- BENZOFURAN-BASED N-ACYLHYDRAZONE DERIVATIVES AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A benzofuran-based N-acylhydrazone derivative according to the present invention has an excellent anticancer effect while having low toxicity and excellent solubility, and, thus, a pharmaceutical composition comprising the derivative can be usefully used to prevent or treat a cell proliferative disorder including various cancers. To this end, the present invention provides a compound represented by chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.
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Paragraph 0156-0159
(2021/02/02)
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- Synthesis and Antimicrobial Activities of Novel Quinazolinone Acylhydrazone Derivatives Containing the Indole Moiety
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A series of novel quinazolinone acylhydrazone derivatives containing the indole moiety were designed, synthesized, and evaluated for their inhibition activities against some important phytopathogens in vitro. Antibacterial experiments indicated that some compounds exhibited remarkable inhibition activities against tested bacteria. Especially, the EC50 values of 7a (EC50?=?55.13?μg/mL against Xoo, EC50?=?56.92?μg/mL against Rs) demonstrated the best antibacterial activities against Xoo and Rs than the other compounds, and the control agents Bismerthiazol (EC50?=?89.80?μg/mL against Xoo) and Thiodiazole copper (EC50?=?189.52?μg/mL against Rs), moreover, compound 7o (EC50?=?50.80?μg/mL) displayed the excellent activity against Xac than the control Bismerthiazol (EC50?=?56.92?μg/mL).
- Li, Xiao-Qin,Gan, Yi-Yuan,Meng, Jiao,Li, Wen,Chen, Jie,Qi, Ya-Yun,Tian, Kun,Ouyang, Gui-Ping,Wang, Zhen-Chao
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p. 1382 - 1390
(2018/04/25)
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- Copper-catalyzed Synthesis of N-alkylated 2-(4-substituted-1H-1,2,3-triazol-1-yl)-1H-indole-3-carbaldehyde by Step-wise and One-pot Three-component Huisgen's 1,3-dipolar Cycloaddition Reaction
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An efficient method for the synthesis of N-alkylated 2-(4-substituted-1H-1,2,3-triazol-1-yl)-1H-indole-3-carbaldehyde has been developed starting from oxindole and indole using Huisgen's 1,3-dipolar cycloaddition reaction of organic azides to alkynes. The effect of catalysts and solvent on these reactions has been investigated. Among all these conditions, while using CuSO4·5H2O, DMF was found to be the best system for this reaction. It could also be prepared in a one-pot three-component manner by treating equimolar quantities of halides, azides, and alkynes. The Huisgen's 1,3-dipolar cycloaddition reaction was performed using CuSO4·5H2O in DMF with easy work-up procedure.
- Avula, Vijay Kumar Reddy,Vallela, Swetha,Anireddy, Jaya Shree,Chamarthi, Naga Raju
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p. 3071 - 3076
(2017/10/03)
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- Tandem copper (Cu) catalysed N-arylation-vinylogous nitroaldol condensation of 3,5-disubstituted 4-nitropyrazoles
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A tandem process involving copper catalysed N-arylation and vinylogous nitroaldol condensation is described. The reaction of 3,5-dialkyl substituted 4-nitropyrazoles and ortho-halo substituted (hetero)aryl aldehydes or ketones furnished 3-nitropyrazolo[1,5-a]quinoline and heteroaryl-fused 3-nitropyrazolo[1,5-a]pyridine derivatives in moderate to high yields.
- Obulesu, Owk,Nanubolu, Jagadeesh Babu,Suresh, Surisetti
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supporting information
p. 8232 - 8240
(2015/08/03)
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- Reaction of 2-chloro-1-alkyl-1H-indole-3-carbaldehydes with barbituric acids and 5-methyl-2-phenyl-2,4-dihydropyrazol-3-one. Formation of compound with extremely short intramolecular hydrogen bond in eight-membered pseudocycle
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New indolin-2-one derivatives, containing in its molecules eight-membered pseudo-cycle with unusually short intramolecular hydrogen bond in OHO-bridge have been synthesized by reaction of 2-chloro-1-alkyl-1H-indole-3-carbaldehyde with barbituric acids or 5-methyl-2-phenyl-2,4-dihydropyrazol-3-one. Under the action of amines they undergo fragmentation to 5-aminomethylenebarbituric acids or 4-aminomethylenepyrazolones and 1-alkyl-1,3-dihydroindol-2-ones.
