cas 6850-23-3, 1-METHYL-6-NITRO-1H-INDAZOLE

Articles about 6850-23-3Total 26 be found

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AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
Dopaminergic neuronal loss is the main pathological character of Parkinson’s disease (PD). Abnormal tau hyperphosphorylation will lead to dopaminergic neuronal loss. An indazole derivative 6-amino-1-methyl-indazole (AMI) successfully synthesized to inhibit tau hyperphosphorylation may exert a neuroprotective effect. The in vitro study showed that AMI effectively increased cell viability and alleviated the apoptosis induced by MPP+ in SH-SY5Y cells. In addition, AMI treatment significantly decreased the expression of p-tau and upstream kinases GSK-3β. In the MPTP-induced PD mice models, we found AMI apparently preserved dopaminergic neurons in the substantia nigra and improved the PD behavioral symptoms. Our results demonstrate that AMI exerts a neuroprotective effect by inhibiting tau hyperphosphorylation, representing a promising new candidate for PD treatment.
Mao, Zhang,Wen-ting, Zhu,Hai-tao, Wang,Hui, Yu,Shi-yi, Lan,Jiang-ping, Xu,Wen-ya, Wang
(2020)
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ARYL-PHOSPHORUS-OXYGEN COMPOUND AS EGFR KINASE INHIBITOR
Disclosed is a class of new aryl-phosphorus-oxygen compounds as shown in formula (I) as EGFR kinase inhibitors, and pharmaceutically acceptable salts thereof.
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Paragraph 0306; 0307

(2020/06/16)

Discovery of 1-(1H-indazol-4-yl)-3-((1-phenyl-1H-pyrazol-5-yl)methyl) ureas as potent and thermoneutral TRPV1 antagonists
A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure–activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Among them, the antagonists 26, 50 and 51 displayed highly potent antagonism with Ki(CAP) = 0.4–0.5 nM. Further, in vivo studies in mice indicated that these derivatives both antagonized capsaicin induced hypothermia, consistent with their in vitro activity, and themselves did not induce hyperthermia. In the formalin model, 51 showed anti-nociceptive activity in a dose-dependent manner.
Kang, Jin Mi,Kwon, Sun Ok,Ann, Jihyae,Blumberg, Peter M.,Ha, Heejin,Yoo, Young Dong,Frank-Foltyn, Robert,Lesch, Bernhard,Bahrenberg, Gregor,Stockhausen, Hannelore,Christoph, Thomas,Lee, Jeewoo
(2020/10/06)

Palladium-Catalyzed Oxidative Arylation of 1H-Indazoles with Arenes
A simple method for the direct Pd(OAc)2-catalyzed oxidative arylation of inactivated 1H-indazole derivatives with simple arenes is reported. This method exhibits good reaction efficiency and good functional-group tolerance. Using the developed method, 28 arylated products were prepared in yields up to 80 %.
Gambouz, Khadija,Abbouchi, Abdelmoula El,Nassiri, Sarah,Suzenet, Franck,Bousmina, Mostapha,Akssira, Mohamed,Guillaumet, Gérald,El Kazzouli, Sa?d
supporting information
p. 7435 - 7439
(2020/11/30)

Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents
In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent.
Anh, Le Viet,Hai, Dinh Thi Thanh,Han, Byung Woo,Hien, Tran Thi Thu,Hoang, Ngo Xuan,Hoang, Van-Hai,Long, Nguyen Huu,Luu, Hung N.,Luu, Thi-Thu-Trang,Ngo, Son Tung,Ngo, Thien,Nguyen, Thanh Xuan,Nguyen, Yen Thi Kim,Tran, Phuong-Thao,Van Hieu, Duong
p. 45199 - 45206
(2020/12/30)

THERAPEUTIC INDAZOLES
The invention provides compounds of formula (I): and salts thereof wherein R1-R5 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).
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Page/Page column 25

(2019/03/17)

New nitroindazolylacetonitriles: Efficient synthetic access: Via vicarious nucleophilic substitution and tautomeric switching mediated by anions
New N-Alkyl-nitroindazolylacetonitriles were efficiently obtained via vicarious nucleophilic substitution of N-methyl-nitroindazoles with 4-chlorophenoxyacetonitrile. All compounds were fully characterized by NMR and mass spectroscopy techniques and the structures of some of them were additionally confirmed by X-ray diffraction analysis data. Tautomeric switching was observed in this series of nitroindazolylacetonitriles upon addition of basic anions followed by UV-Vis spectrophotometric and 1H-NMR titrations. The formation of tautomeric species induced by anionic species was endorsed by Density Functional Theory calculations.
Eddahmi, Mohammed,Moura, Nuno M. M.,Bouissane, Latifa,Gamouh, Ahmed,Faustino, Maria A. F.,Cavaleiro, José A. S.,Paz, Filipe A. A.,Mendes, Ricardo F.,Lodeiro, Carlos,Santos, Sérgio M.,Neves, Maria G. P. M. S.,Rakib, El Mostapha
p. 14355 - 14367
(2019/09/30)

