- Electrochemically Enabled Intramolecular Aminooxygenation of Alkynes via Amidyl Radical Cyclization
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An electrochemical synthesis of oxazol-2-ones and imidazol-2-ones has been developed via 5-exo-dig cyclization of propargylic carbamates- and ureas-derived amidyl radicals. The electrosynthesis relies on the dual function of 2,2,6,6-tetramethylpiperidin- 1-yl)oxyl (TEMPO) as a redox mediator for amidyl radical formation and an oxygen atom donor. The reactions are conducted under mild conditions using a simple setup and provide convenient access to functionalized oxazol-2-ones and imidazol-2-ones from readily available materials.
- Hou, Zhong-Wei,Xu, Hai-Chao
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supporting information
p. 394 - 398
(2020/03/04)
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- 1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: Structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain
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1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to investigate their structure-activity relationships as inhibitors of the human and murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhibitors. For example, 1-(1-(cyclopropanecarbonyl) piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (52) showed a 7-fold increase in potency, a 65-fold increase in Cmax, and a 3300-fold increase in AUC over its adamantane analogue 1-(1-adamantyl)-3-(1-propionylpiperidin-4-yl) urea (2). This novel sEH inhibitor showed a 1000-fold increase in potency when compared to morphine by reducing hyperalgesia as measured by mechanical withdrawal threshold using the in vivo carrageenan induced inflammatory pain model.
- Rose, Tristan E.,Morisseau, Christophe,Liu, Jun-Yan,Inceoglu, Bora,Jones, Paul D.,Sanborn, James R.,Hammock, Bruce D.
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supporting information; experimental part
p. 7067 - 7075
(2010/12/25)
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- Oxime Carbamate-Discovery of a series of novel FAAH inhibitors
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A series of novel oxime carbamates have been identified as potent inhibitors of the key regulatory enzyme of the endocannabinoid signaling system, fatty acid amide hydrolase (FAAH). In this Letter, the rationale behind the discovery and the biological evaluations of this novel class of FAAH inhibitors are presented. Both in vitro and in vivo results of selected targets are discussed, along with inhibition kinetics and molecular modeling studies.1.
- Sit,Conway, Charles M.,Xie, Kai,Bertekap, Robert,Bourin, Clotilde,Burris, Kevin D.
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supporting information; experimental part
p. 1272 - 1277
(2010/06/17)
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- Piperidine-containing histamine H3 receptor antagonists of the carbamate series: The influence of the additional ether functionality
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Recently novel leads for histamine H3 receptor antagonists of the non-imidazole type have been described. As a continuation of this research eleven new carbamate derivatives possessing an additional ether functionality were prepared. The compounds were evaluated in vitro for their antagonist activity on isolated organs of guinea-pig (GP) H3 as well as H2, H1, and M3 receptors, respectively. All compounds investigated possessed moderate antagonist affinities at guinea-pig histamine H3 receptors (pA2 6.11-6.76). An ether functionality introduced in different places of the lipophilic part of carbamates differently influenced activity and selectivity toward H3, M3, and other histamine receptors tested.
- Lazewska,Kiec-Kononowicz, Katarzyna,Pertz,Elz,Stark,Schunack
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p. 791 - 795
(2007/10/03)
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