946427-03-8Relevant articles and documents
Crisaborole intermediate, preparation method and application of crisaborole intermediate in preparation of crisaborole
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, (2021/04/03)
The invention discloses a crisaborole intermediate, a preparation method and application of the crisaborole intermediate in preparation of crisaborole. The crisaborole intermediate has a structure asshown in a formula I in the specification. The preparation method comprises the following steps: carrying out Grignard reaction on a compound shown in a structural formula VI in an organic solvent A or carrying out exchange reaction with a metal Grignard reagent, and reacting with borate to obtain a compound shown in a structural formula V; reacting the obtained compound with the structural formula V with pinacol in an organic solvent B to obtain a compound with a structural formula IV; removing a protecting group from the compound shown in the structural formula IV in an organic solvent C toobtain a compound shown in a structural formula III; and carrying out a coupling reaction on the compound shown in the structural formula III and 4-halogenated cyanophenyl shown in the structural formula II in an organic solvent D under an alkaline condition to obtain the crisaborole intermediate shown in the structural formula I. The method effectively solves the problems of high production costand low product purity, and is suitable for industrial large-scale production.
Preparation of labeled aromatic amino acids: Via late-stage18F-fluorination of chiral nickel and copper complexes
Craig, Austin,Kolks, Niklas,Urusova, Elizaveta A.,Zischler, Johannes,Brugger, Melanie,Endepols, Heike,Neumaier, Bernd,Zlatopolskiy, Boris D.
supporting information, p. 9505 - 9508 (2020/09/03)
A general protocol for the preparation of 18F-labeled AAAs and α-methyl-AAAs applying alcohol-enhanced Cu-mediated radiofluorination of Bpin-substituted chiral complexes using Ni/Cu-BPX templates as double protecting groups is reported. The chiral auxiliaries are easily accessible from commercially available starting materials in a few synthetic steps. The versatility of the method was demonstrated by the high-yielding preparation of a series of [18F]F-AAAs and the successful implementation of the protocol into automated radiosynthesis modules. This journal is
BIARYL COMPOUNDS USEFUL AS IMMUNOMODULATORS
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Page/Page column 142; 144, (2018/03/25)
The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.
Alcohol-Enhanced Cu-Mediated Radiofluorination
Zischler, Johannes,Kolks, Niklas,Modemann, Daniel,Neumaier, Bernd,Zlatopolskiy, Boris D.
supporting information, p. 3251 - 3256 (2017/03/17)
The potential of many 18F-labeled (hetero)aromatics for applications in positron emission tomography remains underexplored because convenient procedures for their radiosynthesis are lacking. Consequently, simple methods to prepare radiofluorinated (hetero)arenes are highly sought after. Herein, we report the beneficial effect of primary and secondary alcohols on Cu-mediated 18F-labeling. This observation contradicts the assumption that such alcohols are inappropriate solvents for aromatic fluorination. Therefore, we developed a protocol for rapid radiolabeling of an extraordinarily broad scope of boronic and stannyl substrates under general reaction conditions. Notably, radiofluorinated indoles, phenols, and anilines were synthesized directly from the corresponding unprotected precursors. Furthermore, the novel method enabled the preparation of radiofluorinated tryptophans, [18F]F-DPA, [18F]DAA1106, 6-[18F]FDA, and 6-[18F]FDOPA.
BCR-ABL TYROSINE-KINASE LIGANDS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
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Paragraph 00804; 00813; 008014, (2015/07/23)
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. invivo) to form a multimer (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding sites on a Bcr-Abl tyrosine kinase.
Synthesis of substituted asymmetrical biphenyl amino esters as alpha helix mimetics
Williams, Anna B.,Hanson, Robert N.
experimental part, p. 5406 - 5414 (2012/09/08)
As part of our ongoing project to develop new molecular probes for estrogen receptor-alpha, we are exploring the utility of internally-substituted asymmetric biphenyls as a proteomimetic scaffold. In this study, we describe synthetic methods for preparing
An improved procedure for the synthesis of arylboronates by palladium-catalyzed coupling reaction of aryl halides and bis(pinacolato)diboron in polyethylene glycol
Lu, Jie,Guan, Zhong-Zhi,Gao, Jian-Wu,Zhang, Zhan-Hui
experimental part, p. 537 - 541 (2012/04/04)
A new protocol has been developed for the synthesis of arylboronates by a coupling reaction of aryl halides and bis(pinacolato)diboron using bis(triphenylphosphine)palladium dichloride/sodium acetate/polyethylene glycol 600 [Pd(PPh3)2Cl2/NaOAc/PEG 600] as an efficient catalytic system. Copyright
(3-oxo)pyridazin-4-ylurea derivatives as PDE4 inhibitors
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Page/Page column 38, (2010/07/03)
New (3-oxo)pyridazin-4-ylurea derivatives having the chemcial structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).
1, 7-NAPHTHYRIDINE DERIVATIVES AS P38 MAP KINASE INHIBITORS
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Page/Page column 59-60, (2008/06/13)
This invention is directed to new inhibitors of the p38 mitogen-activated protein kinas having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.