- A practical synthesis of 2,2-difluoro-3-amino-propanoic acid (α,α-difluoro-β-alanine)
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Reformatsky reaction of ethyl bromodifluoroacetate with N,N-(dibenzyl)-1H-benzotriazolyl-1-methylamine gave fully protected α,α-difluoro-β-alanine. Hydrogenolysis and hydrolysis furnished α,α-difluoro-β-alanine. Further transformation into N-phthalimido-α,α-difluoro-β-alanine was described.
- Cheguillaume, Arnaud,Lacroix, Simon,Marchand-Brynaert, Jacqueline
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- NOVEL COMPOUNDS FOR THE TREATMENT OF PARASITIC INFECTIONS
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The present invention relates to novel compounds or pharmaceutically acceptable salts thereof, corresponding compositions, and methods and/or uses in therapy, for example in the treatment of parasitic infections such as malaria, in particular infection by
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Page/Page column 37; 38
(2019/08/14)
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- HETEROCYCLIC COMPOUND
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The present invention provides a heterocyclic compound having a CDK8 and/or CDK19 inhibitory effect. The present invention provides a compound represented by formula (I) (in the formula, the symbols are as defined in the description) or a salt thereof.
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Paragraph 0564; 0973; 0974
(2017/04/11)
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- Heterocyclic compound
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本發明提供一種具有CDK8/19抑制活性之雜環化合物。本發明提供一種如下式代表之化合物(其中各代號均如本文之定義)或其鹽。 The present invention provides a heterocyclic compound possessing CDK8/19 inhibitory activity. The present invention provides a compound represented by the formula wherein each symbol is as defined herein, or a salt thereof.
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Paragraph 0334; 0335
(2017/09/28)
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- Synthesis of Gly-ψ[(Z)CFCH]-Phe, a Fluoroalkene Dipeptide Isostere, and Its Incorporation into a Leu-enkephalin Peptidomimetic
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A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-ψ[(Z)CFCH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin following the Fmoc strategy. The peptidomimetic was characterized using competition binding with [125I]-deltorphin I on membrane extracts of HEK293 cells expressing the mouse delta opioid receptor (DOPr) and based on its abilities to inhibit the electrically induced contractions of the mouse vas deferens and to activate the ERK1/2 signaling pathway in DRGF11/DOPr-GFP cells. Together with our previous observations, our findings strongly suggest that the third amide bond of Leu-enkephalin primarily acts as a hydrogen bond acceptor in DOPr. Consequently, this amide bond can be successfully replaced by an ester, a thioamide, or a fluoroalkene without greatly impacting the binding or biological activity of the corresponding analogs. The lipophilicity (LogD7.4) of the active analog was also measured. It appears that fluoroalkenes are almost as efficient at increasing the lipophilicity as normal alkenes.
- Nadon, Jean-Fran?ois,Rochon, Kristina,Grastilleur, Sébastien,Langlois, Guillaume,Dao, Thi Thanh Hà,Blais, Véronique,Guérin, Brigitte,Gendron, Louis,Dory, Yves L.
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- HETEROARYL SUBSTITUTED AMINOPYRIDINE COMPOUNDS
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Disclosed are compounds of Formula (I) Formula(I) or salts thereof, wherein HET is a heteroaryl selected from oxazolyl, pyrazolyl, imidazo[l,2-b]pyridazin-3-yl, and pyrazolo[l,5-a]pyrimidin-3-yl, wherein said heteroaryl is attached to the pyridinyl group in the compound of Formula (I) by a carbon ring atom in the heteroaryl and wherein said heteroaryl is substituted with zero to 2 Rb; and R1, R3, and Rb are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.
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Page/Page column 170; 171
(2017/01/09)
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- HETEROARYL SUBSTITUTED NICOTINAMIDE COMPOUNDS
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Disclosed are compounds of Formula (I) or salts thereof, wherein: HET is a heteroaryl selected from pyrazolyl, indolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-d]pyrimidinyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-d]pyrimidinyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, imidazo[4,5-b]pyridinyl, and purinyl, wherein said heteroaryl is substituted with Ra and Rb; and R1 and R2 are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.
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Paragraph 0521
(2015/07/15)
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- HETEROARYL SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS KINASE MODULATORS
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Compounds having the following formula (I) or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein R2 is a monocyclic heteroaryl group, and R1, R3, R4, R5 and R6 are as defined herein, are useful as kinase modulators, including IRAK-4 inhibition.
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Paragraph 00331
(2019/03/15)
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- DIHYDROIMIDAZO [ 1, 5-F] PTERIDINES AS POLO-LIKE KINASE INHIBITORS
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The present invention provides PLK inhibitors of the formula (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using the compounds.
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Page/Page column 17-20
(2010/04/06)
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- POLO-LIKE KINASE INHIBITORS
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Compounds of the following formula are provided for use with kinases: (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates use
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Page/Page column 235; 236
(2009/05/29)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.
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Page/Page column 460-461
(2010/11/27)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula (Ia) and (Ib) wherein A, B, C and R1 are described herein.
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Page/Page column 314-315
(2010/11/27)
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