86259-87-2Relevant academic research and scientific papers
Naloxegol Oxalate and Solid Dispersion thereof
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Paragraph 0126, (2021/11/05)
The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.
Effects of 18F-fluorinated neopentyl glycol side-chain on the biological characteristics of stilbene amyloid-β PET ligands
Tago, Tetsuro,Toyohara, Jun,Fujimaki, Ryo,Tatsuta, Maho,Song, Ruichong,Hirano, Keiichi,Iwai, Kumiko,Tanaka, Hiroshi
, p. 38 - 45 (2021/01/26)
Introduction: The 2,2-dihydroxymethyl-1-[18F]fluoropropane group, also called 18F-labelled neopentyl glycol side-chain, is a novel 18F-labelling group for positron emission tomography (PET) imaging agents. The aim of using this group is to develop simple purification with solid-phase extraction without high-performance liquid chromatography. However, the effects of the neopentyl 18F-labelling group on the characteristics of brain imaging agents are unknown. Here, we added this side-chain to compounds with an aminostilbene structure to evaluate their effects on the biological properties of aminostilbene as an amyloid-β (Aβ) radioligand. Methods: Biodistributions of four novel 18F-labelled stilbene compounds with different lengths of polyethylene glycol (PEG) linkers, called [18F]Cpd-0, -1, -2, and -4, (PEG = 0, 1, 2, and 4), and [18F]AV-1 in normal mice were evaluated. Metabolite analysis of [18F]Cpd-0 and -1 was performed with mouse plasma and brain. A competitive binding assay of [18F]AV-1 binding to Aβ1–42 fibrils was performed to determine the binding properties of the compounds. Results: [18F]Cpd-0, -1, and -2 demonstrated moderate initial brain uptake in mice (3.1–4.2% injected dose/g at 2 min post-injection) followed by fast clearance, and in vivo defluorination of these compounds was negligible. [18F]Cpd-4 exhibited low brain uptake and high bone uptake. Compared with [18F]Cpd-1, the percentage of [18F]Cpd-0 in mouse brain was high at 10 min post-injection. A competitive binding assay revealed partial interference effects by the neopentyl glycol side-chain on binding of stilbene compounds to Aβ1–42 fibrils. Conclusions: Aminostilbene compounds with two or fewer PEG linkers containing an 18F-labelled neopentyl glycol side-chain demonstrated preferable pharmacokinetic properties as a brain imaging radioligand in normal mice. These side-chains can be used as an alternative labelling group for imaging agents targeting the brain.
Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
supporting information, (2020/07/21)
The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
PROTEOLYSIS-TARGETING PROTACS INDUCING DEGRADATION OF C-MIC PROTEIN
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Page/Page column 00205-00206; 00209-00210, (2020/12/30)
Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (MC-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (ME3). AS such, the disclosed PROTACS may be described as having a formula Mc-MYC-L-ME3 or ME3-L-Mc-MYC.
SUPRAMOLECULAR PROTEIN ASSEMBLIES WITH ADVANCED FUNCTIONS AND SYNTHESIS THEREOF
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Paragraph 0462-0463, (2019/05/18)
The present invention discloses stimuli-sensitive protein conjugate which can make supramolecular protein assemblies and methods for using the same. The present invention provides simple and rational process for construction of said stimuli-sensitive spherical protein assemblies through supramolecular chemical strategy.
IRAK DEGRADERS AND USES THEREOF
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Paragraph 1988; 1989, (2019/07/10)
The present invention provides compounds, compositions thereof, and methods of using the same.
NALOXEGOL OXALATE AND SOLID DISPERSION THEREOF
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Paragraph 24; 25, (2018/06/12)
The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.
Templated Formation of Luminescent Virus-like Particles by Tailor-Made Pt(II) Amphiphiles
Sinn, Stephan,Yang, Liulin,Biedermann, Frank,Wang, Di,Kübel, Christian,Cornelissen, Jeroen J. L. M.,De Cola, Luisa
supporting information, p. 2355 - 2362 (2018/02/19)
Virus-like particles (VLPs) have been created from luminescent Pt(II) complex amphiphiles, able to form supramolecular structures in water solutions, that can be encapsulated or act as templates of cowpea chlorotic mottle virus capsid proteins. By virtue
EGFR PROTEOLYSIS TARGETING CHIMERIC MOLECULES AND ASSOCIATED METHODS OF USE
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Paragraph 00661; 00662, (2018/07/29)
The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of the target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
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Paragraph 1451, (2018/05/24)
The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
