is described.
S45 hpenanthroline, S60S In another embodiment of the conjugate of the invention the conjugate comprises, in terms of an adapter moiety, only a first adapter moiety ADl and a second adapter moiety AD2. This includes stabilization of different oxidation states and modulation of the solvophilicity and electrophilic and nucleophilic properties of the metal ion [ 4 — 6 ].
In an embodiment of the conjugate of the invention the further targeting moiety is preferably a targeting moiety having a selectivity factor of equal to ore more than 10,; of equal to or more than ; of equal to or more than ; of equal to or more than 50; of equal to or more than 10; of equal to or moetoy than 5 or of equal to or more than 2 to an anti-target. In an embodiment and macrcyclic preferably used herein, C 2 -C 5 alkyl means each and individually any of ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2- methyl-butyl, 3 -methyl -butyl, 3-pentyl, 3-methyl-butyl, 2-methyl-butyl and 2,2- dimethylpropyl.
Moreover, the change in the intensity may explain the change in the relative amount of water molecules in 1,phenanthroline monohydrate and the complexes. The conjugate of any one of embodiments 1 to 36, wherein the first adapter moiety AD1 mediates linkage to the first targeting moiety TM1 and to an adjacent moiety, wherein the adjacent moiety is selected from the group comprising linker moiety LM, building block moiety [X] abranching moiety Y, building block moiety [Z]b, second adapter moiety AD2 and second targeting moiety TM2.
In a preferred embodiment thereof, the adapter moiety forms a thioether linkage with a sulfur atom of the targeting moiety. It is within the present invention that such selectivity of the further targeting moiety is shown by any embodiment of such further targeting moiety.