- A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids
-
A novel method for the synthesis of 3-monohalooxindoles by acidolysis of isatin-derived 3-phosphate-substituted oxindoles with haloid acids was developed. This synthetic strategy involved the preparation of 3-phosphate-substituted oxindole intermediates and SN1 reactions with haloid acids. This new procedure features mild reaction conditions, simple operation, good yield, readily available and inexpensive starting materials, and gram-scalability.
- Huang, Tiao,Kong, Dulin,Li, Yue,Liu, Li,Wu, Mingshu
-
p. 2321 - 2328
(2021/09/22)
-
- A Unified Catalytic Asymmetric (4+1) and (5+1) Annulation Strategy to Access Chiral Spirooxindole-Fused Oxacycles
-
A unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides has been achieved in the presence of a chiral phase-transfer catalyst (PTC). This general strategy utilizes peroxides as unique bielectrophilic four- or five-atom synthons to participate in the C?C and the subsequent umpolung C?O bond-forming reactions with one-carbon unit nucleophiles, thus providing a distinct method to access the valuable chiral spirooxindole-tetrahydrofurans and -tetrahydropyrans with good yields and high enantioselectivities under mild conditions. DFT calculations were performed to rationalize the origin of high enantioselectivity. The gram-scale syntheses and synthetic utility of the resultant products were also demonstrated.
- Gao, Min,Gong, Xiangnan,Hu, Lin,Luo, Yanshu,Xia, Yuanzhi,Xu, Qianlan,Zhao, Yukun
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p. 19813 - 19820
(2021/08/03)
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- METHOD FOR PRODUCING LACTAM COMPOUND, AND LACTAM COMPOUND PRODUCED THEREBY
-
The present invention relates to a method for producing a lactam compound from dioxazolone in the presence of a catalyst having a particular ligand, and to a lactam compound produced thereby, and can produce a lactam compound with excellent selectivity and an excellent yield by using the combination of a starting material having a particular functional group and a particular catalyst having a particular ligand.
- -
-
Paragraph 0174-0175; 0186
(2020/11/30)
-
- Synthesis of Lactams via Ir-Catalyzed C-H Amidation Involving Ir-Nitrene Intermediates
-
x-membered lactams were synthesized via either an amidation of sp3 C-H bonds or an electrophilic substitution of arenes via Ir-nitrene intermediates. With the employment of a readily available iridium catalyst in dichloromethane or hexafluoro-2-propanol, a wide range of lactams were synthesized in good to excellent yields with high selectivity.
- Li, Xiaoxun,Liu, Jitian,Tang, Weiping,Wang, Shuojin,Ye, Wenjing,Zheng, Junrong
-
-
- Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation
-
A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.
- Henry, Martyn C.,Senn, Hans Martin,Sutherland, Andrew
-
p. 346 - 364
(2019/01/08)
-
- Revisiting Arene C(sp2)?H Amidation by Intramolecular Transfer of Iridium Nitrenoids: Evidence for a Spirocyclization Pathway
-
Two mechanistic pathways, that is, electrocyclization and electrophilic aromatic substitution, are operative in most intramolecular C?H amination reactions proceeding by metal nitrenoid catalysis. Reported here is an alternative mechanistic scaffold leading to benzofused δ-lactams selectively. Integrated experimental and computational analysis revealed that the reaction proceeds by a key spirocyclization step followed by a skeletal rearrangement. Based on this mechanistic insight, a new synthetic route to spirolactams has been developed.
- Hwang, Yeongyu,Park, Yoonsu,Kim, Yeong Bum,Kim, Dongwook,Chang, Sukbok
-
p. 13565 - 13569
(2018/09/25)
-
- Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts
-
Intramolecular insertion of met al nitrenes into carbon-hydrogen bonds to form γ-lactam rings has traditionally been hindered by competing isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C-H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding γ-lactams via sp3 and sp2 C-H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.
- Hong, Seung Youn,Park, Yoonsu,Hwang, Yeongyu,Kim, Yeong Bum,Baik, Mu-Hyun,Chang, Sukbok
-
p. 1016 - 1021
(2018/03/09)
-
- Synthesis and Reactivity of 3,3-Diazidooxindoles
-
The synthesis of previously unknown 3,3-diazidooxindoles as synthetically useful derivatives of isatins was accomplished through the direct oxidative diazidation of 2-oxindoles. The method yielded the diazido compounds from the starting oxindoles under mild and simple conditions with NaN3 and iodine, in good yields. The notable reactivity of this new class of compounds toward primary and secondary nucleophilic amines is also described, which gives access to either 4-imino-3,4-dihydroquinazolin-2(1H)-one derivatives or cyanophenylureas.
