954112-61-9Relevant articles and documents
Further modifications of 1H-pyrrolo[2,3-b]pyridine derivatives as inhibitors of human neutrophil elastase
Giovannoni, Maria P.,Cantini, Niccolò,Crocetti, Letizia,Guerrini, Gabriella,Iacovone, Antonella,Schepetkin, Igor A.,Vergelli, Claudia,Khlebnikov, Andrei I.,Quinn, Mark T.
, p. 617 - 628 (2019/04/30)
Human neutrophil elastase (HNE) is a potent protease that plays an important physiological role in many processes and is considered to be a multifunctional enzyme. HNE is also involved in a variety of pathologies affecting the respiratory system. Thus, compounds able to inhibit HNE proteolytic activity could represent effective therapeutics. We present here a new series of pyrrolo[2,3-b]pyridine derivatives of our previously reported potent HNE inhibitors. Our results show that position 2 of the pyrrolo[2,3-b]pyridine scaffold must be unsubstituted, and modifications of this position resulted in loss of HNE inhibitory activity. Conversely, the introduction of certain substituents at position 5 was tolerated, with retention of HNE inhibitory activity (IC50 = 15–51 nM) after most substitutions, indicating that bulky and/or lipophilic substituents at position 5 probably interact with the large pocket of the enzyme site and allow Michaelis complex formation. The possibility of Michaelis complex formation between Ser195 and the ligand carbonyl group was assessed by molecular docking, and it was found that highly active HNE inhibitors are characterized by geometries favorable for Michaelis complex formation and by relatively short lengths of the proton transfer channel via the catalytic triad.
FURANONE DERIVATES AND METHODS OF USE THEREOF
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Paragraph 0218, (2018/05/24)
Herein disclosed are compounds, compositions, kits, and methods of treating cancers using 7-azaindolyl furanone/thiophene derivatives. These derivatives inhibit serine-threonine kinase Cdc7, a recognized anticancer target affecting DNA replication. Further, the compounds disclosed herein possess potent inhibitory activity in the presence of adenosine triphosphate (ATP), demonstrate significant kinase selectivity, and offer advantages over known Cdc7 inhibitors with prolonged half-life and inhibitory effects.
Discovery of novel furanone derivatives as potent Cdc7 kinase inhibitors
Irie, Takayuki,Asami, Tokiko,Sawa, Ayako,Uno, Yuko,Hanada, Mitsuharu,Taniyama, Chika,Funakoshi, Yoko,Masai, Hisao,Sawa, Masaaki
, p. 406 - 418 (2017/03/11)
Cdc7 is a serine-threonine kinase and plays a conserved and important role in DNA replication, and it has been recognized as a potential anticancer target. Herein, we report the design, synthesis and structure-activity relationship of novel furanone derivatives as Cdc7 kinase inhibitors. Compound 13 was identified as a strong inhibitor of Cdc7 with an IC50 value of 0.6?nM in the presence of 1?mM ATP and showed excellent kinase selectivity. In addition, it exhibited slow off-rate characteristics, which may offer advantages over known Cdc7 inhibitors in its potential to yield prolonged inhibitory effects in?vivo. Compound 13 potently inhibited Cdc7 activity in cancer cells, and effectively induced cell death.
THERAPEUTIC INHIBITORY COMPOUNDS
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Page/Page column 315, (2015/07/16)
The invention provides compounds of Formula I and Formula II: A-B-C-D-E-F-G-J (I) C-D-E-F-G-J (II) wherein A, B, C, D, E, F, G, and J have any of the values defined in the specification, and salts thereof. The compounds are useful for inhibiting plasma kallikrein, and for treating a disease or condition in an animal where inhibition of plasma kallikrein is indicated.
Compounds and methods for kinase modulation, and indications therefor
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Page/Page column 176; 177, (2015/09/22)
Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereo
NOVEL FURANONE DERIVATIVE
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, (2014/02/16)
To provide a novel furanone derivative, and a medicine including the same. The furanone derivative is represented by the formula (I): wherein A represents —COOR1 or a hydrogen atom; R1 represents a hydrogen atom, an optionally substituted hydrocarbon grou
NEW IMIDAZOLONE DERIVATIVES, PREPARATION THEREOF AS DRUGS, PHARMACEUTICAL COMPOSITIONS, AND USE THEREOF AS PROTEIN KINASE INHIBITORS, IN PARTICULAR CDC7
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Page/Page column 36, (2009/10/17)
The present invention relates to imidazolone derivatives of formula (I) to methods of preparing such derivatives, intermediates thereto, pharmaceutical compositions comprising such derivatives, and methods of inhibiting protein kinase, and methods of treatment comprising administration of such derivatives.
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines
Bahekar, Rajesh H.,Jain, Mukul R.,Jadav, Pradip A.,Prajapati, Vijay M.,Patel, Dipam N.,Gupta, Arun A.,Sharma, Ajay,Tom, Robby,Bandyopadhya, Debdutta,Modi, Honey,Patel, Pankaj R.
, p. 6782 - 6795 (2008/03/28)
In the present investigation, two series of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines (2a-l) and thieno[2,3-b]pyridines (3a-l) were designed as analogs of BL 11282 (1). The in vitro glucose dependent insulinotropic activity of all the test compounds was evaluated using RIN5F cell based assay and all the test compounds showed glucose and concentration dependent insulin secretion. The in vivo antidiabetic activities of most potent compounds from each series (2c and 3c) were assessed in C57BL/6J mice. Compounds 2c and 3c showed dose dependent insulin secretion and significant glucose reduction in vivo. In general, compounds 2c and 3c were found to be equipotent at all the three different doses selected and with respect to BL 11282, both the test compounds were found to be more potent, at all the time points.