- Suzdalev, Konstantin F.,Babakova, Maria N.,Kartsev, Victor G.,Krasnov, Konstantin A.
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- Substituent-guided switch between C-H activation and decarboxylative cross-coupling during palladium/copper-catalyzed cascade reactions of 2-aminobenzoates with 2-haloarylaldehydes
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Cascade switch: Phenanthridines, pyrazole[4,3-c]quinolines and isocryptolepine were prepared in one step from the Pd/Cu-catalyzed reaction between potassium 2-aminobenzoates and 2-haloarylaldehydes (see scheme). Although the reactions of 2-aminobenzoates proceeded via a cascade imination/C-H functionalization, the reactions of 6-nitro-2-aminobenzoates ensued via a tandem imination/decarboxylative cross-coupling. Copyright
- Bhowmik, Subhendu,Pandey, Garima,Batra, Sanjay
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supporting information
p. 10487 - 10491
(2013/08/23)
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- An efficient one-pot, three-component reaction: Synthesis of complex-annelated α-carbolines via an intramolecular [3+2]-dipolar cycloaddition reaction
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Novel annelated α-carbolines have been synthesized from oxindole using three components in a one-pot procedure involving an intramolecular [3+2]-dipolar cycloaddition reaction of azides to nitriles. Georg Thieme Verlag Stuttgart ? New York.
- Majumder, Swarup,Bhuyan, Pulak J.
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experimental part
p. 1547 - 1550
(2011/08/04)
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- Substituted indoles as inhibitors of poly (ADP-ribose) polymerase (PARP)
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The present invention relates to a series of substituted indole derivatives of the formula I: wherein R, R1, R2, R3, R4, X and Y are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.
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Page/Page column 17
(2010/02/11)
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- Aryllead(IV) reagents in synthesis: formation of the C11 quaternary center of N-methylwelwitindolinone C isothiocyanate.
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The reaction of lead(IV) 4-indolyl triacetate with substituted methyl 2-oxo-1-cyclohexanecarboxylates has been investigated as a route to the natural product N-methylwelsitindolinone C isothiocyanate. Reaction of lead(IV) reagent 18 with beta-ketoester 20 affords the desired coupled material in excellent yield and diastereoselectivity. Reaction: see text.
- Deng,Konopelski
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p. 3001 - 3004
(2007/10/03)
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- Propenone derivatives
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The present invention relates to propenone derivatives represented by the following formula (I): STR1 wherein R1 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, or YR5 (wherein Y represents S or O; and R5 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a substituted or unsubstituted cyclic ether residue); R2 and R3 independently represent hydrogen, lower alkyl, or substituted or unsubstituted aralkyl, or alternatively R2 and R3 are combined to form substituted or unsubstituted methylene or ethylene; R4 represents hydrogen, hydroxy, lower alkyl, substituted or unsubstituted aralkyl, lower alkoxy, substituted or unsubstituted aralkyloxy, or halogen; and X represents substituted or unsubstituted indolyl; or pharmaceutically acceptable salts thereof.
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- ANTAGONISTS, THEIR PREPARATION AND USE
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The present invention relates to therapeutically active non competitive antagonists, acting selectively at the metabotropic glutamate receptor. The novel compounds are useful in treating diseases in the central nervous system by modulating synaptic transmission via the metabotropic glutamate receptor.
