187526-92-7Relevant articles and documents
Chiral Cyclopropenimine-catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β-Unsaturated Isoxazoles
Bai, Yu-Jun,Cheng, Mei-Ling,Zheng, Xiao-Hui,Zhang, Sheng-Yong,Wang, Ping-An
supporting information, (2022/04/19)
A highly efficient asymmetric Michael addition of bulky glycine imine to α,β-unsaturated isoxazoles has been achieved by using 5 mol% of chiral cyclopropenimine as a chiral organo-superbase catalyst under mild conditions. Michael adducts were obtained in excellent yields (up to 97%) and stereoselectivities (up to >99 : 1 dr and 98% ee). A significant solvent effect was found in these chiral organosuperbase catalyzed asymmetric Michael reactions. Gram-scale preparation of Michael adducts and their transformations are realized to provide corresponding products without loss of stereoselectivities. The configurations of Michael adduct was determined by single-crystal X-ray diffraction analysis.
Urea based foldamers
Yoo, Sung Hyun,Li, Bo,Dolain, Christel,Pasco, Morgane,Guichard, Gilles
, p. 59 - 92 (2021/06/25)
N,N′-linked oligoureas are a class of enantiopure, sequence-defined peptidomimetic oligomers without amino acids that form well-defined and predictable helical structures akin to the peptide α-helix. Oligourea-based foldamers combine a number of features—such as synthetic accessibility, sequence modularity, and folding fidelity—that bode well for their use in a range of applications from medicinal chemistry to catalysis. Moreover, it was recently recognized that this synthetic helical backbone can be combined with regular peptides to generate helically folded peptide-oligourea hybrids that display additional features in terms of helix mimicry and protein-surface recognition properties. Here we provide detailed protocols for the preparation of requested monomers and for the synthesis and purification of homo-oligoureas and peptide-oligourea hybrids.
Asymmetric Multicomponent Sulfa-Michael/Mannich Cascade Reaction: Synthetic Access to 1,2-Diamino-3-Organosulfur Compounds and 2-Nitro Allylic Amines
Hou, Wenduan,Wei, Qi,Liu, Guisheng,Chen, Jing,Guo, Jing,Peng, Yungui
, p. 4870 - 4873 (2015/10/12)
A novel catalytic asymmetric three-component intermolecular sulfa-Michael/Mannich cascade reaction has been developed using a chiral multifunctional catalyst. This reaction provides facile access to 1-amino-2-nitro-3-organosulfur compounds bearing three c
Enantiodivergent synthesis of Wieland-Miescher ketone analog mediated by a chiral pyridinylmethyl-amine derivative
Honda, Shota,Inomata, Kohei,Endo, Yasuyuki
, p. 950 - 966 (2015/03/04)
A new enantiodivergent route to provide the Wieland-Miescher ketone analog (3b) bearing a 7-membered ring via the intramolecular aldol reaction of the trione (5) mediated by a single chiral pyridinylmethylamine derivative (13e) was established. Although the enantioselectivities of 3b were moderate, the complete inversion of the enantioselectivities was observed based on the amount of additional trifluoroacetic acid (TFA). The basicity of the nitrogen atom on the pyridine ring was very important for this enantiodivergent behavior.
AZAQUINAZOLINE INHIBITORS OF ATYPICAL PROTEIN KINASE C
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Page/Page column 221, (2014/04/17)
The present invention provides a compound of formula (I) or a salt thereof, wherein R7, R8, R9, G, and X are as defined herein. A compound of formula (I) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.
NOVEL SUBSTITUTED ISOQUINOLINE DERIVATIVE
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Paragraph 0686; 0687, (2013/10/22)
The present invention provides a novel isoquinoline-6-sulfonamide derivative that is useful as a medicine. The present invention provides an isoquinoline-6-sulfonamide derivative represented by Formula (1), a salt thereof, or a solvate of the derivative o
Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines
Hunt, Thomas,Atherton-Watson, Hazel C.,Collingwood, Stephen P.,Coote, Kevin J.,Czarnecki, Sarah,Danahay, Henry,Howsham, Catherine,Hunt, Peter,Paisley, Derek,Young, Alice
, p. 2877 - 2879 (2012/05/20)
We report the synthesis and biological evaluation of a series of novel α-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 μg kg-1 at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride.
Discovery and development of an efficient, scalable, and robust route to the novel CENP-E inhibitor GSK923295A
Bellingham, Richard,Buswell, A. Mark,Choudary, Bernie M.,Gordon, Andrew H.,Moore, Steve O.,Peterson, Matthew,Sasse, Mike,Shamji, Amin,Urquhart, Michael W. J.
experimental part, p. 1254 - 1263 (2011/04/24)
The discovery and development of an efficient manufacturing route to the CENP-E inhibitor 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)- 1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl} -4-[(1-methylethyl)oxy]benzamide (GSK923295A) is described. The existing route to GSK923295A was expensive, nonrobust, used nonideal reagents, and consistently struggled to deliver the API needed for clinical studies. The new synthesis commences from the readily available l-phenylalaninol, which is smoothly converted through to GSK923295A using key Friedel-Crafts acylation as well as selective acylation chemistries. Downstream chemistry to GSK923295A is both high yielding and robust, and the resulting process has been demonstrated first on the kilo scale and subsequently in the pilot plant where 55 kg was successfully prepared. The resulting process is simple, uses cheaper raw materials, is greener in that it avoids using aluminum, tin, and bromination chemistries, and obviates the need for chromatographic purification. Also discussed are the route derived impurities, how they were unambiguously prepared to confirm structure and processing amendments to control their formation, and enhancements to the new process to facilitate future processing.
Development of diphenylamine-linked bis(imidazoline) ligands and their application in asymmetric Friedel-Crafts alkylation of indole derivatives with nitroalkenes
Liu, Han,Du, Da-Ming
supporting information; experimental part, p. 1113 - 1118 (2010/07/03)
The new diphenylamine-linked bis(imidazoline) ligands were prepared through Kelly-You's imidazoline formation procedure mediated by Hendrickson 's reagent in good yields. The novel ligands were tested in the asymmetric Friedel-Crafts alkylation of indole derivatives with nitroalkenes. In most cases, good yields (up to 97%) and excellent enantioselectivities (up to 98%) can be achieved. The optimized bis(imidazoline) ligand with trans-diphenyl substitution on the imidazoline ring gave better enantioselectivity than the corresponding bis(oxazoline) ligand.
Discovery of 5-pyrrolopyridinyl-2-thiophenecarboxamides as potent AKT kinase inhibitors
Seefeld, Mark A.,Rouse, Meagan B.,McNulty, Kenneth C.,Sun, Lihui,Wang, Jizhou,Yamashita, Dennis S.,Luengo, Juan I.,Zhang, ShuYun,Minthorn, Elisabeth A.,Concha, Nestor O.,Heerding, Dirk A.
scheme or table, p. 2244 - 2248 (2009/12/07)
A pyrrolopyridinyl thiophene carboxamide 7 was discovered as a tractable starting point for a lead optimization effort in an AKT kinase inhibition program. SAR studies aided by a co-crystal structure of 7 in AKT2 led to the identification of AKT inhibitor
