68887-65-0Relevant articles and documents
Preparation of tetrazine-containing [2 + 1] complexes of 99mTc and: In vivo targeting using bioorthogonal inverse electron demand Diels-Alder chemistry
Yazdani, Abdolreza,Janzen, Nancy,Czorny, Shannon,Ungard, Robert G.,Miladinovic, Tanya,Singh, Gurmit,Valliant, John F.
, p. 14691 - 14699 (2017)
The aim of this work was to synthesize and evaluate [2 + 1] 99mTc(i) polypyridine complexes containing tetrazines, which along with the corresponding Re(i) complexes, represent a new class of isostructural nuclear and turn-on luminescent probes that can be derivatized and targeted using bioorthogonal chemistry. To this end, [2 + 1] complexes of 99mTc(i) of the type [99mTc(CO)3(N^N)(L)] (N^N = bathophenanthroline disulfonate (BPS) or 2,2′-bipyridine (bipy)), where the monodentate ligand (L) was a tetrazine linked to the metal through an imidazole derivative, were prepared. The desired products were obtained in nearly quantitative radiochemical yield by adding [99mTc(CO)3(N^N)(OH2)]n to the imidazole-tetrazine ligand and heating at 60 °C for 30 min. Measurement of the reaction kinetics between the tetrazine and (E)-cyclooct-4-enol revealed a second-order rate constant of 8.6 × 103 M-1 s-1 at 37 °C, which is suitable for in vivo applications that require rapid coupling. Stability studies showed that the metal complexes were resistant to ligand challenge and exhibited reasonable protein binding in vitro. Biodistribution studies of the more water-soluble BPS derivative in normal mice, one hour after administration of a bisphosphonate derivative of trans-cyclooctene (TCO-BP), revealed high activity concentrations in the knee (9.3 ± 0.3 %ID g-1) and shoulder (5.3 ± 0.7 %ID g-1). Using the same pretargeting approach, SPECT/CT imaging showed that the [2 + 1] tetrazine complex localized to implanted skeletal tumors. This is the first report of the preparation of 99mTc complexes of BPS and demonstration that their tetrazine derivatives can be used to prepare targeted imaging probes by employing bioorthogonal chemistry.
Imidazole heterocyclic diphosphonic acid compound as well as preparation method and application thereof
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Paragraph 0110; 0111, (2017/07/20)
The invention belongs to the field of pharmaceutical chemistry, and in particular relates to an imidazole heterocyclic diphosphonic acid compound as well as a preparation method and application thereof. The imidazole heterocyclic diphosphonic acid compound has a larger non-toxic concentration range for an osteoclast precursor, and can significantly inhibit the formation of osteoclasts at the same time; the imidazole heterocyclic diphosphonic acid compound can damage actin ring to the utmost extent, thus having an obvious inhibiting effect on the osteoclasts and further being used as an osteoclast inhibitor; the imidazole heterocyclic diphosphonic acid compound solves the problems that diphosphonate in the prior art is low in inhibiting effect on the osteoclasts, high in toxicity and large in side effects.
Bicyclic Pyrimidine Compounds
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Paragraph 0109; 0110; 0111, (2014/07/23)
The present invention provides compounds of the Formula I: wherein X is a bond or CH2; R is selected from the group consisting of R1 and R2 are each independently selected from the group consisting of CH and N; R3 is H or CH3; R4 is H or CH3; L is selected from the group consisting of —O(CH2)3—, —C(O)NH(CH2)2—, —CH2C(O)NH(CH2)2—, —(CH2)3N(C(O)CH3)CH2—, —(CH2)2N(C(O)CH3)CH2—, —(CH2)3NH—, (CH2)2OCH2—, —(CH2)4—, —(CH2)2NHCH2—, —(CH2)3O—, and —CH2O(CH2)2—; or a pharmaceutically acceptable salt thereof. Compounds of this invention are autotaxin inhibitors.