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- Tyrosine kinase inhibitors. 6. Structure-activity relationships among N- and 3-substituted 2,2'-diselenobis(1H-indoles) for inhibition of protein tyrosine kinases and comparative in vitro and in vivo studies against selected sulfur congeners
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A small series of 2,2'-diselenobis(1H-indoles) was synthesized as redox- modified congeners of our earlier reported 2,2'-dithiobis(1H-indole) series. Utilizing chemistry similar to that developed earlier for the disulfur series, compounds were made from 2-halogeno-3-indolecarboxylic acid precursors bearing various polar functionality at the C-3 position and small alkyl substituents at the N-1 position of the indole nucleus. Additional compounds were derived from (R)- or (S)-tryptophan via a novel application of diselenium dichloride as an electrophilic source of diselenium, and a much improved process to a 2,2'-dithiobis(1H-indole) congener was developed utilizing disulfur dichloride as a source of disulfur. Against isolated epidermal growth factor receptor (EGFr), platelet-derived growth factor receptor (PDGFr), and v-src tyrosine kinases, compounds in this series displayed broad inhibitory activity with IC50 = 0.9 to > 100 μM vs EGFr, 3.4 to >50 μM vs PDGFr, and 0.4-6.7 μM vsv-src. In general, compounds derived from tryptophan displayed the greatest potency against EGFr and those from 2-halogeno-3-indolecarboxylic acids greater potency against PDGFr and v- src. Enzyme kinetics studies showed that both classes of compounds display primarily noncompetitive inhibition with respect to either ATP or peptide substrate. The sulfhydryl reducing agent dithiothreitol (DTT) caused a general decrease in inhibition of the EGFr and v-src tyrosine kinases by both the diselenium and disulfur series with the reversal of enzyme inhibition occurring less readily within the diselenium series. In whole cell studies, compounds of this class were growth inhibitory against Swiss 3T3 mouse fibroblasts with IC50 values from 0.5 to 19.5 μM, and the observed SAR was different from that of the 2,2'-dithiobis(1H-indoles). A comparative study in the same cell line on the effects of the 2,2'-diselenobis(lH-indole) derived from (R)-tryptophan vs its disulfur congener on growth factor mediated tyrosine phosphorylation showed that this compound significantly inhibited EGFr and PDGFr (in response to its ligand) autophosphorylation with complete suppression at 25 and 5 μM, respectively. Tyrosine phosphorylation of an 85 kDa protein typically phosphorylated in response to bFGF was also exquisitely sensitive to this compound, and it displayed inhibitory effects on DNA, RNA, and protein synthesis at submicromolar concentrations. The disulfur congener exhibited a qualitatively similar pattern; however, its potency was 10-fold less. This same diselenium/disulfur pair was evaluated in vivo against the B16 melanoma, colon carcinoma 26, and M5076 sarcoma murine tumors, and the A431 epidermoid, and C6 glioma human tumor xenografts. At maximum tolerated doses (1.8 and 5.0 mg/kg/injection, respectively), neither the diselenium nor disulfur congener was effective against the C6 glioma when administered intraperitoneally on a d 1-9 schedule. Studies were also carried out against the A431 epidermoid xenograft to evaluate the same pair of compounds via continuous subcutaneous infusion from Alzet miniosmotic pumps. The maximum dose that could be administered daily was limited by compound solubility. Neither compound produced an antitumor effect in a 7-day continuous infusion study. In the 27-day study, the disulfur compound was inactive whereas the diselenium compound produced a 10.8-day growth delay without appreciable treatment related weight loss. The in vitro and in vivo findings offer a mechanistic rationale as to why the 2,2'-diselenobis(1H-indoles) are more potent inhibitors than their disulfur congeners.
- Showalter, H. D. Hollis,Sercel, Anthony D.,Leja, Boguslawa M.,Wolfangel, Craig D.,Ambroso, Linda A.,Elliott, William L.,Fry, David W.,Kraker, Alan J.,Howard, Curtis T.,Lu, Gina H.,Moore, Charles W.,Nelson, James M.,Roberts, Bill J.,Vincent, Patrick W.,Denny, William A.,Thompson, Andrew M.
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p. 413 - 426
(2007/10/03)
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- THIENO[2,3-B-INDOLE DERIVATIVES AND THEIR USE FOR TREATING CENTRAL NERVOUS SYSTEM DISEASES RELATED TO THE METABOTROPIC GLUTAMATE RECEPTOR SYSTEM
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The present invention relates to therapeutically active heterocyclic compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system related to the metabotropic glutamate receptor system.
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- New 5H-1,2,4-triazino[5,6-b]indole and aminoindole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation, anti-hypertensive agents and thromboxane synthetase inhibitors
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This paper reports the synthesis of a series of 5H-1,2,4-triazino[5,6-b]indole 3 and 4, and aminoindole 12-23, derivatives, obtained from isatin 1 and from oxoindole 5, respectively. All the new compounds were studied as antihypertensive agents in spontaneously hypertensive rats (SHR), and as inhibitors of platelet aggregation in guinea pig whole blood, induced by arachidonic acid (AA), adenosin-5'-diphosphate (ADP) or collagen. The most active antiaggregating compounds were also studied as thromboxane A2 synthetase inhibitors.
- Monge,Palop,Ramirez,Font,Fernandez-Alvarez
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p. 179 - 188
(2007/10/02)
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