- Holzschneider, Kristina,Mohr, Fabian,Kirsch, Stefan F.
-
supporting information
p. 7066 - 7070
(2018/11/24)
-
- Synthesis of novel 3-(benzothiazol-2-ylmethylene)indolin-2-ones
-
A mild method for the synthesis of 3-(benzothiazol-2-ylmethylene)indolin-2-ones via the aldol condensation of substituted indolin-2-ones and benzothiazole-2-carbaldehyde is described. This new procedure has significant advantages, such as mild conditions, high yields and simple work-up.
- Zhang, Chao,Xu, Juan,Zhao, Xinyu,Kang, Congmin
-
p. 537 - 540
(2017/10/03)
-
- A Benzisoelenazolone modified pyrrole methyl ester substituted indole ketone compound and use thereof
-
The invention discloses a benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound and a use thereof. The invention depends on and claims the priority of a Chinese patent application 201110105248.0 submitted on April 26, 2011. Through reference, all contents of the Chinese patent application 201110105248.0 are incorporated into the invention. The benzisoselenazolone-modified pyrrolyl formate-substituted indolone compound is shown in the general formula I. The 2-indolone compound provided by the invention has excellent antitumor activity and can be widely used for preparation of antitumor drugs.
- -
-
Paragraph 0117-0118; 0187-0189
(2016/10/08)
-
- Palladium-Catalyzed C-H Activation and Cyclization of Anilides with 2-Iodoacetates and 2-Iodobenzoates: An Efficient Method toward Oxindoles and Phenanthridones
-
A concise approach to the synthesis of oxindoles and phenanthridones from anilides is described. In the presence of catalytic amount of Pd(OAc)2, 2-iodoacetates and 2-iodobenzoates can be used to functionalize ortho C-H bond of anilides, which subsequently undergo intramolecular cyclization to give the products. A possible reaction mechanism that involves a PdII/PdIV catalytic cycle is proposed with the support of detailed mechanistic studies.
- Gandeepan, Parthasarathy,Rajamalli, Pachaiyappan,Cheng, Chien-Hong
-
p. 1872 - 1879
(2016/06/15)
-
- A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: Construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters
-
A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied.
- Gui, Yong-Yuan,Yang, Jian,Qi, Liang-Wen,Wang, Xiao,Tian, Fang,Li, Xiao-Nian,Peng, Lin,Wang, Li-Xin
-
p. 6371 - 6379
(2015/06/08)
-
- Indolinone based LRRK2 kinase inhibitors with a key hydrogen bond
-
The most prevalent leucine-rich repeat kinase 2 (LRRK2) mutation G2019S is associated with Parkinson's disease (PD). It enhances kinase activity and has been identified in both familial and sporadic cases. Kinase activity was reported to be required for LRRK2 mutants to exert their toxic effects. Hence LRRK2 kinase inhibition may be a promising therapeutic target for PD. Here we report on the discovery and characterization of indolinone based LRRK2 inhibitors. Indolinone 15b, the most potent and selective inhibitor of the present series, is characterized by an IC50of 15 nM against wild-type LRRK2 and 10 nM against the LRRK2 G2019S mutant, respectively. Compound 15b was further evaluated in a kinase panel including 46 human protein kinases and in a zebrafish embryo phenotype assay, which enabled toxicity determination in whole organisms.
- G?ring, Stefan,Taymans, Jean-Marc,Baekelandt, Veerle,Schmidt, Boris
-
supporting information
p. 4630 - 4637
(2015/02/05)
-
- Synthesis, structure, and properties of new spirooxindolodibenzodiazepine derivatives
-
An acid-catalyzed reaction of 3-(2-aminophenylamino)-5,5- dimethylcyclohexen-1-one with isatines leads to the formation of the earlier undescribed 3,3-dimethyl-2,3,4,5,10,11- hexahydrospiro[1H-dibenzo[b,e][1,4] diazepine-11,3-2H-indole]-1,2-dione derivati
- Orlova,Ukhin,Suponitskii,Shepelenko,Belousova,Borodkin,Popova
-
p. 1409 - 1416
(2014/05/06)
-
- Efficient copper-catalyzed intramolecular N-arylation for the synthesis of oxindoles
-
An efficient copper-catalyzed intramolecular N-arylation was performed by using substituted 2-(2-bromoaryl)acetamide with a small amount of Cu 2O and benzene-1,2-diamine as catalytic system under aerobic conditions, which provided good to excellent yields of oxindoles with tolerance of a wide variety of substrates.
