- Design, synthesis and biological evaluation of a novel series of indole-3-carboxamide derivatives for cancer treatment as EGFR inhibitors
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Background: As reported EGFR is a sialoglycoprotein with tyrosine kinase activity involved in control of cellular survival, multiplication, differentiation and metastasis. Dysregulation or aberrant expression of EGFR has been implicated in cell transformation and having oncogenic roles in a number of human cancers. Therefore EGFR has become a significant target for developing targeted therapy for cancer. Methods: A novel series of indole-3-carboxamide derivatives as EGFR inhibitors were designed, synthesized and evaluated for the anticancer activity in vitro against three EGFR high-expressed cancer cell lines (A549, HeLa, and SW480), one EGFR low-expressed cell line (HepG2) and one human liver normal cell line (HL7702) by MTT assay. Results: The target compounds 6c, 6f, 6i, 6j, 6l, 6r, 6u and 6x exhibited potent anticancer activities against the three tested cancer cell lines and weak cytotoxic effects on HepG2, which imply that the target compounds are probably effective in inhibiting EGFR. And they also did not show measurable activities in HL7702, which imply the target compounds are likely to overcome the nonspecific toxicity against normal cells. Particularly, the target compound 6x indicated equal to the positive control erlotinib. In addition, molecular docking studies demonstrated the target compound 6x may be the potential inhibitor to EGFR. Conclusion: A new EGFR inhibitor scaffold and a preliminary discussion on their SARs provide promising opportunities to guide further research on indole-3-carboxamide derivatives as novel anticancer agents.
- Zhang, Lan,Deng, Xin-Shan,Meng, Guang-Peng,Zhang, Chao,Liu, Cong-Chong,Chen, Gu-Zhou,Jiang, Xu-Liang,Zhao, Qing-Chun,Hu, Chun
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Read Online
- Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents
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Oxidative stress results in various pathologies and as consequence antioxidant agents have attracted uninterrupted attention. In this paper, a novel series of indole-3-carboxamide derivatives (6a–6l) were designed and synthesized based on the melatonin structure as novel antioxidants. All of them were evaluated for the antioxidant activities in vitro against human neuroblastoma SH-SY5Y cell line using H2O2 radical scavenging assay. The target compounds 6a, 6f and 6i indicated better activities than the positive control, ascorbic acid, and 6a exhibited the best antioxidant activity. In addition, the structure-activity relationships of the target compounds were also preliminarily summarized based on the obtained experimental data.
- Huang, Erfang,Zhang, Lan,Xiao, Chuying,Meng, Guangpeng,Zhang, Bingqi,Hu, Jianshu,Wan, David Chi-Cheong,Meng, Qingguo,Jin, Zhe,Hu, Chun
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Read Online
- Lead derivatization of ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate and 5-bromo-2-(thiophene-2-carboxamido) benzoic acid as FabG inhibitors targeting ESKAPE pathogens
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Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel.
- Varakala, Saiprasad Dasugari,Reshma, Rudraraju Srilakshmi,Schnell, Robert,Dharmarajan, Sriram
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- Nenitzescu Synthesis of 5-Hydroxyindoles with Zinc, Iron and Magnesium Salts in Cyclopentyl Methyl Ether
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In this work, mild Lewis acids and low environmental impact solvents were investigated for Nenitzescu synthesis. Cyclopentyl methyl ether can be used at room temperature in substitution of halogenated solvents with zinc, iron and magnesium salts as homogeneous catalysts to give 5-hydroxyindoles in fair to good yields. The reaction features a straightforward workup and excellent solvent recycle.
