10 PHENANTHROLINE MOETIY PDF
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).
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R 3R 4 and R 5 are each and independently selected from the group consisting of hydrogen and C! 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 the group comprising Alpha v beta 3 integrin Kumar, Curr Drug Targets,4, ; Danhier et al, Mol Pharm,9,Alpha v beta 6 integrin Bandyopadhyay et al, Curr Drug Targets,Hausner et al, Cancer Res,Amino acid transporter L Haase et al, J Nucl Med,48, ; Imai et al, Anticancer Res,30,Atrial natriuretic peptide receptor 1 Wang et al, Mol Cancer,10, 56; Kong et al.
Lin 2if present, and Lin 3if present, are each individually and independently selected from the group comprising -CO- -NR. The receptor is also expressed in the dorsal root ganglion neurones of the spinal cord. The conjugate of embodiment 8, wherein R 6 is selected from the group consisting of hydrogen and methyl.
Additionally, it is thus possible to diagnose and treat, respectively, tumors expressing afirst target with low density, such as, for example copies of the target or less per tumor cell while said tumors express any number of copies of a second target targeted by a conjugate of the invention. 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.
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 therapy of a disease. The conjugate of any one of embodiments 93 to 99, wherein Effector is a radionuclide, wherein preferably the radionuclide is covalently bound by Acceptor, wherein Acceptor comprises an aromatic moiety, wherein the aromatic moiety is selected from the group comprising indole and benzene, preferably benzene is substituted with at least one heteroatom, wherein the heteroatom is selected from the group comprising O, N and S.
The conjugate of any one 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. The conjugate of any one of embodiments 1, 2, 3, 4, 5 and 6, preferably any one of embodiments 1 and 2, wherein R is isopropyl.
Apart from the central nervous system, NTR1 is highly expressed in a mammalian body and a human body in particular on several neoplastic cells in several tumor indications, whereas the expression of NTR1 in most other tissues of the mammalian and the human body is either not existent or low.
For non-conventional amino acids, a 3 -letter code was used where the first letter indicates the stereochemistry of the C-a-atom. S45S60S It is within the present invention that the conjugate of the invention comprises, under the proviso that either the first targeting moiety TMl or the second targeting moiety TM2 is a compound of formula 2in any of its embodiments, a further targeting moiety.
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. 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 in an oncology indication, more preferably in any indication related to oncology, where NTR is expressed in the primary tumor, in metastases, preferably metastases of the primary tumor, or in both the primary tumor and metastates, preferably metastases of the primary tumor.
More preferably such discrimination or distinction forms the basis for said diagnosis and diagnosing, respectively. The very same structure depicted as a second adapter moiety can, in accordance with the instant invention, phnanthroline equally used as a first targeting moiet:. Dermatol, Because of this, the other moieties attached to the compound of formula 2 in moetiu conjugate of the invention phdnanthroline vary in a broad manner as is further supported by pphenanthroline example part.
US discloses neurotensin mimetics as central nervous system agents. Signal intensities are typically measured with a region-of-interest ROI analysis of the tumor and ROI analysis of surrounding healthy tissue as background see Palmedo et al, Nucl Med Biol,29, Many homoleptic complexes are known. R 6 is selected from the group consisting of hydrogen and C 1 -C alkyl; and. In an embodiment of the conjugate of the invention the further targeting moiety is preferably selected from the group comprising an antibody Book: The conjugate of any one of embodiments 93 to 94, wherein the disease is selected from the group comprising tumors and hematological malignancies.
A generic formula of a preferred embodiment of an adapter moiety is as follows:. It will be appreciated by a person skilled in the art that adapter moiety as subject to formulae 38 and 39 and the linkages indicated therein are preferably the result of, on the one hand of a primary or secondary amino group, preferably provided by a targeting moiety, phenantheoline, on the other hand, of a reactive group selected from the group comprising carboxylic acid, activated carboxylic acid, sulfonic acid, activated phenannthroline acid, isocyanates and isothiocyanates, wherein the reactive group is preferably provided by an adapter moiety.
