- Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties
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Herein we report investigations into the p38α MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation.
- Mader, Mary,de Dios, Alfonso,Shih, Chuan,Bonjouklian, Rosanne,Li, Tiechao,White, Wesley,de Uralde, Beatriz Lopez,Sanchez-Martinez, Concepcion,del Prado, Miriam,Jaramillo, Carlos,de Diego, Eugenio,Martin Cabrejas, Luisa M.,Dominguez, Carmen,Montero, Carlos,Shepherd, Timothy,Dally, Robert,Toth, John E.,Chatterjee, Arindam,Pleite, Sehila,Blanco-Urgoiti, Jaime,Perez, Leticia,Barberis, Mario,Lorite, Maria Jose,Jambrina, Enrique,Nevill Jr., C. Richard,Lee, Paul A.,Schultz, Richard C.,Wolos, Jeffrey A.,Li, Li C.,Campbell, Robert M.,Anderson, Bryan D.
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Read Online
- Effective synthesis of benzimidazoles-imidazo[1,2-a]pyrazine conjugates: A comparative study of mono-and bis-benzimidazoles for antitumor activity
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A novel series of 6-substituted-8-(1-cyclohexyl-1H-benzo[d]imidazole-6-yl)imidazo[1,2-a]pyrazine and 6-substituted-8-(1-benzyl-1H-benzo[d]imidazole-6-yl)imidazo[1,2-a]pyrazine is first time synthesized and screen in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Derivatives 10 and 36 show antitumor activity for all tested cell lines, display comparable full panel mean-graph midpoint growth inhibition (MG_MID GI50) values of 2.10 and 2.23 μM, respectively. Furthermore, these derivatives show strong binding interactions with DNA and bovine serum albumin (BSA), studied through absorption, emission, and circular dichroism techniques. These spectroscopic studies reveal that imidazo[1,2-a]pyrazine-benzimidazoles 10 and 36, intercalate with ct-DNA as a leading interaction for fundamental biologically significant effects, with monobenzimidazole show better activity than bisbenzimidazole. These experiments have confirmed that the imidazo[1,2-a]pyrazine and benzimidazole moieties are efficient pharmacophores to trigger binding to DNA. These compounds have also interacted with bovine serum albumin protein that demonstrating high values of binding constant.
- Singh, Iqubal,Luxami, Vijay,Paul, Kamaldeep
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p. 546 - 561
(2019/08/01)
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- Synthesis and: In vitro evaluation of naphthalimide-benzimidazole conjugates as potential antitumor agents
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A series of novel naphthalimide-benzimidazoles was designed and synthesized for the first time and studied for their effect on antiproliferative activity. Some of these compounds possessed good antitumor activity towards the tested cancer cell lines. Noticeably, (diethylamino)ethyl 15 and (dimethylamino)ethyl 23 derivatives displayed superior antiproliferative activity towards human cancer cell lines with MG-MID GI50 values of 1.43 and 1.83 μM, respectively. Preliminary investigation revealed that compounds 15 and 23 might bind with ct-DNA through the intercalation mode which is responsible for potent bioactivity. Moreover, transportation behaviour indicated that these molecules could efficiently bind to and be carried by bovine albumin, and the hydrogen bonding and hydrophobic interactions played important roles in interaction with serum albumin.
- Singh, Iqubal,Luxami, Vijay,Paul, Kamaldeep
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p. 5349 - 5366
(2019/06/07)
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- Synthesis and photophysical properties of ruthenium(ii) polyimine complexes decorated with flavin
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A bipyridine ruthenium(ii) complex (Ru-1) with a flavin moiety connected to one of the bipyridine ligands via an acetylene bond was designed and synthesized, and its photophysical properties were investigated. Compared with the tris(bipyridine) Ru(ii) com
- Guo, Huimin,Zhu, Lijuan,Dang, Can,Zhao, Jianzhang,Dick, Bernhard
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p. 17504 - 17516
(2018/07/06)
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- ORGANIC COMPOUND, AND ORGANIC LIGHT EMITTING DIODE AND ORGANIC LIGHT EMITTING DISPLAY DEVICE INCLUDING THE SAME
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The present invention provides an organic compound for an organic light emitting diode. An example of the organic compound is represented by:
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Paragraph 0135; 0136
(2018/05/24)
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- Importance of 5/6-aryl substitution on the pharmacological profile of 4?-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1?-biphenyl]-2-carboxylic acid derived PPARγ agonists
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In this structure-activity relationship study, the influence of aryl substituents at position 5 or 6 on the pharmacological profile of the partial PPARγ agonist 4‘-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1‘-biphenyl]-2-carboxylic acid was investigated. This lead was previously identified as the essential part of telmisartan to induce PPARγ activation. Para-OCH3-phenyl substitution strongly increased potency and efficacy independent of the position. Both compounds represent full agonists because of strong hydrophobic contacts with the amino acid Phe363 in the ligand binding domain. Partial agonists with higher potency than telmisartan or the lead were obtained with OH or Cl substituents at the phenyl ring. Molecular modeling suggested additional hydrogen or halogen bonds with Phe360 located at helix 7. It is assumed that these interactions fix helix 7, thereby promoting a partial agonist conformation of the receptor. The theoretical considerations correlate very well with the results from the luciferase transactivation assay using hPPARγ-LBD as well as those from a time-resolved fluorescent resonance energy transfer (TR-FRET) assay in which the coactivator (TRAP220, PGC-1α) recruitment and corepressor (NCoR1) release pattern was investigated.
