178369-93-2Relevant academic research and scientific papers
Air-Stable PdI Dimer Enabled Remote Functionalization: Access to Fluorinated 1,1-Diaryl Alkanes with Unprecedented Speed
Kundu, Gourab,Opincal, Filip,Schoenebeck, Franziska,Sperger, Theresa
, (2021/11/30)
While remote functionalization via chain walking has the potential to enable access to molecules via novel disconnections, such processes require relatively long reaction times and can be in need of elevated temperatures. This work features a remote arylation in less than 10 min reaction time at room temperature over a distance of up to 11 carbons. The unprecedented speed is enabled by the air-stable PdI dimer [Pd(μ-I)(PCy2tBu)]2, which in contrast to its PtBu3 counterpart does not trigger direct coupling at the initiation site, but regioconvergent and chemoselective remote functionalization to yield valuable fluorinated 1,1-diaryl alkanes. Our combined experimental and computational studies rationalize the origins of switchability, which are primarily due to differences in dispersion interactions.
B(C6F5)3-Catalyzed Diastereoselective Formal (4 + 1)-Cycloaddition of Vinylcyclopropanes and Et2SiH2
Long, Peng-Wei,Oestreich, Martin
supporting information, p. 4834 - 4837 (2021/06/28)
A formal (4 + 1)-cycloaddition of vinylcyclopropanes and Et2SiH2 to afford 3,4-disubstituted silolanes is reported. The reaction sequence commences with the known B(C6F5)3-catalyzed alkene hydrosilylation with dihydrosilanes. Cleavage of the remaining Si-H bond in the hydrosilylation product assisted by B(C6F5)3 leads to formation of a cyclopropane-stabilized silylium ion. The activated cyclopropane ring is then opened by the in situ-generated borohydride accompanied by ring closure to the silolane. The diastereoselectivity is rationalized by a mechanistic model.
Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
Yamashita, Yasunobu,Tanaka, Ken-ichiro,Yamakawa,Asano,Kanda, Yuki,Takafuji,Kawahara, Masahiro,Takenaga, Mitsuko,Fukunishi, Yoshifumi,Mizushima
, p. 3339 - 3346 (2019/06/18)
The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.
SYNTHESIS AND UTILIZATION OF SMALL MOLECULES FOR THE TREATMENT OF INFLAMMATION ASSOCIATED WITH INTERLEUKIN-1 SIGNALING
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Page/Page column 11-12; 2/2, (2010/04/03)
The invention describes synthetic compounds, methods of preparation and their uses thereof an anti-inflammatory compounds that reduce inflammation associated with interleukin-1signaling.
AMINE COMPOUND AND PHARMACEUTICAL USE THEREOF
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Page/Page column 48, (2010/04/25)
Provided is a novel amine compound represented by the following formula (I) having a superior peripheral blood lymphocyte decreasing action and superior in the immunosuppressive action, rejection suppressive action and the like, which shows decreased side effects of, for example, bradycardia and the like, or a pharmaceutically acceptable acid addition salt thereof, or a hydrate thereof, or a solvate thereof. wherein each symbol is as defined in the specification.
Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects
Hamilton, Gregory S.,Wu, Yong-Qian,Limburg, David C.,Wilkinson, Douglas E.,Vaal, Mark J.,Li, Jia-He,Thomas, Christine,Huang, Wei,Sauer, Hansjorg,Ross, Douglas T.,Soni, Raj,Chen, Yi,Guo, Hongshi,Howorth, Pamela,Valentine, Heather,Liang, Shi,Spicer, Dawn,Fuller, Mike,Steiner, Joseph P.
, p. 3549 - 3557 (2007/10/03)
The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.