- Jhan, Yu-Huei,Kang, Ting-Wei,Hsieh, Jen-Chieh
-
p. 1155 - 1159
(2013/03/13)
-
- Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis
-
A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively.
- Zhong, Ye,Xue, Mengzhu,Zhao, Xue,Yuan, Jun,Liu, Xiaofeng,Huang, Jin,Zhao, Zhenjiang,Li, Honglin,Xu, Yufang
-
p. 1724 - 1734
(2013/05/08)
-
- Synthesis, in silico, in vitro, and in vivo investigation of 5-[ 11C]methoxy-substituted sunitinib, a tyrosine kinase inhibitor of VEGFR-2
-
Sunitinib (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of receptor tyrosine kinases (RTKs) might be useful tools for monitoring RTKs levels in tumor tissue giving valuable information for anti-angiogenic therapy. Herein we report the synthesis of 5-methoxy-sunitinib 5 and its 11C-radiolabeled analog [11C]-5. The non-radioactive reference compound 5 was prepared by Knoevenagel condensation of 5-methoxy-2-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. A binding constant (Kd) of 20 nM for 5 was determined by competition binding assay against VEGFR-2. In addition, the binding mode of sunitinib and its 5-methoxy substituted derivative was studied by flexible docking simulations. These studies revealed that the substitution of the fluorine at position 5 of the oxindole scaffold by a methoxy group did not affect the inhibitor orientation, but affected the electrostatic and van der Waals interactions of the ligand with residues near the DFG motif of VEGFR-2. 5-[11C]methoxy-sunitinib ([11C]-5) was synthesized by reaction of the desmethyl precursor with [11C]CH3I in the presence of DMF and NaOH in 17 ± 3% decay-corrected radiochemical yield at a specific activity of 162-205 GBq/μmol (EOS). In vivo stability studies of [11C]-5 in rat blood showed that more than 70% of the injected compound was in blood stream, 60 min after administration.
- Caballero, Julio,Mu?oz, Camila,Alzate-Morales, Jans H.,Cunha, Susana,Gano, Lurdes,Bergmann, Ralf,Steinbach, Joerg,Kniess, Torsten
-
p. 272 - 280
(2013/02/23)
-
- Regioselective synthesis of heteroaryl triflones by LDA (lithium diisopropylamide)-mediated anionic thia-Fries rearrangement
-
Novel heteroaryl triflones including oxindole, pyrazolone, pyridine, and quinoline derivatives have been regioselectively synthesized by LDA-mediated thia-Fries rearrangement for the first time. These reactions are also the first examples of the application of anionic thia-Fries rearrangement in heteroaromatic compounds.
- Xu, Xiu-Hua,Wang, Xin,Liu, Guo-Kai,Tokunaga, Etsuko,Shibata, Norio
-
supporting information; experimental part
p. 2544 - 2547
(2012/07/14)
-
- Synthesis of spiro[furan-3,3′-indolin]-2′-ones by PET-catalyzed [3+2] reactions of spiro[indoline-3,2′-oxiran]-2-ones with electron-rich olefins
-
An efficient procedure for the synthesis of spiro[furan-3,3′-indolin] -2-ones and dispiro[cycloalkane-1,2′-furan-3′,3″-indolin]- 2″-ones has been achieved in high yields and stereoselectivity by photoinduced electron transfer-catalyzed [3+2] reactions of substituted spiro[indoline-3,2′-oxiran]-2-ones with olefins. The reactions proceed by ring opening of spiro[indoline-3,2′-oxiran]-2-ones via C β-O bond cleavage and subsequent cycloaddition with olefins by using 2,4,6-triphenylpyrylium tetarfluoroborate (TPT) as a sensitizer.
- Wang, Lihong,Li, Zhanshan,Lu, Lianhong,Zhang, Wei
-
supporting information; experimental part
p. 1483 - 1491
(2012/03/09)
-
- LRRK2 INHIBITORS
-
Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.
- -
-
Page/Page column 129
(2013/02/28)
-
- Novel Hybrid Compounds
-
This invention relates to novel hybrid compounds, of formula 1 wherein R1 to R7, L and Y are as defined herein, wherein Y denotes a histone deacetylase inhibiting moiety (such as a heterocycle, hydroxamic acid or diamine) and L denotes a linker group the invention also relates to processes for preparing them and their use as therapeutic agents and diagnostic agents.
