- Electrochemical dehydrogenative C-N coupling of hydrazones for the synthesis of 1H-indazoles
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An electrochemical dehydrogenative C-N coupling method has been developed for the synthesis of 1H-indazoles from easily available hydrazones. Various functional groups are compatible with this metal- and oxidant-free protocol which can be carried out on a gram-scale under neutral and mild conditions. This method was applied for the efficient synthesis of anti-tumor compounds. Mechanism studies show that HFIP plays an important role in this transformation which might involve a radical pathway.
- Chen, Na,Chen, Zhenkun,Ye, Zenghui,Zhang, Fengzhi,Zhang, Hong
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supporting information
p. 1463 - 1468
(2022/03/08)
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- Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution
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The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.
- Alam, Ryan M.,Keating, John J.
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supporting information
p. 1939 - 1951
(2021/08/23)
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- Indazole compounds and preparation method and application thereof
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The invention provides indazole compounds and a preparation method and application thereof. A series of completely new small molecule PI3Kdelta inhibitors are designed and synthesized by using indazole as a structural mother nucleus, the PI3Kdelta kinase inhibitory activity test and MV-4-11 cell activity test of the compounds are carried out, and the indazole compounds exhibit better kinase subtype selectivity, and exhibit better in vitro proliferation inhibitory activity against tumor cell lines. The compounds can be used in the preparation of antitumor drugs and in the preparation of activedrugs for inhibiting PI3Kdelta kinase, and a new way is provided for the antitumor drug research. The raw materials are cheap and easy to obtain, the preparation method is simple, and the large-scaleproduction is suitable. The structural formula is as shown in the specification.
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- Preparation method of indazole and application of indazole in medicine synthesis
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The invention belongs to the field of chemicals, and relates to a preparation method of indazole and an application of the indazole in medicine synthesis. The invention discloses a preparation method of indazole and an application of the indazole in synthesizing 1H-indazole-3-carboxylic acid, lonidamine, a compound 8, a compound 9, a compound 10, axitinib, YD-3, YC-1 and similar substances thereof.
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Paragraph 0086; 0087; 0091; 0099; 0100
(2017/04/21)
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- Copper(I) Oxide-Mediated Cyclization of o-Haloaryl N-Tosylhydrazones: Efficient Synthesis of Indazoles
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An efficient synthesis of indazoles from readily accessible E/Z mixtures of o-haloaryl N-tosylhydrazones has been developed. The thermo-induced isomerization of N-tosylhydrazones is discussed. A series of valuable indazole derivatives are prepared in good yields, and the method has been successfully applied to the synthesis of the bioactive compounds, lonidamine, AF-2785, axitinib, YC-1 and YD-3.
- Tang, Meng,Kong, Yuanfang,Chu, Bingjie,Feng, Dan
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supporting information
p. 926 - 939
(2016/04/05)
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- BICYCLIC HETEROARYL INDOLE ANALOGUES USEFUL AS ROR GAMMA MODULATORS
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The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X, X1, M, R2, R3, R4, R5, m, n, and p are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, neurodegenerative diseases and cancer.
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Page/Page column 46; 47
(2015/06/25)
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- One-pot synthesis of novel 3,5-disubstituted-1,2,4-oxadiazoles from indazole carboxylic acid esters and amidoximes
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An efficient and high-yielding one-pot synthesis of 3,5-disubstituted-1,2, 4-oxadiazoles from indazole carboxylic acid methyl esters and amidoximes is described. In this study a series of novel 3,5-disubstituted-1,2,4-oxadiazoles (3a-d), (4a-d), (5a-d), (6a-d), (7a-d) were synthesized using amidoximes 2a-d and indazole carboxylic acid esters (3-6).
- Swamy, Udutha Kumara,Mohan, H. Rama,Prasad, U. Viplava,Suresh,Kumar, T. Laxmi
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p. 1921 - 1930
(2014/06/09)
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- METHODS FOR THE PREPARATION OF N-(S)-1-AZABICYCLO[2.2.2]OCT-3-YL-1H-INDAZOLE-3-CARBOXAMIDE HYDROCHLORIDE SALT
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The present invention provides novel methods for preparing N—(S)-1-azabicyclo[2.2.2]oct-3-yl-1H-indazole-3-carboxamide HCl salt 1, a nicotinic α-7 receptor ligand, that are useful for the scaled-up preparation of compound 1. Compound 1 is useful 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.
