- Efficient novel eutectic-mixture-mediated synthesis of benzoxazole-linked pyrrolidin-2-one heterocycles
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In this study, new benzoxazole-linked pyrrolidinone heterocyclic compounds were synthesized by an eco-efficient strategy using substituted benzylamines and 2-aminophenol under ultrasonic irradiation in the presence of a newly designed metal-free deep eutectic solvent (DES). This DES was prepared by using a eutectic mixture of urea and a synthesized glycine-derived ionic liquid. X-ray diffraction and infrared spectroscopy were employed to investigate the structure of the ionic liquid and characterize the DES, respectively. This method exhibited key advantages of high productivity, a short reaction time, and simple processing. Moreover, this DES was easily separated from reaction mixtures and can be recycled for multiple reactions.
- Anouar, El Hassane,Geesi, Mohammed H.,Guionneau, Philippe,Kaiba, Abdellah,Ouerghi, Oussama,Riadi, Yassine
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- Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
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A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding Ki and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both Gq-coupled intracellular Ca2+ flux and Gs-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.
- Jurica, Elizabeth A.,Wu, Ximao,Williams, Kristin N.,Hernandez, Andres S.,Nirschl, David S.,Rampulla, Richard A.,Mathur, Arvind,Zhou, Min,Cao, Gary,Xie, Chunshan,Jacob, Biji,Cai, Hong,Wang, Tao,Murphy, Brian J.,Liu, Heng,Xu, Carrie,Kunselman, Lori K.,Hicks, Michael B.,Sun, Qin,Schnur, Dora M.,Sitkoff, Doree F.,Dierks, Elizabeth A.,Apedo, Atsu,Moore, Douglas B.,Foster, Kimberly A.,Cvijic, Mary Ellen,Panemangalore, Reshma,Flynn, Neil A.,Maxwell, Brad D.,Hong, Yang,Tian, Yuan,Wilkes, Jason J.,Zinker, Bradley A.,Whaley, Jean M.,Barrish, Joel C.,Robl, Jeffrey A.,Ewing, William R.,Ellsworth, Bruce A.
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supporting information
p. 1417 - 1431
(2017/03/08)
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- COMPOUNDS COMPRISING A LACTAM OR A LACTAM DERIVATIVE MOIETY, PROCESSES FOR MAKING THEM, AND THEIR USES
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The present invention relates to compounds of formula (I) comprising a lactam or a lactam derivative moiety, processes for preparing them, pharmaceutical compositions comprising said compounds and their uses as pharmaceuticals.
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Page/Page column 78
(2008/06/13)
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- SUBSTITUTED HETEROCYCLES AND METHODS OF USE
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Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 148
(2010/11/08)
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- PYRROLIDONE DERIVATIVES AS MAOB INHIBITORS
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Racemic or enantiomerically pure 4-pyrrolidino derivatives of the formula (I), processes for their preparation, pharmaceutical compositions comprising said derivatives, and their use in the prevention and treatment of a disease which is mediated by a mono
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- Synthesis of 4-methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosynthesis
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The synthesis of a series of 4-methyloxybenzoic acids and related compounds, and their evaluation for inhibitory capacity toward fatty-acid and sterol biosyntheses using rats' liver slices in vitro and rabbits
- Watanabe, S.,Ogawa, K.,Ohno, T.,Yano, S.,Yamada, H.,Shirasaka, T.
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p. 675 - 686
(2007/10/02)
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- Phenylcarboxylic acid derivatives having hetero ring
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Phenylcarboxylic acid derivatives having a hetero ring in the substituent of the formula: STR1 wherein R1 is halogen, alkyl, cycloalkyl, hydroxy, alkoxy, phenoxy which has a substituent selected from halogen and alkyl, carboxyl, alkylsulfonyloxy, phenylsulfonyloxy optionally substituted by halogen, alkylsulfonyloxyalkoxy, amino, alkanoylamino, benzoylamino, alkenyloxy, phenylalkoxyalkoxy, hydroxyalkoxy, phenylalkoxy having optionally 1 to 3 substituents selected from halogen, alkyl and alkoxy, halogenoalkyl, cycloalkyloxy optionally substituted by hydroxy, alkoxy substituted by cycloalkyl having optionally hydroxy substituent, imidazolylalkyl or imidazolylalkoxy; k is 0 or 1 to 3; or (R1)k is alkylenedioxy; A is alkylene or alkylenoxy; l is 0 or 1; B is methylene or carbonyl; m is 0 or 1; D is alkylene; E is alkylene or alkenylene; n is 0 or 1; and R2 is hydrogen or alkyl, or a salt thereof, which have fatty acid synthesis-inhibitory activity, cholesterol synthesis-inhibitory activity and are useful as antilipidemic agent, prophylactic and treating agent of arteriosclerosis, prophylactic and treating agent of obesity, antidiabetics.
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