- -
-
Page/Page column 16
(2012/03/26)
-
- CYCLOHEXYL AMIDE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
-
There are described cydohexyl amide derivatives useful as corticotropin releasing factor (CRF) receptor antagonists
- -
-
Page/Page column 86-87
(2016/02/02)
-
- KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
-
The invention is directed to a compound represented by the following structural formula pharmaceutically acceptable salts thereof: (I). Compounds represented by this structural formula are kinase inhibitors and are therefore disclosed herein for the treatment of cancer. Definitions for the variables in the structural formula are provided herein.
- -
-
Page/Page column 27
(2011/10/31)
-
- Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
-
The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers.
- Mologni, Luca,Rostagno, Roberta,Brussolo, Stefania,Knowles, Phillip P.,Kjaer, Svend,Murray-Rust, Judith,Rosso, Enrico,Zambon, Alfonso,Scapozza, Leonardo,McDonald, Neil Q.,Lucchini, Vittorio,Gambacorti-Passerini, Carlo
-
experimental part
p. 1482 - 1496
(2010/04/29)
-
- 3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
-
The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
- -
-
Page/Page column 101-102
(2010/04/06)
-
- Osmium (VII)-catalyzed oxidation of indoles by potassium hexacyanoferrate (III) in alkaline media: A kinetic and mechanistic study
-
THE REACTION of indoles with Os(VIIl) catalyzed hexacyanoferrate (III) in alkaline media to produce the corresponding oxindole has been studied at constant temperature and ionic strength. The reaction followed first order kinetics with respect to [indole], [OH] and [Os(VIII)], fractional order in [Fe(CN)63-]. The effects of added electrolytes, potassium hexacyanoferrate(II), relative permitivity and temperature have also been studied. A mechanism consistent with the kinetic data is proposed. Furthermore, the structural influence of the indoles on the reactivity has been discussed.
- Taha,Abu-Zuhri,EI Hadi,Amer
-
experimental part
p. 1 - 13
(2010/02/28)
-
- Kinetics and mechanism of the oxidation of indoles by alkaline potassium hexacyanoferrate (III)
-
THE REACTION of indoles with hexacyanoferrate(III) in alkaline media to produce the corresponding oxindoie has been studied at constant temperature and ionic strength. The reaction followed first order kinetics with respect to [indole] and [OH-], whereas fractional order with respect to [Fe(CN)63-] was found. The effects of added electrolytes, potassium hexacyanoferrate(Π), relative permitivity and temperature have also been studied. On the basis of experimental observations, a probable reaction mechanism has been proposed.
- Taha,Abu-Zuhrf,El Hadi,Amer
-
experimental part
p. 15 - 27
(2010/03/25)
-
- Indolinone derivatives and their use in treating disease-states such as cancer
-
Indolinone derivatives, such as compounds of the formula (I): wherein A, m, n, R1, R2, R3, R5 and R6 are described herein, are disclosed herein as being useful in treating mammal having disease-states alleviated by the inhibition of PDK-1 activity.
- -
-
Page/Page column 32
(2010/02/11)
-
- Concise syntheses of the cruciferous phytoalexins brassilexin, sinalexin, wasalexins, and analogues: Expanding the scope of the Vilsmeier formylation
-
(Chemical Equation Presented) Efficient syntheses of the phytoalexins brassilexin, sinalexin, and analogues are demonstrated through the application of the Vilsmeier formylation to indoline-2-thiones followed by a new aqueous ammonia workup procedure. Similarly, a very concise two-pot synthesis of the phytoalexins wasalexins using sequential formylation-amination of indolin-2-ones is described. Remarkably, this novel aqueous ammonia workup allows the sequential one-pot formylation-amination, expanding substantially the scope of the Vilsmeier formylation of both indoline-2-thiones and indolin-2-ones. The examination of the formylation-amination reaction and optimization of conditions, as well as the syntheses and antifungal activities of several brassilexin analogues, are reported.
- Pedras, M. Soledade C.,Jha, Mukund
-
p. 1828 - 1834
(2007/10/03)
-
- SPIRO-SUBSTITUTED PYRROLOPYRIMIDINES
-
The invention provides compounds of formula (I) or a pharmaceutically acceptable salt or ester thereof formula (I) wherein the symbols have the meaning as defined in the description. Said compounds are inhibitors of cathepsin K and/or cathepsin S and are useful for the treatment of diseases and medical conditions in which cathepsin K and/or cathepsin S is implicated, e.g. various disorders including neuropathic pain, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis, multiple sclerosis and tumours.
