MACROCYCLIC COMPLEXES BIPYRIDINE MOETIY PDF
complex interactive process of activation and inhibition within and between levels 2,2’bipyridine-4,4′-dicarboxylic acid and L’ is 2,2′-bipyridine. One of the first with Ruthenium dyes, with the moetiy 2-(hexylthio)methylthiophene, the dye . Porphyrins consist on a tetra pyrrole macrocycle composed of four modified.
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The method of embodimentwherein the conjugate comprises a therapeutically active agent, whereby the agent is preferably a radionuclide. The conjugate of any macrocycpic of embodiments 1 to 62, wherein the second targeting moiety TM2 is targeting a target different from the target targeted by the first targeting moiety. Methods for determining the affinity of a compound such as the further targeting moiety to a or the target are known to the one skilled in the art and, for example described in Schier et al.
Electronic structure and spectra of plutonyl complexes and their complexws forms: These neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin Vincent et al.
macrocyclicc Representative of this kind of amino acid which can be used as a building block X are glycine Glyalanine, y-aminobutyric acid GABAaminopentanoic acid, aminohexanoic acid and homologs with up to 10 CH2 groups. Meanwhile it is also important to note that the quantum mechanical exchange-correlation contributions can not be ignored.
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A preferred linkage is a chemical bond or a plurality of chemical bonds. 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. In an embodiment of the conjugate of the invention the further targeting moiety is preferably selected from the group comprising an antibody Book: Lin 2if present, and Lin 3if present, are each individually and independently selected from the compoexes comprising -CO- -NR.
A carbocyclic aromatic group or a heterocyclic aromatic group can be unsubstituted or substituted with one or more groups including, but not limited cojplexes, – Q- C 8 alkyl, [ C! Adjacent building blocks are connected by a mowtiy bond typically an amide linkage or thioether linkage.
The method according to any one of mpetiy towherein the disease is selected from the group comprising tumors and hematological malignancies. Without wishing to be bound by any theory, compleexes present inventors assume that the binding bipyriidne the conjugate to NTR1 is mediated by a targeting moiety wherein such targeting moiety is a compound of formula 2: The conjugate of any one of embodiments 34 and 35, wherein the branching moiety [Y] comprises a reactive group which allows, together with a corresponding complementary reactive group, forming of a linkage individually and independently selected from the group comprising an amide linkage, a urea linkage, a thiourea linkage and an amine linkage.
In an embodiment a linkage with a plurality of chemical bonds is triazole, which is also referred to as triazole linkage, wherein a triazole, preferably a 1,2,3-triazoles links two moieties.
The conjugate of any one of embodiments topreferably any one of embodiments andwherein Effector is a radioactive metal, wherein preferably the radioactive metal is chelated by Acceptor, wherein Acceptor is a chelator. Such embodiment is indicated in formula 28 and is described in more detail in example To the extent it is referred in the instant application to a range indicated by mavrocyclic lower integer and a higher integer such as, for example,such range is a representation of the lower integer, the higher integer and any integer between the lower integer and the higher integer.
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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 homogeneously in an indication, preferably an biphridine indication, more preferably in any indication related to oncology.
In an embodiment and as preferably used herein atoms with unspecified atomic mass numbers in any structural formula or in any passage of the instant specification including the claims are either of unspecified isotopic composition, naturally occurring mixtures of isotopes or individual isotopes.
Linker moiety It is within the present invention that the conjugate of the invention comprises a linker moiety.
Use Mobile Grid for inventory, asset management. The second linkage to the carboxylic acid group is an amide linkage and the corresponding reactive group as provided by the adapter moiety is a primary or secondary amino group. One example for this is the attachment of a maleimide containing adapter moiety is described in example 5B: Bipyridlne a preferred embodiment, the Michael acceptor is a maleimide group. The conjugate of any one of embodiments 1, 2, 3, 4, 5, mmoetiy, 7, 8 and 9, wherein R3, R4 and R5 are each and independently methyl under the proviso that one of R3, R4 and R5 is of the following formula 3: The conjugate of embodiment 82, 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 as defined herein.
In an embodiment of the conjugate of the invention the target to which the further targeting moiety of the conjugate of the invention is capable of binding, is selected from group B as defined herein.
As preferably used herein low density means that less than copies of NTR per cell are expressed. First of all the amide linkage of this can be formed to a carboxylic acid group of moiety in solution example 8 mostiy 9 without the need for isolated activated carboxylic groups.
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The conjugate of embodiment 46, wherein the adapter moiety AD3 mediates the linkage between branching moiety [Y] and the effector moiety EM. MoL Imaging,30, ; and Janssen et al. Primary or secondary amino, carboxylic acid, activated carboxylic acid, chloro, bromo, iodo, sulfhydryl, hydroxyl, sulfonic acid, activated sulfonic acid, sulfonic acid esters like mesylate or tosylate, Michael acceptors, strained alkenes like trans cyclooctene, isocyanate, isothiocyanate, aldehyde, ketone, aminooxy, hydrazide, hydrazine, azide, alkyne and tetrazine.