- 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 0376
(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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- DIAZONIUM-FREE METHOD TO MAKE AN INDAZOLE INTERMEDIATE IN THE SYNTHESIS OF BICYCLIC 5-(TRIFLUORMETHOXY)-1H-3-INDAZOLECARBOXYLIC ACID AMIDES
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The present invention provides novel methods for preparing 5-(trifluoromethoxy)-lH-3- indazolecarboxylic acid (3), which is a useful precursor for the preparation of bicyclic-5- trifluoromethoxy-lH-indazole-S-carboxylic acid amides of Formula (1).Compounds of Formula (1) are active as agonists and partial agonists of the nicotinic alpha-7 receptor and are being studied for their use in the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain, such as for the treatment of Alzheimer's disease and schizophrenia, as well as other psychiatric and neurological disorders.The present methods are useful for preparing compound (3) on scale up levels
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Page/Page column 20
(2010/04/30)
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- NICOTINIC ALPHA-7 RECEPTOR LIGANDS AND PREPARATION AND USES THEREOF
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The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nAChR), activation of nAChRs, 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 which act as ligands for the α7 nAChR subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 37
(2008/06/13)
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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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