1,Phenanthroline forms a stable complex with Fe(II) ion called ferroin, which is used as an indicator in Fe(II) salt titrations. Ferroin is also. Structure, properties, spectra, suppliers and links for: phenanthroline, 1,Phenanthroline [ACD/Index Name] [ACD/IUPAC Name]. preferably any one of embodiments 1, 2 and 10, wherein ALK and ALK’ are both propylene, moetiy is typically an antagonist; if under such conditions the second targeting moiety is Tris(4,7-diphenyl- 1,phenanthroline)ruthenium( II).
The conjugate of any one of embodiments 1 to 59, wherein one of the first targeting moiety TM1 and the second targeting moiety TM2 is selected from the group comprising an antibody, an antigen-binding antibody fragment, a camelid heavy phenznthroline IgG hcIgGa cartilaginous fish IgNAR antibody, a protein scaffold, a target-binding peptide, a peptide nucleic acid PNAa target-binding polypeptide or protein, a target binding nucleic acid molecule, a carbohydrate, a lipid and a target-binding small molecule.
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.
As preferably used herein, the term “activated sulfonic acid” refers to a sulfonic acid group with the general formula -S0 2 -X, wherein X is a leaving group. 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 in an indication, preferably a tumor indication, in which only a small portion of the tumors, preferably a tumor indication where only a small portion of the patients suffering from the tumor indication, express NTR1.
phenanthroline | C12H8N2 | ChemSpider
The preparation mostiy 56 is described in Example 5A. For example, in case the first targeting moiety is targeting NTR1 the first targeting moetiy is typically an antagonist; if under such conditions phenanthrooine second targeting moiety is targeting a second target which, in an embodiment, is different from NTR1 or which, in an alternative embodiment is NTR1, and such second targeting moiety also acts as an antagonist of such second target, the conjugate of the invention is typically regarded as an antagonist; if, however, the second targeting moiety is targeting a second target which, in an embodiment, is different from NTR1 or which, in an alternative embodiment, is NTR1 and such second targeting moiety acts as an agonist of such second target, the conjugate of the invention inherently bears both the characterisitic of an antagonist and of an agonist.
Eptinezumab Erenumab Fremanezumab Galcanezumab. Such internalization phenanthrolind occurs by means of endycytosis. More preferably, a chemical bond is a covalent bond or a plurality of chemical bonds.
The conjugate of any one of embodiments 2 to 42, wherein the Effector moiety EM is linked, preferably covalently linked to the second targeting moiety TM2. In an embodiment the number of covalent bonds between the first targeting moiety TM1 and the second targeting moiety TM2 is 1. In an embodiment and as preferably used herein, a theragnostically active compound is a compound which is suitable for or useful in both the diagnosis and phennathroline of a disease.
It is understood by a person skilled in the art that several different technical and mechanistical alternatives exist to realize a specific type of linkage, for instance an amide bond. It will, however, be understood by a person skilled in the art that neither the linkages which may be realized in embodiments the conjugate of the invention are limited to the ones of Table 4 nor the reactive groups forming such linkages.
The conjugate of embodiment 93, wherein the disease is a disease involving a target targeted by the first targeting moiety TM1 or by the second targeting moiety TM2, preferably the disease is one involving neurotensin receptor, preferably the disease is a disease involving neurotensin receptor 1. Therefore, an optimal compound and even more so a radiolabeled version thereof suitable for diagnosis and therapy, respectively, of a disease is a matter of luck rather than of a rational and predictable development process.
Conventional amino acids, also referred to as natural amino acids are identified according to their standard, one-letter or three-letter codes, as set forth in Table 1. In a further embodiment of the conjugate of the invention an adapter moiety is one of. It will be appreciated by a person skilled in the art that the linking of a moiety comprising an isothiocyanate with a phenantholine comprising a primary or secondary amino leads to a linkage named thiourea phenantbroline is also referred to as a thiourea linkage, -N-CS-N-and linking of a moiety comprising a halogen atom with a moiety comprising a sulfhydryl -SH leads to thioether which is also referred to as a thioether linkage, -S.
Inserted into a conjugate of the invention an adaptor moiety as preferably used moeyiy the conjugate of the invention is one which is indicated in the following formulae, whereby it is understood that to the extent the adapter moiety is represented in the formulae as being inserted between linking moiety LM and targeting moiety TM2 thus being a second adapter moiety, this is made for purpose of illustration only and the adapter moiety as such is the structure contained in square phenanthrolinw.
R 6 is selected from the group consisting of hydrogen and Ci-C 4 alkyl; and. For example, a capital first letter indicates that the L-form of the amino acid is present in the peptide sequence, while a lower case first letter indicating that the D-form of the correspondent amino acid is present in the peptide sequence.
R 3R 4 and R 5 are each and independently selected from the group consisting of hydrogen and methyl under the proviso that one of R 3R 4 and R 5 is of the following formula 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.
In other words, the first reactive group can be provided by either the first moiety or the second moiety under the proviso that the second reactive group is either provided by the second moiety or the first moiety, so that in each case the necessary reactive groups are present or are formed, respectively, allowing the forming of the linkage.
R 6 is selected from the group consisting of hydrogen and methyl; and.
It is understood that both modifications can apply to the same amino acid and apply to adjacent conventional amino acids present in amino acid sequences without hyphens explicitly illustrated.
It was found that moeyiy neurotensin-derived metal labeled peptides have a very short circulation half-life due to rapid renal clearance as often observed for peptidic molecules.
O-Phenanthroline | C12H8N2 – PubChem
The conjugate of any one of embodiments 20 and 21wherein the first targeting moiety is a compound of formula 4. In another embodiment of the conjugate of the invention the conjugate comprises, in terms of an adapter moiety, a third adapter moiety AD3 phenanthroine.
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 Fe, 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.
US discloses a synthetic tridecapeptide [Gln 4 ]-neurotensin having hormonal activity. TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target. From Wikipedia, the free encyclopedia. The conjugate of embodiment 76, wherein the glycoside is a N- glycoside, C-glycoside, O-gylcoside or an S-glycoside, preferably the glycoside is N- glycoside. Imaging,30, ; and Janssen et ah, Cancer Biother. In light of these surprising characteristics it is possible that, without wishing to be bound by any theory, because of the two targeting moieties more patients can be positively diagnosed and treated, respectively, within an indication.
Neurotensin Neuromedin N Antagonists: One example for this is the attachment of a maleimide containing adapter moiety is described in example 5B:.
Phenanthroline phen is a heterocyclic organic compound. The preferred type of adapter moieties in one embodiment are dicarboxylic acids, or activated forms thereof.