- Azzena, Ugo,Beccu, Andrea,Carboni, Silvia,Carraro, Massimo,De Luca, Lidia,Gaspa, Silvia,Livesi, Marco,Pira, Giovanni Michele,Pisano, Luisa,R?mer, Melina,Satta, Giuseppe,Solinas, Angelo,Usala, Elena
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p. 5835 - 5842
(2021/11/17)
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- MUSCARINIC ACETYLCHOLINE RECEPTOR SUBTYPE 4 ANTAGONISTS IN THE TREATMENT OF ANEMIA
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This disclosure generally relates to treating anemias. More specifically, the disclosure relates to use of muscarinic acetylcholine receptor subtype 4 antagonists, such as small molecule compounds, to promote self-renewal of burst forming unit erythroid (BFU-E) cells and treat anemias.
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- Preparation method of arbidol intermediate
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The invention discloses a preparation method of an arbidol intermediate. Ethyl acetoacetate, monomethylamine and p-benzoquinone used as initial raw materials undergo methylation, cyclization, acetylation, bromination and benzene vulcanization to prepare the target compound ethyl 5-hydroxy-6-bromo-2-phenylthiomethyl-1-methylindole-3-carboxylate. The preparation method of the arbidol intermediate issimple and convenient to operate, cheap and easily available in raw materials, high in yield, low in cost, good in quality, environment-friendly, mild in reaction condition, high in safety productioncoefficient and suitable for large-scale industrial production.
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Paragraph 0023; 0024
(2020/07/02)
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- Benzpyrole-3-formamide compound and application thereof
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The invention belongs to the technical field of medicine, and relates to a benzpyrole-3-formamide compound and application thereof. The structural formula of the benzpyrole-3-formamide compound is shown in the description, wherein R1, R2, R3 and R are described in the claim and the description. The benzpyrole-3-formamide compound and acid addition salt applicable to the compound in pharmacy can betaken as an antioxidant to prepare medicines used for treating or preventing related diseases caused by oxidative damage of protein, wherein the related diseases caused by oxidative damage of proteinare Alzheimer's disease, Parkinson's disease, diabetes, chronic renal failure and the like.
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- 5,6-indole dioxane derivatives and preparation method and application thereof
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The invention belongs to the field of drug synthesis, and particularly relates to a 5,6-indolo dioxane derivative and a preparation method and application thereof. The invention provides the 5,6-indolo dioxane derivative and the preparation method and application thereof. The derivative has certain inhibiting effect on HBV and low toxicity, and is expected to be further used for development of drugs for treating diseases caused by HBV infection, especially for preparing of drugs for treating and preventing viral hepatitis B.
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- PYRROLOBENZODIAZEPINE PRODRUGS AND ANTIBODY CONJUGATES THEREOF
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The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.
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Page/Page column 177
(2018/03/06)
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- 5 - Hydroxy indoles containing heterocyclic ring derivative and its use
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The present invention relates to a heterocyclic ring-containing 5-hydroxy indole derivative as represented by formula I, comprising a racemate of the derivative, an optical isomer of same, and a pharmaceutically acceptable salt and/or hydrate thereof, where substituent R1, R2, X, Y, and Z have the meanings as provided in the description. The compound of formula I is applicable in preparing a medicament for treatment and/or prevention of viral infections, and particularly for preparing an anti-hepatitis B virus medicament and anti-influenza virus medicament.
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Paragraph 0197; 0198
(2018/05/03)
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- Indole carboxamide compounds and use thereof
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The invention belongs to the technical field of medicine and relates to indole carboxamide compounds and a use thereof. The indole carboxamide compounds comprise derivatives of indole carboxamide and pharmaceutically acceptable salts thereof. The indole carboxamide compounds have a general formula shown in the description. R1, R2 and R3 are defined in the claims and the specification. The indole carboxamide compounds and pharmaceutically acceptable acid salts can be used as epidermal growth factor tyrosine kinase inhibitors for treatment on epidermal growth factor receptor transfer disorder associated diseases such as small cells lung cancer, squamous cell carcinoma, adenocarcinoma, large cell carcinoma, colorectal cancer, breast cancer, ovarian cancer and renal cell carcinoma.
