28057-75-2Relevant academic research and scientific papers
Benzylic C-H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas
Krska, Shane W.,Lin, Shishi,Nkulu, Leah E.,Stahl, Shannon S.,Suh, Sung-Eun
, p. 10380 - 10387 (2021)
C(sp3)-H functionalization methods provide an ideal synthetic platform for medicinal chemistry; however, such methods are often constrained by practical limitations. The present study outlines a C(sp3)-H isocyanation protocol that enables the synthesis of diverse, pharmaceutically relevant benzylic ureas in high-throughput format. The operationally simple C-H isocyanation method shows high site selectivity and good functional group tolerance, and uses commercially available catalyst components and reagents [CuOAc, 2,2′-bis(oxazoline) ligand, (trimethylsilyl)isocyanate, andN-fluorobenzenesulfonimide]. The isocyanate products may be used without isolation or purification in a subsequent coupling step with primary and secondary amines to afford hundreds of diverse ureas. These results provide a template for implementation of C-H functionalization/cross-coupling in drug discovery.
(Partial) agonist/antagonist properties of novel diarylalkyl carbamates on histamine H3 receptors
Sasse,Stark,Ligneau,Elz,Reidemeister,Ganellin,Schwartz,Schunack
, p. 1139 - 1149 (2007/10/03)
In the search for new ligands of the histamine H3 receptor, novel diarylalkyl carbamates (1-19 were synthesized as derivatives of 3-(1H- imidazol-4-yl)propanol and -ethanol. Carbamates were built up via isocyanates either from corresponding amines by reaction with diphosgene or from related carboxylic acid/diphenylphosphoryl azide and the alcoholic component. Sterically hindered amines were prepared in a two-step reaction sequence from corresponding ketones. Some of the title compounds showed (partial) agonist activity at the histamine H3 receptor in vitro and in vivo. Diphenylmethyl carbamate 2 was identified as a new lead structure (ED50 = 5.3 ± 2.6 mg/kg po, α = 1.0). Aromatic substitution in ortho- or para-positions of 2 led to a loss of agonist activity. meta-Substitution was tolerated to some extent. These effects seemed to be caused by steric rather than electronic properties of the substituents. An investigation of exchange of one or both phenyl rings of 2 by heterocyclic rings led to the highly active and selective thienyl derivative 18 (ED50 = 3.4 ± 1.4 mg/kg po, α = 1.0). These new (partial) agonists of the histamine H3 receptor might serve as pharmacological tools for investigating molecular aspects of the H3 receptor or as possible centrally acting therapeutic agents with oral bioavailability. (C) 2000 Elsevier Science Ltd.
Asymmetric Hydrocyanation of Benzaldehydes Catalysed by (5R)-5-(4-Imidazolylmethyl)-2,4-imidazolidinedione
Danda, Hidenori
, p. 3743 - 3745 (2007/10/02)
The catalytic activity of (5R)-5-(4-imidazolylmethyl)-2,4-imidazolidinedione (3) was examined in the asymmetric hydrocyanation of 3-phenoxybenzaldehyde (1a) to (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile ((S)-2a), an important alcohol moiety of optically active pyrethroid insecticides.Among the catalysts, 3-benzyl derivative (3d) exhibited moderate enantioselectivities for 1a and other benzaldehydes.