- Obermoser, Victoria,Mauersberger, Robert,Schuster, Daniela,Czifersky, Monika,Lipova, Marina,Siegl, Monika,Kintscher, Ulrich,Gust, Ronald
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supporting information
p. 590 - 603
(2016/12/09)
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- Substituted benzimidazole derivatives
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The invention belongs to the field of pharmaceutical chemistry, particularly relates to substituted benzimidazole derivatives as well as a preparation method and pharmaceutical composition thereof and further relates to an application of the substituted b
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Paragraph 0176; 0178; 0179
(2018/01/09)
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- NOVEL ORGANIC ELECTROLUMINESCENT COMPOUNDS AND ORGANIC ELECTROLUMINESCENT DEVICE USING THE SAME
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The present invention relates to a novel organic electroluminescent compound and an organic electroluminescent device containing the same. Using the organic electroluminescent compounds of the present invention, it is possible to manufacture an OLED devic
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Paragraph 146-147
(2013/06/27)
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- NOVEL ORGANIC ELECTROLUMINESCENCE COMPOUNDS AND ORGANIC ELECTROLUMINESCENCE DEVICE USING THE SAME
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The present invention relates to novel organic electroluminescence compounds and an organic electroluminescence device containing the same. The compounds according to the present invention have high luminous efficiency and long operation lifetime. Therefore, they can produce an organic electroluminescence device having enhanced power consumption efficiency.
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Paragraph 154-156
(2013/03/26)
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- NOVEL COMPOUND FOR ORGANIC ELECTRONIC MATERIAL AND ORGANIC ELECTROLUMINESCENT DEVICE USING THE SAME
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Provided are a novel compound for an organic electronic material and an organic electroluminescent device using the same. The compound for an organic electronic material according to the present invention has high electron transport efficiency, thereby preventing crystallization at the time manufacturing of a device, and allows a layer to be easily formed, thereby improving current characteristics of the device, and thus an OLED device having a lowered driving voltage and improved power efficiency as well as superior luminous efficiency and lifespan characteristics as compared with the existing material can be manufactured.
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Page/Page column 38
(2012/06/01)
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- Ethylammonium nitrate (EAN)/Tf2O and EAN/TFAA: Ionic liquid based systems for aromatic nitration
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Acting as in situ sources of triflyl nitrate (TfONO2) and trifluoroacetyl nitrate (CF3COONO2), the EAN/Tf 2O and EAN/TFAA systems, generated via metathesis in the readily available ethylammonium nitrate (EAN) ionic liquid as solvent, are powerful electrophilic nitrating reagents for a wide variety of aromatic and heteroaromatic compounds. Comparative nitration experiments indicate that EAN/Tf2O is superior to EAN/TFAA for nitration of strongly deactivated systems. Both systems exhibit low substrate selectivity (K T/KB = 5-10) in (Figure presented) between values reported for covalent nitrates and preformed nitronium salts.
- Aridoss, Gopalakrishnan,Laali, Kenneth K.
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experimental part
p. 8088 - 8094
(2011/11/13)
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- PROTEIN KINASE INHIBITORS
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The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof which is useful in the treatment of cell proliferative diseases.
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Page/Page column 9
(2010/07/04)
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- Sparing the Ortho-position in Nucleophilic Aromatic Substitution-Specific Displacement of the 4-SePh Group in 2,4-Bis(phenylseleno)nitrobenzene
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Upon treatment of o- and p- (phenylseleno)nitrobenzenes with sodium methoxide quantitative exchange reactions took place, affording the corresponding methoxynitrobenzenes. Upon reaction between 2,4-bis(phenylseleno) nitrobenzene 2 and sodium methoxide, an unusual regiopure formation of 4-methoxy-2-(phenylseleno)nitrobenzene 3 was observed. This product remained unreactive toward an excess of sodium methoxide, thus preventing the formation of 2,4-dimethoxynitrobenzene 6. The nature of the reactants and of the intermediate Meisenheimer complexes was examined by synthetic investigations, x-ray crystallography, and DFT calculations. We found that the observed selectivity can be understood in terms of traditional resonance considerations.
- Nicolai, Stuhr-Hansen,Goetze, Thorstein Finn,Henriksen, Lars,Solling, Theis Ivan,Langkilde, Annette,Sorensen, Henning Osholm
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experimental part
p. 101 - 108
(2009/09/25)
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- BICYCLIC TRIAZOLES AS PROTEIN KINASE MODULATORS
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The present disclosure provides bicyclic triazole protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.
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Page/Page column 82
(2008/12/05)
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- NOVEL JNK INHIBITORS
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Disclosed are compounds of the formula (I) wherein X is N or CH, and Y is N or CR5. Also disclosed are methods of treating JNK and ERK mediated diseases using the compounds of formula 1.0.
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Page/Page column 109
(2008/12/07)
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- VIRAL POLYMERASE INHIBITORS
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An enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein either A or B is nitrogen and the other B or A is C, and the radicals R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein, or a salt or ester thereof as viral polymerase inhibitors. The compound is used as an inhibitor of RNA dependent RNA polymerases, particularly those viral polymerases within the Flaviviridae family, more particularly to HCV polymerase.
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Page/Page column 93
(2008/06/13)
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- 4- (HETEROCYCLYL- FUSED PHENYL)- 3- (PHENYL OR PYRID -2- YL) PYRAZOLES AS INHIBITORS OF THE ALK-5- RECEPTOR
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The invention relates to novel pyrazole derivatives which are inhibitors of the transforming growth factor, ("TGF")-β signalling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-β type I or activin-like kinase ("ALK")-5 receptor, m
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- COMPOUNDS
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The invention relates to novel aminothiazole derivatives which are inhibitors of the transforming growth factor, ("TGF")-? signaling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-? type I or activin-like kinase ("ALK")-5 recepto
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Page/Page column 17
(2010/02/10)
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