Synthesis and Some Transformations of 7-(Fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]benzothiazole
N-Methylation of 5-nitro-1H-indazole in a KOH–DMSO system resulted in a mixture of 1-methyl-5(6)-nitroindazoles in a ratio of 1: 2. Reduction of the isomers with tin in concentrated hydrochloric acid afforded pure 1-methyl-1H-indazole-6-amine. Condensation of the latter with furoyl chloride in 2-propanol yielded N-(1-methylindazol-6-yl)furan-2-carboxamide, treatment of which with an excess of P2S5 in anhydrous pyridine gave the corresponding carbothioamide. 7-(Fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]benzothiazole was synthesized by Jacobson oxidation of N-(1-methylindazol-6-yl) furan-2-carbothioamide with potassium ferricyanide in an alkaline medium. Some transformations of 7-(fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]- benzothiazole such as formylation and acylation were performed.
El’chaninov,Aleksandrov,Stepanov
p. 425 - 429
(2018/04/24)

Wnt signal pathway inhibitor and use thereof
The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.
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Paragraph 0047; 0193-0196

(2017/08/10)

Indazole derivative as well as preparation method and application thereof
The invention relates to an indazole derivative. The molecular structure of the derivative is as shown in the following formula (I). The compound disclosed by the invention has outstanding effects of inhibiting the activity of tau proteins, reducing the phosphorylation level of the tau proteins, resisting neuronal apoptosis and preventing and treating neurodegenerative diseases.
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Paragraph 0013; 0025

(2017/06/13)

One-pot synthesis of new 6-pyrrolyl-N-alkyl-indazoles from reductive coupling of N-alkyl-6-nitroindazoles and 2,5-hexadione
One-pot synthesis of 6-pyrrolyl-N-alkyl-indazoles by the reductive coupling of N-alkyl-6-nitroindazoles and 2,5-hexadione was investigated in the presence of different reducing agents (SnCl2/AcOH and In/AcOH in THF). Indazoles 5a-h and 6a-h wer
El Ghozlani, Mohamed,Chicha, Hakima,Abbassi, Najat,Chigr, Mohamed,El Ammari, Lahcen,Saadi, Mohamed,Spinelli, Domenico,Rakib, El Mostapha
supporting information
p. 113 - 117
(2015/12/23)

HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.
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Paragraph 000413

(2016/05/02)

Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors
The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chemical, plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.
Dong, Yan,Li, Kehuang,Xu, Zhixiang,Ma, Haikuo,Zheng, Jiyue,Hu, Zhilin,He, Sudan,Wu, Yiyuan,Sun, Zhijian,Luo, Lusong,Li, Jiajun,Zhang, Hongjian,Zhang, Xiaohu
p. 6855 - 6868
(2015/11/11)

Palladium-catalyzed direct C7-arylation of substituted indazoles
A novel direct C7-arylation of indazoles with iodoaryls is described using Pd(OAc)2 as catalyst, 1,10-phenanthroline as ligand, and K 2CO3 as base in refluxing DMA. Direct C7-arylation of 3-substituted 1H-indazole containing an EWG on the arene ring gave the expected products in good isolated yields. In addition, a one-pot Suzuki-Miyaura/ arylation procedure leading to C3,C7-diarylated indazoles has been developed.
Naas, Mohammed,El Kazzouli, Sa?d,Essassi, El Mokhtar,Bousmina, Mosto,Guillaumet, Gérald
p. 7286 - 7293
(2014/09/16)

THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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Paragraph 0608; 0609; 0610

(2015/01/06)

Structure-activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template
In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-Aβ and Aβ plaques in cells and transgenic animals.
Lee, Jeewoo,Tran, Phuong-Thao,Hoang, Van-Hai,Thorat, Shivaji A.,Kim, Sung Eun,Ann, Jihyae,Chang, Yu Jin,Nam, Dong Woo,Song, Hyundong,Mook-Jung, Inhee,Lee, Jiyoun
p. 3821 - 3830
(2013/07/19)

Regioselective methylation of indazoles using methyl 2,2,2- trichloromethylacetimidate
An efficient and regio selective synthesis of substituted 2-methyl-2H-indazoles using a methyl 2,2,2-trichloroacetimidate is described.
Baddam, Sudhakar Reddy,Uday Kumar,Panasa Reddy,Bandichhor, Rakeshwar
supporting information
p. 1661 - 1663
(2013/03/29)

