32025-38-0Relevant academic research and scientific papers
Ruthenium-Catalyzed Enantioselective Hydrogenation/Lactonization of 2-Acylarylcarboxylates: Direct Access to Chiral 3-Substituted Phthalides
Lu, Bin,Zhao, Mengmeng,Ding, Guangni,Xie, Xiaomin,Jiang, Lili,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
, p. 3989 - 3996 (2017/09/13)
Highly enantioselective tandem hydrogenation/lactonization of various 2-acylarylcarboxylates including 2-aroylarylcarboxylates were realized by using [RuCl(benzene)(S)-SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3-substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram-scale reaction was performed to further demonstrate the practicality of this approach.
Palladium-Catalyzed Environmentally Benign Acylation
Suchand, Basuli,Satyanarayana, Gedu
, p. 6409 - 6423 (2016/08/16)
Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp2 C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.
Discovery of Potent, orally bioavailable phthalazinone bradykinin B1 receptor antagonists
Biswas, Kaustav,Peterkin, Tanya A. N.,Bryan, Marian C.,Arik, Leyla,Lehto, Sonya G.,Sun, Hong,Hsieh, Feng-Yin,Xu, Cen,Fremeau, Robert T.,Allen, Jennifer R.
experimental part, p. 7232 - 7246 (2012/01/03)
The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.
