- Stereoselective construction of deoxy-cruciferane alkaloids by NHC-catalyzed intramolecular annulation of homoenolate with quinazolinone
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Chiral N-heterocyclic carbene (NHC)-catalyzed intramolecular [3 + 2] annulation of enals with an unactivated imine moiety of quinazolinone via formal homoenolate cycloaddition has been demonstrated. It is an excellent approach for stereoselective syntheses of deoxy-cruciferane alkaloids comprising a biologically important pyrroloindoline scaffold. Notably, this is the first report on the NHC-catalyzed asymmetric intramolecular homoenolate annulation with cyclic N-acyl amidine.
- Ahire, Milind M.,Pol, Mahesh D.,Kavale, Dattatry S.,Gonnade, Rajesh G.,Mhaske, Santosh B.
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supporting information
p. 7135 - 7139
(2019/08/07)
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- Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists
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Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCR1 antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model.
- Xie, Yun Feng,Lake, Kirk,Ligsay, Kathleen,Komandla, Mallareddy,Sircar, Ila,Nagarajan, Gobi,Li, Jian,Xu, Kui,Parise, Jason,Schneider, Lisa,Huang, Ding,Liu, Juping,Dines, Kevin,Sakurai, Naoki,Barbosa, Miguel,Jack, Rick
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p. 3367 - 3372
(2008/02/07)
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- Bioisosteric modifications of 2-arylureidobenzoic acids: Selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5
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2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 μM, respectively, compared to compound 2a with IC50 = 4.8 μM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.
- Valgeirsson, Jon,Nielsen, Elsebet ?.,Peters, Dan,Mathiesen, Claus,Kristensen, Anders S.,Madsen, Ulf
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p. 6948 - 6957
(2007/10/03)
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- Nitroquinolone derivatives
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A class of optionally 4-substituted 3-nitro-2-oxo-1,2,3,4-tetrahydroquinoline derivatives are selective non-competitive antagonists of NMDA receptors and/or are antagonists of AMPA receptors, and are therefore of utility in the treatment of conditions, su
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