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- Synthesis of the new ring system 2-oxo-[1,4]oxazino[3,2-e]indole, heteroanalogue of Angelicin
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A convenient synthesis of the 2-oxo-[1,4]oxazino[3,2-e]indole ring system, an heteroanalogue of Angelicin, is reported. Our synthetic approach consisted of the annelation of the oxazine ring on the indole moiety using 4-amino-5-hydroxy indoles as building blocks. The antiproliferative activity of the new compounds either in the dark or under UVA irradiation was investigated.
- Barraja, Paola,Diana, Patrizia,Montalbano, Alessandra,Martorana, Annamaria,Carbone, Anna,Cirrincione, Girolamo
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p. 4182 - 4184
(2009/12/01)
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- 5-HYDROXYINDOLE-3-CARBOXYLATES DERIVATIVES AND THEIR USE
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The present invention relates to 5-hydroxy-indole-3-carboxylate derivatives of formula I , or racemic mixture or optical isomers or pharmaceutically acceptable salts and/or hydrates thereof, wherein: substitutents R 1 , R 2 , Z, X and Y are as defined in the description. The compounds of formula I can be useful for preparation of medicament for treatment and/or prophylaxis of virus infections, especially for preparation of medicament for anti-HBV (Hepatitis B virus) and anti-HIV (Human immunodeficiency virus).
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Page/Page column 12; 16
(2010/11/25)
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- Lewis acid catalyzed Nenitzescu indole synthesis
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A novel method for Lewis acid catalyzed Nenitzescu indole syntheses of 5-hydroxyindoles bearing different substituents in positions 1 (Alk, Bn, Ar), 2 (Me, Et, Ph), and 3 (COOEt, COMe, CONHPh) as well as tricyclic derivatives are reported. The method is simple, rapid, efficient, and allows preparation of hydroxyindoles from 1,4-benzoquinone and enamines in good to excellent yields with the use of low-polar solvents in the presence of weak Lewis acids catalysts. The formation of 5-hydroxyindoles under such mild conditions is explained in terms of a non-redox mechanism.
- Velezheva, Valeriya S.,Kornienko, Albert G.,Topilin, Sergey V.,Turashev, Ascar D.,Peregudov, Alexander S.,Brennan, Patrick J.
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p. 873 - 879
(2007/10/03)
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- Synthesis and pharmacology of benzoxazines as highly selective antagonists at M4 muscarinic receptors
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Previously, we reported on PD 102807 (41) as being the most selective synthetic M4 muscarinic antagonist identified to date. Synthesized analogues of 41 showed no improvement in affinity and selectivity at that time. However, several newly synthesized compounds exhibit a 7-fold higher affinity at M4 receptors and demonstrate a selectivity of at least 100-fold over all other muscarinic receptor subtypes. For example, compound 28 showed an affinity of pKi = 9.00 at M4 receptors and a selectivity of M1/M4 13 183-fold, M2/M4 = 339-fold, M3/M4 = 151-fold, and M5/M4 = 11 220-fold. This high selectivity along with high affinity has not been reported for any synthetic muscarinic antagonist, nor for natural occurring M4 antagonists such as the M4 selective Eastern Green Mamba venom MT3 (M4 pKb = 8.7, M1/M4 = 40-fold, M2/M4 ≥ 500-fold, M3/M4 500-fold, and M5/M4 ≥ 500-fold). Derivative 24, a compound with a high selectivity pattern as well, has been tested for in vivo efficacy. It was able to block the L-3,4-dihydroxyphenylalanine accumulation produced by CI-1017, an M1/M4 selective muscarinic agonist, in the mesolimbic region and striatum, which suggests that 24 is capable of crossing the blood-brain barrier and confirms the pharmacokinetic data obtained on this compound. This is evidence that suggests that agonist-induced increase in catecholamine synthesis observed in these regions is mediated by M4 receptors.
- B?hme, Thomas M.,Augelli-Szafran, Corinne E.,Hallak, Hussein,Pugsley, Thomas,Serpa, Kevin,Schwarz, Roy D.
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p. 3094 - 3102
(2007/10/03)
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