- Copper-catalyzed formal transfer hydrogenation/deuteration of aryl alkynes
-
A copper-catalyzed reduction of alkynes to alkanes and deuterated alkanes is described under transfer hydrogenation and transfer deuteration conditions. Commercially available alcohols and silanes are used interchangeably with their deuterated analogues as the hydrogen or deuterium sources. Transfer deuteration of terminal and internal aryl alkynes occurs with high levels of deuterium incorporation. Alkyne-containing complex natural product analogues undergo transfer hydrogenation and transfer deuteration selectively, in high yield. Mechanistic experiments support the reaction occurring through a cis-alkene intermediate and demonstrate the possibility for a regioselective alkyne transfer hydrodeuteration reaction.
- Sloane, Samantha E.,Reyes, Albert,Vang, Zoua Pa,Li, Lingzi,Behlow, Kiera T.,Clark, Joseph R.
-
supporting information
p. 9139 - 9144
(2020/11/30)
-
- Chemoselective Alkylations with N- and C-Metalated Nitriles
-
Metalated nitriles exhibit complementary chemoselectivities in electrophilic alkylations. N-Lithiated or C-magnesiated nitriles can be prepared from the same nitrile precursor and selectively reacted with a 1:1 mixture of methyl cyanoformate and benzyl br
- Yang, Xun,Nath, Dinesh,Fleming, Fraser F.
-
supporting information
p. 4906 - 4909
(2015/10/12)
-
- BIAROMATIC COMPOUNDS THAT MODULATE PPAR TYPE RECEPTORS, PROCESS FOR PREPARING THEM AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
-
The invention relates to novel biaromatic compounds that correspond to the general formula (I) and also to the method for preparing them, and to their use in pharmaceutical compositions for use in human or veterinary medicine, especially in dermatology, a
- -
-
Page/Page column 44; 1/2
(2010/11/08)
-
- 7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: A study on the importance of modifications at the side chain on the activity and solubility
-
It was demonstrated in the early 1990s that adenosine exerts many physiological functions through the interaction with four different receptors, named A1, A2A, A2B, and A3. In the past few years, our group has been involved in the development of A2A antagonists, which led to the synthesis of SCH 58261 (1), the first potent and selective adenosine A2A antagonist, which has been widely used as a reference compound. In this paper, we present an extended series of pyrazolotriazolopyrimidines synthesized with the aim to investigate the influence of the substitutions on the pyrazole ring. The choice of the substituents was based on their capability to improve water solubility while retaining high affinity and selectivity at the human A2A adenosine receptor subtype. In this series, some structural characteristics that are important for activity, i.e., tricyclic structure, free amino group at 5-position, furan ring, and substituent at 7-position on the pyrazole moiety, have been maintained. We focused our attention on the nature of the phenyl ring substituent to improve water solubility. Following this strategy, we developed new compounds with good affinity and selectivity for A2A adenosine receptors, such as 8d (Ki 0.12 nM; hA1/hA2A ratio = 1025; Rm = 2.8), 8h (Ki 0.22; hA1/hA2A ratio = 9818; Rm = 3.4), 8i (Ki 0.18 nM; hA1/hA2A ratio = 994; Rm = 2.8), 8k (Ki 0.13 nM; hA1/hA2A ratio = 4430; Rm = 3.6), and 14b (Ki 0.19 nM; hA1/hA2A ratio = 2273; Rm = 2.7). All the new synthesized compounds have no significant interaction with either A2B or A3 receptor subtypes. This new series of compounds deeply enlightens some structural requirements to display high affinity and selectivity for the A2A adenosine receptor subtype, although our goal of identifying new compounds with increased water solubility was not completely achieved. On this basis, other strategies will be devised to improve this class of compounds with a profile that appears to be promising for treatment of neurodegenerative disorders, such as Parkinson's disease.
- Baraldi,Cacciari,Romagnoli,Spalluto,Monopoli,Ongini,Varani,Borea
-
p. 115 - 126
(2007/10/03)
-