- Discovery of (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide as potent and isoform selective ROCK2 inhibitors
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ROCK1 and ROCK2 are highly homologous isoforms. Accumulated studies indicate that they have distinct different functions, and the development of isoform selective ROCK inhibitors will pave new roads for the treatment of various diseases. In this work, a series of amide-chroman derivatives were synthesized and biologically evaluated in order to develop potent and isoform selective ROCK2 inhibitors. Remarkably, (S)-6-methoxy-chroman-3-carboxylic acid (4-pyridin-4-yl-phenyl)-amide ((S)-7c) possessed ROCK2 inhibitory activity with an IC50 value of 3 nM and 22.7-fold isoform selectivity (vs. ROCK1). Molecular docking indicated that hydrophobic interactions were the key element for the high potency and isoform selectivity of (S)-7c. The binding free energies predicted by MM/GBSA were in good agreement with the experimental bioactivities, and the analysis of individual energy terms suggested that residue Lys105 in ROCK1 or Lys121 in ROCK2 was the key residue for the isoform selectivity of (S)-7c.
- Pan, Jinpeng,Yin, Yan,Zhao, Lianhua,Feng, Yangbo
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p. 1382 - 1390
(2019/02/26)
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- DUAL AGONISTS OF FXR AND PPARδ AND THEIR USES
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The present invention relates to small molecule compounds and their use as agonists of farnesoid X receptor (FXR) and/or peroxisome proliferator activated receptor delta (PPARδ). The present invention also relates to the use of said compounds in the treatment of metabolic diseases and respective methods of treatment.
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Page/Page column 38; 46
(2019/04/16)
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- Strong base- or acid-mediated chemoselectivity shifts in the synthesis of 2H-chromene or coumarin derivatives from common Baylis-Hillman adducts
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Abstract Reaction of tert-butyl 3-(2-hydroxyphenyl)-2-methylenepropanoate esters with aqueous KOH provides convenient and chemoselective one-pot access to 2H-chromene-3-carboxylic acids, the overall transformation involving tandem conjugate addition, hydrolysis and elimination steps. The methodology complements the chemoselective, acid-catalysed route to 3-substituted coumarins from the same substrates by switching the regioselectivity of cyclisation.
- Faridoon,Olomola, Temitope O.,Tukulula, Matshawandile,Klein, Rosalyn,Kaye, Perry T.
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p. 4868 - 4873
(2015/08/03)
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- 10-Camphorsulfonic acid ((±)-CSA) catalyzed facile one-pot synthesis of a new class of 2,5-disubstituted 1,3,4-oxadiazoles
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A convenient and efficient one-pot synthesis of 2,5-disubstituted-1,3,4-oxadizoles is described. Various carboxylic acid hydrazides reacted efficiently with different carboxylic acid chlorides and 10-camphorsulfonic acid. This methodology was successfully
- Mule, Siva Nagi Reddy,Battula, Sailaja Kumari,Velupula, Ganapathi,Guda, Dinneswara Reddy,Bollikolla, Hari Babu
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p. 58397 - 58403
(2015/02/19)
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- 3-nitro-2H-chromenes as a new class of inhibitors against thioredoxin reductase and proliferation of cancer cells
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A series of 3-nitrochromenes were designed and synthesized. These compounds showed good inhibitory activity against thioredoxin reductase (TrxR) and the proliferation of A549 cancer cells. The structure-activity relationship analysis indicates that the 3-nitrochromene scaffold is the crucial pharmacophore for achieving good inhibitory activity. The bromo-substitutions at the 6- and 8-position of 3-nitrochromene significantly increase the inhibitory activity. A series of 3-nitrochromenes were designed and synthesized. They showed good inhibitory activity against thioredoxin reductase and the proliferation of A549 cancer cells. Structure-activity relationship analysis revealed that the 3-nitrochromene scaffold is the crucial pharmacophore for achieving good inhibitory activity. Bromo-substitutions at the 6- and 8-position of 3-nitrochromene significantly increase the inhibitory activity. Copyright
- Xiao, Guo-Qiang,Liang, Bao-Xia,Chen, Shu-Han,Ou, Tian-Miao,Bu, Xian-Zhang,Yan, Ming
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p. 767 - 770
(2013/01/15)
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- NOVEL CHROMENE AND THIOCHROMENE CARBOXAMIDE DERIVATIVES, METHODS FOR PREPARING SAME AND THERAPEUTIC APPLICATIONS OF SAME
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The present invention relates to novel chromene or thiochromene carboxamide derivatives, the preparation of same, pharmaceutical compositions of same and the use of same as dopamine D3 ligands as a medicament for central nervous system disorders.
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Page/Page column 38-39
(2008/06/13)
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- QUATERNARY SALT CCR2 ANTAGONISTS
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Quaternary salt compounds of Formula (I) or pharmaceutically acceptable forms thereof, which are CCR2 antagonists and are useful in preventing, treating or ameliorating CCR2 mediated inflammatory syndromes, disorders or diseases in a subject in need thereof.
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Page/Page column 75-77
(2008/06/13)
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- Quaternary salt CCR2 antagonists
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Quaternary salt compounds of Formula (I) or pharmaceutically acceptable forms thereof, which are CCR2 antagonists and are useful in preventing, treating or ameliorating CCR2 mediated inflammatory syndromes, disorders or diseases in a subject in need thereof.
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Page/Page column 81
(2008/06/13)
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- 6-Chloro-2,3-Dihydro-4H-1-Benzopyran Carboxylic Acids: Synthesis, Optical Resolution and Absolute Configuration
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6-Chloro-2,3-dihydro-4H-1-benzopyran-2-carboxylic acid, a rigid analogue of clofibric acid, the active metabolite of the antilipidemic drug clofibrate, has been prepared together with two isomers, 6-chloro-2,3-dihydro-4H-1-benzopyran-3- and 4-carboxylic a
- Loiodice, Fulvio,Longo, Antonio,Bianco, Pasquale,Tortorella, Vincenzo
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p. 1001 - 1012
(2007/10/03)
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- Chromene and Chroman 3-Carboxamides and Some Related Compounds as a New Class of Centrally Acting Agents
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A number of chromene-3-carboxamides (7), 3-Aminochromans (11) and 3-aminomethylchromans (9) have been synthesized.Chromene-3-carboxamides have been found to exhibit strong central muscle relaxant activity compared to mephesin.
- Gupta, R. C.,Pratap, Ram,Prasad, C. R.,Anand, Nitya
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p. 344 - 347
(2007/10/02)
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