R 2 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 3 – Cg cycloalkylmethyl, halogen, nitro and trifluoromethyl. In the periphery, neurotensin is found in endocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction Friry et al. In one embodiment the alkylamine linkage is formed by reacting a moiety comprising a primary or secondary amino group with a moiety comprising an aldehyde group or a ketone group either under reductive conditions or followed by subsequent reduction.
Imaging,36, ; Bergmann et al, Nucl. The conjugate of any one of embodiments towherein the disease is selected from the group comprising tumors and hematological malignancies.
The conjugate of any one of embodiments 1 to 70, wherein the second targeting moiety is selected from the group comprising an antibody, an antigen-binding antibody fragment, a camelid heavy chain IgG hcIgGa cartilaginous fish IgNAR antibody, a protein scaffold, a target-binding peptide, a peptide nucleic phensnthroline PNAa target-binding polypeptide or protein, a target binding nucleic acid molecule, a carbohydrate, a lipid and a target-binding small molecule.
The following is, in principle, applicable to each and any of the adapter moieties which can be realized in the various embodiments of the conjugate of the invention, i. Carcinomatosis; Epithelioma, benign; Epithelioma, malignant; Large cell carcinoma.
Such separation can be expressed by the number of covalent linkages realized between the first targeting moiety TM1 and the second targeting moiety TM2. 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. Fagan and William A. The method of embodimentwherein the conjugate comprises a diagnostically active agent, whereby the agent is preferably a radionuclide.
The predominant response upon activation of the receptor by neurotensin is activation of phospholipase C, causing an increase in intracellular calcium levels.
Also in accordance with the function of an adapter moiety in a conjugate of the invention, the reactive group s borne or provided by the adaptor moiety are of importance. The formation of a ligand-protein complex C can be described by a two-state process.
In a further embodiment of the conjugate of the invention a compound of formula 2in any of its embodiments, is present in the conjugate of the invention as targeting moiety TM2. Also, it is possible that more lesions can be diagnosed and treated, respectively, per patient.
Methods for determining the selectvitity factor 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 Neubauer et al, J Med Chem,57, The conjugate of any one of embodiments 1 to 78, for use in a method for the diagnosis of a disease. In an embodiment of the conjugate of the invention the antibody is a polyclonal or monoclonal antibody. The conjugate of any one of embodiments 1 to 78, for use in a method for the treatment of a disease.
In another phdnanthroline 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. The conjugate of any one of embodiments mmoetiy to 91, wherein the method comprises the administration of a diagnostically effective amount of the compound to a subject, preferably to a mammal, wherein the mammal is selected from the group comprising man, companion animals, pets and livestock, more preferably the subject is selected from the group comprising man, dog, cat, horse and cow, and most preferably the subject is a human being.
O-Phenanthroline | C12H8N2 – PubChem
Biol,33, ; Garcia-Garayoa et al, Eur. Examples of reactive groups which, in some embodiments of the invention, are used in the forming of linkages which may be realized in embodiments the phhenanthroline of the invention are summarized in Table 4. In an embodiment of the conjugate of the invention the target to which the further targeting moiety of the conjugate phenanthrolline the phennanthroline is capable of binding, is selected from the group comprising Alpha v beta 3 integrin, Alpha 5 beta lAlpha v beta 6 integrin, Amino acid transporter ASC, Amino acid transporter L, Aminopeptidase N ANP, CD 13Angiopoietin-1 receptor, Atrial natriuretic peptide receptor 1, Atrial natriuretic peptide receptor 2, A-type amino acid transporter, Avidin, Bcr-Abl tyrosine kinase, Bombesin receptor, Bombesin receptor subtype-3, CA antigen, CA As well-known from molecular-pharmacologic investigations efficient internalization is usually provided predominantly by agonists Bodei et ah, J.
To the extent it is referred in the instant application to a range indicated by a lower integer phdnanthroline 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.