- Preparation methods of 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine
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The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.
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Paragraph 0072-0083
(2021/05/12)
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- Synthesis of N-arylindazole-3-carboxamide and N-benzoylindazole derivatives and their evaluation against α-MSH-stimulated melanogenesis
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We have designed and synthesized twenty-six N-arylindazole-3-carboxamide (3a-p) and N-benzoylindazole (6a-j) derivatives to discover with excellent inhibition activities of α-MSH-stimulated melanogenesis. In the bio evaluation studies of these compounds,
- Arepalli, Sateesh Kumar,Lee, Chaerim,Jung, Jae-Kyung,Kim, Youngsoo,Lee, Kiho,Lee, Heesoon
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supporting information
p. 2604 - 2608
(2019/08/07)
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- 1 - (3 - benzoyl-aminobenzyl) - 1H - indazole - 3 - carboxamides and its preparation method and anti-viral uses (by machine translation)
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The invention relates to a anti-viral inhibitors, in particular, relates to a class of non-nucleoside anti-virus can be used as an inhibitor of the general formula 1 indicated by the 1 - (3 - benzoyl-aminobenzyl) - 1H - indazole - 3 - carboxamides of the organic small molecule compound, and its pharmaceutically acceptable salt or hydrate, its preparation method and its in preparation for treating hepatitis c, hepatitis b, influenza, herpes, viral diseases such as aids in the application of the pharmaceutical, in particular for the preparation of a medicament in the treatment of hepatitis c of the application. Said compound of the invention has the advantages of simple synthesis, easy availability of raw materials, the advantages of low toxicity. (by machine translation)
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Paragraph 0136; 0137; 0138; 0139
(2017/01/17)
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- Development of a potent and selective FLT3 kinase inhibitor by systematic expansion of a non-selective fragment-screening hit
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A non-selective inhibitor (1) of FMS-like tyrosine kinase-3 (FLT3) was identified by fragment screening and systematically modified to afford a potent and selective inhibitor 26. We confirmed that 26 inhibited the growth of FLT-3-activated human acute myeloid leukemia cell line MV4-11. Our design strategy enabled rapid development of a novel type of FLT3 inhibitor from the hit fragment in the absence of target-structural information.
- Nakano, Hirofumi,Hasegawa, Tsukasa,Imamura, Riyo,Saito, Nae,Kojima, Hirotatsu,Okabe, Takayoshi,Nagano, Tetsuo
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supporting information
p. 2370 - 2374
(2016/04/20)
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- Design, synthesis and evaluation of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase
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Human neutrophil elastase (HNE) plays an important role in tumour invasion and inflammation. A series of N-benzoylindazoles was synthesized and evaluated for their ability to inhibit HNE. We found that this scaffold is appropriate for HNE inhibitors and that the benzoyl fragment at position 1 is essential for activity. The most active compounds inhibited HNE activity with IC50 values in the submicromolar range. Furthermore, docking studies indicated that the geometry of an inhibitor within the binding site and energetics of Michaelis complex formation were key factors influencing the inhibitor's biological activity. Thus, N-benzoylindazole derivatives and their analogs represent novel structural templates that can be utilized for further development of efficacious HNE inhibitors.
- Crocetti, Letizia,Giovannoni, Maria Paola,Schepetkin, Igor A.,Quinn, Mark T.,Khlebnikov, Andrei I.,Cilibrizzi, Agostino,Piaz, Vittorio Dal,Graziano, Alessia,Vergelli, Claudia
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p. 4460 - 4472
(2011/09/12)
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- Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H- pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design
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The application of fragment-based screening techniques to cyclin dependent kinase 2 (CDK2) identified multiple (>30) efficient, synthetically tractable small molecule hits for further optimization. Structure-based design approaches led to the identification of multiple lead series, which retained the key interactions of the initial binding fragments and additionally explored other areas of the ATP binding site. The majority of this paper details the structure-guided optimization of indazole (6) using information gained from multiple ligand-CDK2 cocrystal structures. Identification of key binding features for this class of compounds resulted in a series of molecules with low nM affinity for CDK2. Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers.
- Wyatt, Paul G.,Woodhead, Andrew J.,Berdini, Valerio,Boulstridge, John A.,Carr, Maria G.,Cross, David M.,Davis, Deborah J.,Devine, Lindsay A.,Early, Theresa R.,Feltell, Ruth E.,Lewis, E. Jonathan,McMenamin, Rachel L.,Navarro, Eva F.,O'Brien, Michael A.,O'Reilly, Marc,Reule, Matthias,Saxty, Gordon,Seavers, Lisa C. A.,Smith, Donna-Michelle,Squires, Matt S.,Trewartha, Gary,Walker, Margaret T.,Woolford, Alison J.-A.
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supporting information; experimental part
p. 4986 - 4999
(2009/08/16)
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- 1H-INDAZOLE-3-CARBOXAMIDE COMPOUNDS AS MAPKAP KINASE MODULATORS
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The invention provides compounds of the formula: (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a MAPKAP kinase: wherein A is a bond or a group CH2; R1 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; R3, R4, R5 and R6 are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra -Rbwherein Ra is a bond, 0, CO, X1C(X2), C(X2)Xl, X1C(X2)X1, S, SO, S02, NRc, SO2NRc or NRcS02; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; Rc is hydrogen or C1-4hydrocarbyl; and X1 is O, S or NRc and X2 is =O, =S or =NRc.
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Page/Page column 72
(2010/02/10)
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