24811-78-7Relevant academic research and scientific papers
TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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Paragraph 1160; 1161, (2021/02/12)
The present disclosure relates to bifunctional compounds, which find utility as modulators of tan 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 tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.
MRGX Receptor Antagonists
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, (2021/05/07)
The invention relates to a method for preventing or treating a disease or disorder that is associated with the MrgX2 receptor. The invention also relates to MrgX2 antagonists and physiologically acceptable salts thereof. The invention also relates to pharmaceutical compositions and dosage forms comprising an MrgX2 antagonist.
Practical Synthesis of a Stable Precursor for Positron Emission Tomography Imaging Agent 18F-GTP1
Clagg, Kyle,Gosselin, Francis,Lim, Ngiap-Kie,Nack, William A.,O'Shea, Paul D.,Sirois, Lauren E.,White, Nicholas A.,Zhang, Haiming
, p. 1690 - 1699 (2020/11/25)
18F-GTP1 is a deuterated small molecule positron emission tomography (PET) imaging agent used to visualize tau tangles in Alzheimer's disease patients. The first-generation synthesis of 18F-GTP1's nonradiolabeled alkyl tosylate precursor was plagued by low-yielding steps, inefficient chromatographic purifications, and variable product quality. Due to these limitations, a more robust second-generation route was developed and successfully executed on kilogram scale. A reduction with LiAlD4 incorporated geminal deuterium atoms, while an efficient amidation reaction accessed the key acrylamide coupling partner. Moreover, the tricyclic imidazo[1,2-a]pyrimidine core was assembled via a novel, convergent, and highly selective phosphoramidate-directed annulation. The improved synthesis eliminated all chromatography en route to a high-yielding and reproducible acid-promoted tosylation as the final step.
TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
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Paragraph 1444; 1445, (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.
For detecting imaging agent of neurological disorders
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, (2016/10/08)
Imaging agents of formulas (I)-(V) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formulas (I)-(V) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formulas (I)-(V) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.
DEUTERATED HETEROCYCLIC COMPOUNDS AND THEIR USE AS IMAGING AGENTS
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, (2016/01/22)
The present invention relates to deuterated and optionally detectably labeled compounds of formula (I): R1-A-R2 and formula (V) and salts thereof, wherein Rl, R2, A, and X10-X19 have any of
Concise and high-yield synthesis of T808 and T808P for radiosynthesis of [18F]-T808, a PET tau tracer for Alzheimer's disease
Gao, Mingzhang,Wang, Min,Zheng, Qi-Huang
, p. 254 - 257 (2014/01/17)
The authentic standard T808 and its corresponding mesylate precursor T808P were synthesized in six steps using ethyl vinyl ether and trichlorocetyl chloride as starting materials. The overall chemical yields of T808 and T808P were 35% and 52%, respectively. [18F]-T808 was synthesized from T808P by the nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC combined with solid-phase extraction (SPE) purification in 35-45% radiochemical yield with 37-370 GBq/μmol specific activity at end of bombardment (EOB).
Synthesis and characterization of some novel 2-(trifluoromethyl)pyrimido- [1,2-a]benzimidazoles and pyrimido[1,2-a]benzimidazol-2H-ones of biological interest
Zanatta, Nilo,Amaral, Simone S.,Esteves-Souza, Andressa,Echevarria, Aurea,Brondani, Patricia B.,Flores, Darlene C.,Bonacorso, Helio G.,Flores, Alex F. C.,Martins, Marcos A. P.
, p. 2305 - 2312 (2008/02/02)
The synthesis of some potentially active 2-(trifluoromethyl)pyrimido [1,2-a]benzimidazoles and pyrimido[1,2-a]benzimidazol-2(1H)-ones by the cyclization of 4-alkoxyvinyl trifluoro(chloro)methyl ketones with 2-aminobenzimidazole is described. The structure
