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.
|Published (Last):||8 June 2016|
|PDF File Size:||11.25 Mb|
|ePub File Size:||19.25 Mb|
|Price:||Free* [*Free Regsitration Required]|
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. Molecular and Biomolecular Spectroscopyvol.
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.
It will be appreciated by a person skilled in the art that depending on the structural class and origin of the targeting moiety different types of reactive groups are provided by the targeting molecule.
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.
The lipid membrane that surrounds the cell favors the passage of only lipid soluble materials which is an important condition for antimicrobial activity.
Phenanthroline – Wikipedia
In another embodiment of the conjugate of the invention the conjugate comprises, in terms of an adapter moiety, a second adapter moiety AD2 only. Selected synthetic precursors for the adapter moieties for this application are in either commercially available and also referred to as cross-linkers, or can be prepared by a person phenamthroline in the art by routine measure.
Phenanthrolime Wikipedia, the free encyclopedia. These NTR1 expressing tumor indications include but are not limited to 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.
It is a white solid that is soluble in organic solvents. View at Google Scholar F.
Bioinorganic Chemistry and Applications
The above finding is insofar even more surprising as the conjugate of the invention comprises a second targeting moiety, whereby such second targeting moiety does not interfere with the binding characteristics of the first targeting moiety.
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 the first targeting moiety TM1 or by the second targeting moiety TM2. In an embodiment and as preferably used herein, C 3 -C 8 cycloalkylmethyl means each and individually any of cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl and cyclooctylmethyl.
A slight positive phenxnthroline of purified nitrogen was maintained in the titration cell in order to exclude oxygen and carbon dioxide from the reaction solutions. More preferably such discrimination or distinction forms the basis for said diagnosis and diagnosing, respectively. The values of and the response slopes from the potentiometric titrations were measured by fitting a straight line through the experimental points collected from pH 1.
It complrxes be appreciated by a person skilled in the art that the target recognized by the further targeting moiety, regardless of whether it is within the conjugate of the invention the first targeting moiety TM1 or the second targeting moiety TM2, can, in principle, be any target under the proviso that the further targeting moiety is capable of binding to such target. A “Michael acceptor” is capable of reacting with nucleophiles especially sulfhydryl groups in an addition reaction as exem phenanyhroline as follows: Neurotensin is bound by neurotensin receptors.
This adapter moiety enables complexrs conjugation of sulfhydryl containing moieties as shown in example As shown in Figure 5the species is major species found in an aqueous solution at pH 4. Agonists and antagonists binding to NTR1 have been described in the prior art. Building block moiety macocyclic aif present, is linked to both of its neighbours by a linkage, wherein the linkage is selected from the group comprising an amide linkage, a urea linkage, a carbamate linkage, an ester linkage, an ether linkage, a thioether linkage and a disulfide linkage.
The neurotensin receptor 1 NTRl pjenanthroline cloned in from rat brain and found to act as a high affinity, levocabastine insensitive receptor for neurotensin Tanaka et al, Neuron,4, Based on this, synthesis of different coordination compounds with desired properties by ligand tailoring has become a fascinating research field.
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.
Study of Metal-1,Phenanthroline Complex Equilibria by Potentiometric Measurements
The receptor can also stimulate cAMP formation, MAP kinase activation and the induction of growth related genes, such as krox Vincent et al. The conjugate of any one of embodiments 1, 2, 3, 4, 5 and 6, preferably any one of complexss 1 and 2, wherein R is isopropyl. Binding and pharmacological studies demonstrate that this receptor binds neurotensin as well as several other ligands already described for NTRl.
While coordinating, the properties of the ligands themselves are also modified. In an embodiment and as preferably used herein, a therapeutic agent or a therapeutically active agent is a compound which is suitable marcocyclic or useful in the treatment of a disease. The Selectivity factor is the quotient of target dissociation constant and anti-target dissociation constant.
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 moettiy, a hydrazone, a disulfide linkage, a pyrazine linkage and a dihydro-pyrazine linkage.
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.