- -
-
-
- 2-CYANOPYRROLOPYRIMIDINES AND PHARMACEUTICAL USES THEREOF
-
The invention relates to pyrrolo pyrimidines of formula (I), wherein Y represents -(CH2)t-O- or -(CH2)r-S-, p is 1 or 2, r is 1, 2 or 3, t is 1, 2 or 3, or Y is -(CH2)j- or -CH=CH-, j is 1 or 2; p is 1 or 2, or Y is -(CH2)f-, f is 1 or 2, p is 1, and the further radicals and symbols have the meaning as defined herein; their preparation, their use as pharmaceuticals, pharmaceutical compositions containing them, the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment of neuropathic pain and to a method for the treatment of such a disease in animals, especially in humans.
- -
-
Page/Page column 45
(2010/02/08)
-
- Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors
-
The present invention is directed to a class indolinone compounds, hexahydro-cyclohepta-pyrrole oxindoles, which are useful as protein kinase inhibitors.
- -
-
Page/Page column 20
(2010/02/08)
-
- Pyrrole substituted 2-indolinone protein kinase inhibitors
-
The present invention relates to novel pyrrole substituted 2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
- -
-
-
- 3-(cycloalkanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors
-
The present invention relates to novel 3-(cycloalkano-heteroarylidenyl)-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.
- -
-
Page column 25
(2010/02/05)
-
- 3-heteroarylidene-2-indolinone protein kinase inhibitors
-
The present invention relates to novel 3-heteroarylidene-2-indolinone compounds and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
- -
-
-
- 3-(cycloalkanoheteroarylidenyl)-2- indolinone protein tyrosine kinase inhibitors
-
The present invention relates to novel 3-(cycloalkanoheteroarylidenyl)-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.
- -
-
-
- Osmium(VIII) Catalyzed Kinetics and Mechanism of Indoles Oxidation with Aryl-N-Haloamines in Alkaline Medium
-
The kinetics of oxidation of the title substrates by sodium N-haloarylsulfonamides (or aryl-N-haloamines), chloramine-T (CAT), bromamine-T (BAT), chloramine-B (CAB), and bromamine-B (BAB), catalyzed by osmium(VIII) in alkaline medium has been studied at 30 deg C.The corresponding oxindoles and arylsulfonamides have been characterized as reaction products. The reaction rate shows a first-order dependence each on 0 and 0, a fractional-order on , and an inverse first-order on ->.Addition of arylsulfonamide, chloride and bromide, and variation of ionic strength of the medium have no effect on the reaction rate.There is a negative effect of dielectric constant of the solvent.Activation parameters have been calculated from the Arrhenius and Eyring plots.Hammet correlation of substituent effects indicates and LFE relationship with ? = -1.0, showing the formation of an electron deficient transition state.From enthalpy-entropy relationships and Exner correlations, the isokinetic temperatures (333 K and 326 K) have been determined for the reactions of CAT and BAT, respectively.Proton inventory studies in H2O-D2O mixtures have shown the involvement of a single exchangeable proton of OH- ion in the transition state.A mechanism consistent with the observed kinetics has been proposed.
- Rangappa, K. S.,Ramachandra, H.,Mahadevappa, D. S.,Gowda, N. M. Made
-
p. 265 - 274
(2007/10/03)
-
- Oxindole alkaloids. A novel non-biomimetic entry to (-)-horsfiline
-
A novel non-biomimetic synthesis of horsfiline has been developed. The key pyrrolidine forming reaction is the 1,3-dipolar cycloaddition of the thermally generated N-methylazomethine ylide to a suitable 3-akylidene-indolin-2(3H)one. The same strategy was also applied to the synthesis of pure (R)-(-)-enantiomer.
- Palmisano, Giovanni,Annunziata, Rita,Papeo, Gianluca,Sisti, Massimo
-
-
- A new efficient and mild synthesis of 2-oxindoles by one-pot Wolff-Kishner like reduction of isatin derivatives
-
Indole-2-one derivatives were prepared from the corresponding isatines via one pot reduction in hydrazine hydrate.
