1011-50-3Relevant academic research and scientific papers
Chemoselective Cleavage of Si-C(sp3) Bonds in Unactivated Tetraalkylsilanes Using Iodine Tris(trifluoroacetate)
Matsuoka, Keitaro,Komami, Narumi,Kojima, Masahiro,Mita, Tsuyoshi,Suzuki, Kimichi,Maeda, Satoshi,Yoshino, Tatsuhiko,Matsunaga, Shigeki
supporting information, p. 103 - 108 (2021/01/13)
Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp3) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp3) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). The reaction proceeds smoothly under mild conditions (-50 °C to room temperature) and tolerates various polar functional groups, thus enabling subsequent Tamao-Fleming oxidation to provide the corresponding alcohols. NMR experiments and density functional theory calculations on the reaction indicate that the transfer of alkyl groups from Si to the I(III) center and the formation of the Si-O bond proceed concertedly to afford an alkyl-λ3-iodane and silyl trifluoroacetate. The developed method enables the use of unactivated tetraalkylsilanes as highly stable synthetic precursors.
NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
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, (2014/09/29)
The present invention relates to compounds of the formula (I), the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof. In formula I the variables Het, A, X, Y, Z, R1, R2, R3, R4, R5 and Q are as defined in the claims. The compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof are inhibitors of phosphodiesterase type 10A. Thus, the invention also relates to the use of the compounds of the formula I, the N-oxides, tautomers, the prodrugs and the pharmaceutically acceptable salts thereof for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.
NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
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, (2013/02/28)
The present invention relates to novel carboxamide compounds, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating or controlling medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders
Direct aminoalkylation of arenes, heteroarenes, and alkenes via Ni-catalyzed Negishi cross-coupling reactions
Melzig, Laurin,Dennenwaldt, Teresa,Gavryushin, Andrey,Knochel, Paul
experimental part, p. 8891 - 8906 (2011/12/15)
A room-temperature Ni-catalyzed cross-coupling of aryl, heteroaryl, and alkenyl electrophiles with aminoalkylzinc bromides, readily available from the corresponding aminoalkyl chlorides via Grignard reagents, was developed. The reaction allows a convenient one-step preparation of various aminoalkyl products, including piperidine and tropane derivatives. Such functionalized amine moieties are widely present in various biologically active molecules. Aryl, heteroaryl, and alkenyl iodides, bromides, chlorides and triflates are suitable electrophiles. A short total synthesis of two natural products, (±)-galipinine and (±)-cusparine, is also reported.
Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia
Helal, Christopher J.,Kang, Zhijun,Hou, Xinjun,Pandit, Jayvardhan,Chappie, Thomas A.,Humphrey, John M.,Marr, Eric S.,Fennell, Kimberly F.,Chenard, Lois K.,Fox, Carol,Schmidt, Christopher J.,Williams, Robert D.,Chapin, Douglas S.,Siuciak, Judith,Lebel, Lorraine,Menniti, Frank,Cianfrogna, Julia,Fonseca, Kari R.,Nelson, Frederick R.,O Connor, Rebecca,MacDougall, Mary,McDowell, Laura,Liras, Spiros
scheme or table, p. 4536 - 4547 (2011/09/16)
Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.
HETEROAROMATIC QUINOLINE-BASED COMPOUNDS
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Page/Page column 26, (2010/11/30)
The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to compounds which are selective inhibitors of PDE10. The invention further relates to intermediates for preparation of such compounds; pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders. The invention relates also to methods for treating neurodegenerative and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom.