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- METHODS FOR THE PREPARATION OF INDAZOLE-3-CARBOXYLIC ACID AND N-(S)-1-AZABICYCLO[2.2.2]OCT-3-YL-1H-INDAZOLE-3-CARBOXAMIDE HYDROCHLORIDE SALT
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The present invention provides novel methods for preparing indazole-3-carboxylic acid 2, a key starting material for the manufacture of agonists or partial agonists of the nicotinic α-7 receptor, such as N—(S)-1-azabicyclo[2.2.2]oct-3-yl-1H-indazole-3-carboxamide HCl salt 13. Nicotinic α-7 receptor agonists and partial agonists are being useful 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 indazole-3-carboxylic acid on scaled-up levels.
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- 1H-INDAZOLES, BENZOTHIAZOLES, 1,2-BENZOISOXAZOLES, 1,2-BENZOISOTHIAZOLES, AND CHROMONES 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 (indazoles and benzothiazoles), 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 62-63
(2008/06/13)
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- Antifungal and/or antiparasitic pharmaceutical composition and novel indole derivatives as active principle of such a composition
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The present invention relates to novel indole derivatives, their method of preparation and their pharmacological activity as antimycotic and/or antiparasitic compounds.
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Page/Page column 28
(2010/02/06)
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- Blockade of voltage dependent sodium channels
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Compounds of formula (1), and pharmaceutically acceptable salts thereof, are capable of blockading voltage-dependent sodium channels and are useful in particular, in treating glaucoma and multiple sclerosis.
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- VLA-4 INHIBITORS
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The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
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- DERIVATIVES OF AMIDE ANALOGS OF CERTAIN METHANO BRIDGED QUINOLIZINES
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This invention relates to novel amide derivatives of certain 2, 6-methano-2H-quinolizine-type compounds, to the intermediates and processes for their preparation, to their ability to antagonize the effects of serotonin at the 5HT 3 receptors, and to their end-use application in the treatment of chemotherapeutically-induced nausea and vomiting, as anti-anxiety agents, in the symptomatic treatment of pain associated with migraine, as anti-arrhythmic agents, in the treatment of cognitive disorders, in treating hallucinatory endogenous psychoses of the type manifested in patients suffering from schizophrenia, and mania, in the treatment of glaucoma, for stimulating gastric motility, to combat drug abuse, to treat sleep apnea and to treat irritable bowel syndrome.
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- Practical synthesis of 1H-indazole-3-carboxylic acid and its derivatives
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A practical and convenient synthesis of 1H-indazole-3-carboxylic acid and its amide and ester derivatives from the corresponding derivatives of 2-nitrophenylacetic acid was described.
- Yoshida, Toyokichi,Matsuura, Noriyasu,Yamamoto, Katsuhisa,Doi, Masahiro,Shimada, Kanji,Morie, Toshiya,Kato, Shiro
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p. 2701 - 2712
(2007/10/03)
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- Synthesis and evaluation of heterocyclic carboxamides as potential antipsychotic agents
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Heterocyclic analogues of 1192U90, 2-amino-N-(4-(4-(1,2-benzisothiazol- 3-yl)-1-piperazinyl)-butyl)benzamide hydrochloride (1), were prepared and evaluated as potential antipsychotic agents. These analogues were evaluated in vitro for their binding to the dopamine D2, serotonin 5-HT2, and serotonin 5-HT(1a) receptors and in vivo for their ability to antagonize the apomorphine-induced climbing response in mice. Nine different types of heterocyclic carboxamides were studied in this investigation (i.e., pyridine- , thiophene-, benzothiophene-, quinoline-, 1,2,3,4-tetrahydroquinoline-, 2,3- dihydroindole-, indole-, benzimidazole-, and indazolecarbox-amides). Two derivatives exhibited potent in vivo activities comparable to 1: 3-amino-N- (4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2-pyridinecarboxamide (16) and 3-amino-N-(4(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-2- thiophenecarboxamide (29). Furthermore, these derivatives were found to be much less active in behavioral models predictive of extrapyramidal side effects than in the mouse climbing assay, which predicts antipsychotic activity. Carboxamides 16 and 29 were selected for further evaluation as potential backup compounds to 1.
- Norman, Mark H.,Navas III, Frank,Thompson, James B.,Rigdon, Greg C.
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p. 4692 - 4703
(2007/10/03)
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- An Improved Synthesis of Indazole-3-carboxylic Acid
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A new and efficient synthesis of indazole-3-carboxylic acid is reported.The method consists in reacting β-acetylphenylhydrazine with chloral hydrate and hydroxylamine hydrochloride in acidic medium to afford N-acetylaminoisonitrosoacetanilide which, in turn, is converted into the title compound by treatment with sulphuric acid.
- Ferrari, Marinella,Ripa, Alberto,Ripa, Giorgio,Sisti, Massimo
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p. 531 - 532
(2007/10/02)
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