- ANTICANCER AGENT
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An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6alkyl group and the like; R4 represents hydrogen atom, a C1-6alkyl group, a C1-6alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; .... represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6alkyl group and the like; R8 represents hydrogen atom, a C1-6alkyl group and the like; A represents -O-, -S-, or - CH2-; D represents -C= or -N=; X represents methylene group, -O-, or -CO-; Q represents -N= or -C(R8)=; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.
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Paragraph 0370
(2013/03/26)
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- Optimization of N-benzoylindazole derivatives as inhibitors of human neutrophil elastase
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Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease selectivity, and stability compared to our previous leads. Introduction of a variety of substituents at position 5 of the indazole resulted in the potent inhibitor 20f (IC50 ~10 nM) and modifications at position 3 resulted the most potent compound in this series, the 3-CN derivative 5b (IC50 = 7 nM); both derivatives demonstrated good stability and specificity for HNE versus other serine proteases. Molecular docking of selected N-benzoylindazoles into the HNE binding domain suggested that inhibitory activity depended on geometry of the ligand-enzyme complexes. Indeed, the ability of a ligand to form a Michaelis complex and favorable conditions for proton transfer between Hys57, Asp102, and Ser195 both affected activity.
- Crocetti, Letizia,Schepetkin, Igor A.,Cilibrizzi, Agostino,Graziano, Alessia,Vergelli, Claudia,Giomi, Donatella,Khlebnikov, Andrei I.,Quinn, Mark T.,Giovannoni, Maria Paola
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p. 6259 - 6272
(2013/09/02)
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- New practical access to 2-azatryptophans and dehydro derivatives via the Wittig-Horner reaction
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The Wittig-Horner reaction of protected 3-formylindazoles 1 with (±)-N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester 2 has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives. The preparation of 5-br
- Crestey, Fran?ois,Collot, Valérie,Stiebing, Silvia,Lohier, Jean-Fran?ois,Santos, Jana Sopkova-de Oliveira,Rault, Sylvain
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p. 2457 - 2460
(2007/10/03)
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- Design and synthesis of a new indazole library: direct conversion of?N-methoxy-N-methylamides (Weinreb amides) to 3-keto and 3-formylindazoles
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Nucleophilic addition of Grignard or lithiated reagents on the new Weinreb amides 3 and 4 afforded efficiently the corresponding ketones and allowed the design and synthesis of a new indazole library. These 3-ketoindazoles were obtained by a direct and or
- Crestey, Fran?ois,Stiebing, Silvia,Legay, Rémi,Collot, Valérie,Rault, Sylvain
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p. 419 - 428
(2007/10/03)
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- Indoles, 1h-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
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The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (indazoles and benzothiazoles), which act as ligands for the α7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 39
(2008/06/13)
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- The serotonin 5-HT4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists.
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A number of substituted indole carbazimidamides were prepared and evaluated as 5-HT4 receptor agonists by using the isolated field-stimulated guinea pig ileum preparation. Their selectivity for the 5-HT4 receptor was established by examining their affinity for other 5-HT receptors using radioligand-binding techniques. Several selective and highly potent full as well as partial agonists emerged from this study. For example, 1b,d were found to be the most potent, full 5-HT4 receptor agonist described so far (EC50 = 0.5 and 0.8 nM, respectively), being 6 and 4 times more potent than serotonin itself. On the other hand, 5b and 1h appeared as partial 5-HT4 receptor agonists in the nonstimulated guinea pig ileum preparation with potencies, evaluated against serotonin action, respectively similar (5b, Ki = 12 nM) to and 300-fold higher (1h, Ki = 0.04 nM) than serotonin.
- Buchheit,Gamse,Giger,Hoyer,Klein,Kloeppner,Pfannkuche,Mattes
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p. 2331 - 2338
(2007/10/02)
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