- Accessing Difluoromethylated and Trifluoromethylated cis-Cycloalkanes and Saturated Heterocycles: Preferential Hydrogen Addition to the Substitution Sites for Dearomatization
-
Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis-difluoromethylated and cis-trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all-cis multi-trifluoromethylated cyclic products with a defined equatorial orientation of the di- and trifluoromethyl groups. Deuterium-labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites.
- Zhang, Xue,Ling, Liang,Luo, Meiming,Zeng, Xiaoming
-
-
Read Online
- Metallaphotoredox Difluoromethylation of Aryl Bromides
-
Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl-radical-mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late-stage functionalization of several drug analogues.
- Bacauanu, Vlad,Cardinal, Sébastien,Yamauchi, Motoshi,Kondo, Masaru,Fernández, David F.,Remy, Richard,MacMillan, David W. C.
-
supporting information
p. 12543 - 12548
(2018/09/18)
-
- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
-
Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
- -
-
Paragraph 0738; 0739
(2017/04/04)
-
- Silver-Mediated 18F-Labeling of Aryl-CF3 and Aryl-CHF2 with 18F-Fluoride
-
We report the synthesis of [18F]arylCF3 and [18F]arylCHF2 derivatives from arylCF2Br and arylCHFCl precursors applying a silver-mediated halogen exchange with [18F]fluoride. In the absence of Ag(I)OTf, no reaction takes place at room temperature for both classes of substrates; this result demonstrates the beneficial role of silver(I) as a means to induce 18F-incorporation under very mild conditions.
- Verhoog, Stefan,Pfeifer, Lukas,Khotavivattana, Tanatorn,Calderwood, Samuel,Collier, Thomas Lee,Wheelhouse, Katherine,Tredwell, Matthew,Gouverneur, Véronique
-
supporting information
p. 25 - 28
(2015/12/26)
-
- PYRROLOTRIAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrrolotriazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 44
(2016/09/26)
-
- PYRAZOLOPYRIMIDINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrazolopyrimidine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 66
(2016/09/26)
-
- THIENOPYRAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to thienopyrazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 39
(2016/09/26)
-
- PYRROLOPYRIDAZINE INHIBITORS OF IRAK4 ACTIVITY
-
The present invention relates to pyrrolopyridazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
- -
-
Page/Page column 43
(2016/09/26)
-
- Silver-catalyzed oxidative activation of benzylic C-H bonds for the synthesis of difluoromethylated arenes
-
A mild and catalytic method to form difluoromethylated arenes through the activation of benzylic C-H bonds has been developed. Utilizing AgNO3 as the catalyst, various arenes with diverse functional groups undergo activation/fluorination of ben
- Xu, Peng,Guo, Shuo,Wang, Liyan,Tang, Pingping
-
supporting information
p. 5955 - 5958
(2014/06/10)
-
- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
-
Provided herein are novel substituted bicyclic aza-heterocycle sirtuin- modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin- modulating compound in combination with another therapeutic agent.
- -
-
Page/Page column 190
(2013/05/09)
-
- C-ARYL GLYCOSIDE COMPOUNDS FOR THE TREATMENT OF DIABETES AND OBESITY
-
This invention relates to a compound of generic formula (I): (I) as well as a pharmaceutically acceptable salt thereof, a tautomer, optical isomer or a mixture of optical isomers in any proportion, in particular a mixture of enantiomers, and particularly a racemate mixture, in particular for use thereof as a drug, notably in the treatment of diabetes.
- -
-
Page/Page column 60-61
(2009/10/30)
-
- PYRIDO [4,3-d] PYRIMIDIN-4 (3H) -ONE DERIVATIVES AS CALCIUM RECEPTOR ANTAGONISTS
-
The present invention is directed to novel pyrido[4,3-d]pyrimidin-4(3H)-one derivatives and pharmaceutically acceptable salts thereof of structural formula I wherein the variables R1, R2, R3, R4 and R5 are as described herein. Also provided are pharmaceutical compositions comprising the compounds of formula I as well as methods of treatment employing compounds of formula I to treat a disease or disorder characterized by abnormal bone or mineral homeostasis such as hypoparathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, bone fracture, osteoarthritis, rheumatoid arthritis, and humoral hypercalcemia of malignancy.
- -
-
Page/Page column 21
(2008/06/13)
-