8 - SUBSTITUTED 2 -AMINO - [1,2,4] TRIAZOLO [1, 5 -A] PYRAZINES AS SYK TRYROSINE KINASE INHIBITORS AND GCN2 SERIN KINASE INHIBITORS
Compounds of the formula I in which R1, R2 and R4 have the meanings indicated in Claim 1, are inhibitors of Syk, and can be employed, inter alia, for the treatment of cancer, rheumatoid arthritis and / or systemic lupus
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Page/Page column 101

(2013/09/12)

THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
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Page/Page column 87; 88

(2013/07/19)

ISOINDOLINE COMPOUNDS FOR THE TREATMENT OF SPINAL MUSCULAR ATROPHY AND OTHER USES
Disclosed is a compound of Formula (I) in which W and R1-R6 are defined herein. Also disclosed is a method of treating spinal muscular atrophy, as well as methods of using such compounds to increase SMN expression, increase EAAT2 expression, or increase the expression of a nucleic acid that encodes a translational stop codon introduced directly or indirectly by mutation or frameshift.
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Page/Page column 84

(2009/05/29)

An expedient, regioselective synthesis of novel 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]- and -[4,5-g]indazoles and their anticancer potential
Several novel 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]- and -[4,5-g]indazoles and their 6-alkyl and 8-alkyl derivatives have been synthesised in high overall yields starting from 5-nitro and 6-nitroindazoles in a three-step route involving the regioselective cyclisation of thioureidoindazoles and indazolyl dithiocarbamates as the key steps. Some assorted thiazoloindazoles have been screened for anticancer properties, which demonstrated the anticancer potential of at least one product, justifying its further follow-up.
Chakrabarty, Manas,Kundu, Taraknath,Arima, Shiho,Harigaya, Yoshihiro
p. 6711 - 6723
(2008/12/20)

Reduction of nitroindazoles: Preparation of new amino and chloroamino derivatives
The synthesis of chloroaminoindazoles by the reduction of the nitro group of indazoles using stannous chloride in alcoholic acid solution is reported. Using catalytic hydrogenation with palladium the expected reduction to amino-indazoles occur.{A figure is presented}. Indazole Nitro Reduction Chlorination Aminochloroindazole Heterocycle.
Miloudi, Abdellah,El Abed, Douniazed,Boyer, Gerard,Galy, Jean-Pierre
p. 2595 - 2605
(2008/02/04)

A synthesis of 9-methoxy-1-methyl-1H,6H-pyrazolo[4,3-c]carbazole
The synthesis of 9-Methoxy-1-methyl-1H,6H-pyrazolo[4,3-c]carbazole is reported in four steps from 6-nitroindazole. Palladium acetate mediated cyclization gave only the 'bent' tetracyclic derivative.
Morel, Sandrine,Boyer, Gerard,Coullet, Fabien,Galy, Jean-Pierre
p. 2443 - 2447
(2007/10/03)

SYNTHESIS OF SUBSTITUTED PYRAZOLO- AND PYRAZOLOPHENOTHIAZINE DERIVATIVES
The synthesis of new pyrazolo- and phenothiazines by the Bernthsen thionation of N-arylindazoles obtained using organometalic compounds is reported.
Boyer, Gerard,Galy, Jean Pierre,Barbe, Jacques
p. 487 - 496
(2007/10/02)

Synthesis of Pyrazoloacridin-9(10H)-ones
Eight pyrazoloacridin-9(10H)-ones were prepared in a three step procedure from 5- and 6-nitroindazoles.Palladium catalysed hydrogenation of nitroindazoles afforded the corresponding 5- and 6-aminoindazoles.These, in turn, reacted with o-chlorobenzoic acid under the conditions of the Ullman reaction to give anthranilic acids.Cyclisation of these acids by means of sulfuric acid led to the title compounds.If phosphoryl chloride was used, instead of sulfuric acid, a 9-chloroacridine derivative was obtained.All the compounds were characterised by 1H NMR spectroscopy.
Boyer, Gerard,Galy, Jean-Pierre,Faure, Robert,Elguero, Jose,Barbe, Jacques
p. 2601 - 2615
(2007/10/02)

SYNTHESIS OF 5-HYDROXY-4-NITROSOBENZOTRIAZOLES AND 6-HYDROXY-7-NITROSO-INDAZOLES AND THEIR SPLITTING INTO β-TRIAZOLYL- AND β-PYRAZOLYLACRYLIC ACIDS
5-Hydroxy-4-nitrosobenzotriazoles and 6-hydroxy-7-nitrosoindazoles were synthesized.By the action of benzenesulfonyl chloride in an alkaline medium, only 5-hydroxy-4-nitroso-2-phenyl-benzotriazole and 1-methyl-6-hydroxy-7-nitrosoindazole split into 5-carb
Stankyavichyus, A. P.,Terent'ev, P. B.,Bolotin, V. A.,Lashin, V. V.,Rakhimi, I. M.
p. 403 - 409
(2007/10/02)