- Crestini,Saladino
-
p. 2835 - 2841
(2007/10/02)
-
- Preparation of indoles and oxindoles from N-(tert-butoxycarbonyl)-2-alkylanilines
-
Treatment of dilithiated N-(tert-butoxycarbonyl)anilines 1 with dimethylformamide or carbon dioxide furnishes intermediates 3, 5, that are easily converted to N-(tert-butoxycarbonyl)indoles 4 and oxindoles (indol-2(3H)-ones, 7), respectively. Condensation of dilithiated 1 with N-methoxy-N-methylamides provides ketones 9 which are cyclized upon trifluoroacetic acid treatment to either 2-substituted 1-(tert-butoxycarbonyl)indoles 10 or 2-substituted indoles 11 depending on the reaction time. This general methodology has been applied to efficient synthesis of 1,2-alkyl-bridged indoles 12, 1,3,4,5-tetrahydrobenz[c,d]indole (16), 2a,3,4,5-tetrahydrobenz[c,d]indol-2(1H)-one (18), and 1-(tert-butoxycarbonyl)1H-pyrrolo[2,3-b]pyridine (21).
- Clark,Muchowski,Fisher,Flippin,Repke,Souchet
-
p. 871 - 878
(2007/10/02)
-
- A NOVEL ELECTROPHILIC N-AMIDATION VIA ELECTRON DEFICIENT COMPLEXES : ACTION OF FERRIC CHLORIDE OF N-ACETYLOXYAMIDES
-
The action of FeCl3 on N-acetyloxyamides leads to electron deficient species which can react intra or intermolecularly with an aromatic group to give oxindoles or analogues.
- Cherest, Marc,Lusinchi, Xavier
-
p. 715 - 718
(2007/10/02)
-
- Electrophilic Aromatic Substitution with N-Methoxy-N-acylnitrenium Ions Generated from N-Chloro-N-methoxyamides: Syntheses of Nitrogen Heterocyclic Compounds Bearing a N-Methoxyamide Group
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N-Methoxy-N-acylnitrenium ions (II), generated by treatment of N-chloro-N-methoxyamides with silver carbonate in trifluoroacetic acid, react with arenes to give N-aryl-N-methoxyamides in good yields.In the case of the intramolecular cyclization of N-chloro-N-methoxy-2-phenylacetamides, the mode of cyclization is highly dependent on the nature of ortho or para substituent groups.Nitrenium ions II can primarily attack three positions (C-1, C-2, and C-6) of a phenyl ring.Normally II attack C-6.On the other hand, when the ortho position was occupied with a substituent group, II attacked both C-2 and C-6, in the former case followed by a 1,2-substituent migration, which was proved by a deuterium labeling experiment.Especially, when a methoxy group is substituted on ortho or para position, II attack C-1 due to the effect of the electron-releasing methoxy group to give spiro dienone compounds 39.A general discussion of the utility and mechanistic details of these reactions is presented.
- Kawase, Masami,Kitamura, Takahiro,Kikugawa, Yasuo
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p. 3394 - 3403
(2007/10/02)
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- A Simple Synthesis of 5-Methoxyindole and 5-Methoxy-2-oxindole
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1-Methoxy- and 1-hydroxy-2-oxindoles rearranged in acidic solution to 5-substituted 2-aminophenylacetic acid derivatives which were cyclized to the corresponding 2-oxindoles with heating.The synthesis of 5-methoxyindole from 5-methoxy-2-oxindole was also described.
- Sakamoto, Takeshi,Hosoda, Isao,Kikugawa, Yasuo
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p. 1279 - 1281
(2007/10/02)
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- 1,3-disubstituted 2-oxindoles as analgesic and anti-inflammatory agents
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Certain 2-oxindole-1-carboxamide compounds having an acyl substituent at the 3-position, and also on the carboxamide nitrogen atom, are inhibitors of the cyclooxygenase (CO) and lipoxygenase (LO) enzymes, and are useful as analgesic agents and anti-inflammatory agents in mammalian subjects. These 2-oxindole-1-carboxamide compounds are of particular value for acute administration for ameliorating pain in human patients recovering from surgery or trauma, and also for chronic administration to human subjects for alleviating the symptoms of chronic diseases, such as rheumatoid arthritis and osteoarthritis. Certain 2-oxindole-1-carboxamide compounds unsubstituted at C-3, but having an acyl substituent on the carboxamide nitrogen atom, are useful as intermediates to the aforementioned analgesic and anti-inflammatory agents.
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- 1,3-dicarboxamide-oxindoles as antiinflammatory agents
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1,3-Dicarboxamidooxindoles as antiinflammatory agents prepared by reaction of the 1-carbamoyloxindole with an isocyanate or by aminolysis of the corresponding alkyl 1-carbamoyloxindole-3-carboxylate.
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