- Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors
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Spirocyclic secondary amine-derived trisubstituted ureas were identified as highly potent, bioavailable and selective soluble epoxide hydrolase (sEH) inhibitors. Despite good oral exposure and excellent ex vivo target engagement in blood, one such compoun
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Read Online
- EIF4A-INHIBITING COMPOUNDS AND METHODS RELATED THERETO
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The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula I, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof. For Formula I compounds X, Y, R1, R2, R3a, R3b, R4a, R4b and R5 are as defined in the specification. The inventive Formula I compounds are inhibitors of eIF4A and find utility in any number of therapeutic applications, including but not limited to treatment of inflammation and various cancers.
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Paragraph 0622; 0623
(2017/08/01)
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- Lithiation of a silyl ether: Formation of an ortho-fries hydroxyketone
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A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE=complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, are reported.
- Lo, Hong-Jay,Lin, Chin-Yin,Tseng, Mei-Chun,Chein, Rong-Jie
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p. 9026 - 9029
(2014/09/17)
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- TRICYCLIC SPIROCYCLE DERIVATIVES AND METHODS OF USE
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The present invention relates to novel Tricyclic Spirocycle Derivatives, pharmaceutical compositions comprising the Tricyclic Spirocycle Derivatives and the use of these compounds for treating or preventing allergy, an allergy-induced airway response, congestion, a cardiovascular disease, an inflammatory disease, a gastrointestinal disorder, a neurological disorder, a metabolic disorder, obesity or an obesity-related disorder, diabetes, a diabetic complication, impaired glucose tolerance or aired fasting glucose.
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Page/Page column 49
(2011/07/29)
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- HETEROCYCLIC COMPOUND
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The present invention provides a compound having an ACC inhibitory action, which is useful for the prophylaxis or treatment of obesity, diabetes, hypertension, hyperlipidemia, cardiac failure, diabetic complications, metabolic syndrome, sarcopenia, cancer and the like, and has superior efficacy. The present invention provides a compound represented by the formula (I): wherein each symbol is as in the specification, or a salt thereof.
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Page/Page column 63
(2009/12/07)
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- GEM-DISUBSTITUTED AND SPIROCYCLIC AMINO PYRIDINES/PYRIMIDINES AS CELL CYCLE INHIBITORS
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Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of CDK4-mediated disorders, such as cancer. The subject compounds are gem-disubstituted or spirocyclic pyridine, pyrimidine and triazine derivatives.
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Page/Page column 62-63
(2009/11/29)
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- Method of Preparation of Benzofuran-2-Carboxylic Acid -Amide
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This invention relates to a method of preparation of benzofuran-2-carboxylic acid {(S)-3-methyl-1-[(4S,7R)-7-methyl-3-oxo-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-butyl}-amide.
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Page/Page column 14-15
(2008/12/04)
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- Furopyridines.III.A New Synthesis of Furopyridine
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A convenient synthesis of furopyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxypicolinate (1) is described.The hydroxy ester 1 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 2a or 2b.Cyclization of compound 2a afforded ethyl 3-hydroxyfuropyridine-2-carboxylate (3) which in turn was hydrolyzed and decarboxylated to give furopyridin-3-(2H)-one (4a).Cyclization of 2b gave the 2-methyl derivative 4b.Reduction of 4a and 4b with sodium borohydride yielded the corresponding hydroxy derivative 5a and 5b respectively, which were dehydrated with phosphoric acid to give furopyridine (6a) and its 2-methyl derivative (6b). 2-Acetylpyridin-3-ol (8) was converted to the ethoxycarbonylmethyl ether (9) by O-alkylation with ethyl bromoacetate, which was cyclized to give 3-methylfuropyridine-2-carboxylic acid (10).Decarboxylation of 10 afforded 3-methylfuropyridine (11).
- Shiotani, Shunsaku,Morita, Hiroyuki
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p. 665 - 668
(2007/10/02)
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