- A facile regioselective construction of spiro epoxy-bridged tetrahydropyranone frameworks
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Investigations on the reactivity profile of the transient five-membered-ring cyclic carbonyl ylides, generated from α-diazo ketones, in the presence of the C=O group of various simple ketones and symmetrical/unsymmetrical 1,2-diones were carried out. The reaction of α-diazo ketones with 1,2-naphthoquinone furnished interesting diastereomeric cycloadducts in which both the C=O groups acted as dipolarophilic sites. The similar reaction in the presence of several isatin derivatives afforded novel spiro dioxa-bridged indole derivatives as a mixture of diastereomers. The single crystal X-ray structure analysis manifestly revealed the mode of cycloaddition and the stereochemistry of two of the diastereomers. A diverse set of novel spiro epoxy-bridged tetrahydropyranone frameworks have been constructed in good yield via the tandem cyclization-cycloaddition of α-diazo ketones with the C=O group as heterodipolarophile in a regioselective manner.
- Muthusamy,Babu, S. Arulananda,Nethaji
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Read Online
- Rongalite-induced transition-metal and hydride-free reductive aldol reaction: a rapid access to 3,3′-disubstituted oxindoles and its mechanistic studies
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A transition-metal and hydride-free reductive aldol reaction has been developed for the synthesis of biologically active 3,3′-disubstituted oxindoles from isatin derivatives using rongalite. In this protocol, rongalite plays a dual role as a hydride-free
- Anugu, Naveenkumar,Golla, Sivaparwathi,Jalagam, Swathi,Kokatla, Hari Prasad
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supporting information
p. 808 - 816
(2022/02/03)
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- Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and in vitro evaluations
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Managing diabetes that is a global life-threatening problem, remains a challenge for the scientific community. The inhibition of α-amylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates is an effective strategy to control postprandial hyperglycemia. Herein, we report the novel and highly potent inhibitors of α-amylase and α-glucosidase, namely isatin-hydrazide conjugates 1a – 1j that are easily accessed in two steps from simple and inexpensive commercially available isatin. The in vitro bio-evaluations of these compounds revealed that conjugates 1a, 1h and 1f are highly potent inhibitors of α-amylase with IC50 values of 19.6, 12.1 and 18.3 μg/ml, respectively as compared to the standard, acarbose (IC50 = 36.2 μg/ml). Similarly, the conjugates 1a, 1b, 1d, 1f and 1i showed significant activity against α-glucosidase with IC50 values of 14.8, 25.6, 13.2, 14.5 and 16.5 μg/ml, respectively as compared to the acarbose (IC50 = 34.5 μg/ml). Notably, the compounds 1a and 1f were found to be highly potent against both α-amylase and α-glucosidase enzymes, demonstrating about two-fold better inhibitory activity than the reference inhibitor. Molecular docking studies were performed to recognize the possible binding modes of the compounds with the active pocket of the enzymes. The results of this study divulge the potential of these compounds as powerful and inexpensive lead molecules for future investigations.
- Abbasi, Inzamam,Nadeem, Humaira,Saeed, Adil,Kharl, Hafiz Aamir Ali,Tahir, Muhammad Nawaz,Naseer, Muhammad Moazzam
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- Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies
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The serine/threonine protein kinases CDK2 and GSK-3β are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3β inhibitors targeting breast cancer (5a–g, 7a–h, and 13a–b). The N1 -unsubstituted oxindole derivatives, series 5, showed moderate to potent activity on both MCF-7 and T-47D breast cancer cell lines. Compounds 5d–f showed the most potent cytotoxic activity with IC50 of 3.41, 3.45 and 2.27 μM, respectively, on MCF-7 and of 3.82, 4.53 and 7.80 μM, respectively, on T-47D cell lines, in comparison to the used reference standard (staurosporine) IC50 of 4.81 and 4.34 μM, respectively. On the other hand, the N1 -substituted oxindole derivatives, series 7 and 13, showed moderate to weak cytotoxic activity on both breast cancer cell lines. CDK2 and GSK-3β enzyme inhibition assay of series 5 revealed that compounds 5d and 5f are showing potent dual CDK2/GSK-3β inhibitory activity with IC50 of 37.77 and 52.75 nM, respectively, on CDK2 and 32.09 and 40.13 nM, respectively, on GSK-3β. The most potent compounds 5d–f caused cell cycle arrest in the G2/M phase in MCF-7 cells inducing cell apoptosis because of the CDK2/GSK-3β inhibition. Molecular docking studies showed that the newly synthesised N1 -unsubstituted oxindole hybrids have comparable binding patterns in both CDK2 and GSK-3β. The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3β. Whereas, in series 7 and 13, the N1 -substitutions on the oxindole nucleus hinder the compounds from achieving these key interactions with hinge region amino acids what rationalises their moderate to low anti-proliferative activity.
- Eldehna, Wagdy M.,Al-Rashood, Sara T.,Al-Warhi, Tarfah,Eskandrani, Razan O.,Alharbi, Amal,El Kerdawy, Ahmed M.
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p. 270 - 285
(2020/12/18)
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- Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria
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Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 μg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 μg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 μg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.
- Elsayed, Zainab M.,Eldehna, Wagdy M.,Abdel-Aziz, Marwa M.,El Hassab, Mahmoud A.,Elkaeed, Eslam B.,Al-Warhi, Tarfah,Abdel-Aziz, Hatem A.,Abou-Seri, Sahar M.,Mohammed, Eman R.
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p. 384 - 393
(2021/01/13)
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- Development of Novel Oxotriazinoindole Inhibitors of Aldose Reductase: Isosteric Sulfur/Oxygen Replacement in the Thioxotriazinoindole Cemtirestat Markedly Improved Inhibition Selectivity
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Inhibition of aldose reductase (AR), the first enzyme of the polyol pathway, is a promising approach in treatment of diabetic complications. We proceeded with optimization of the thioxotriazinoindole scaffold of the novel AR inhibitor cemtirestat by repla
- Hlavá?, Matú?,Ková?iková, Lucia,Prnová, Marta ?oltésová,?ramel, Peter,Addová, Gabriela,Májeková, Magdaléna,Hanquet, Gilles,Bohá?, Andrej,?tefek, Milan
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supporting information
p. 369 - 381
(2020/01/31)
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- Synthesis, biological evaluation and in silico studies of certain oxindole–indole conjugates as anticancer CDK inhibitors
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On account of their overexpression in a wide range of human malignancies, cyclin-dependent kinases (CDKs) are among the most validated cancer targets, and their inhibition has been featured as a valuable strategy for anticancer drug discovery. In this study, a hybrid pharmacophore approach was adopted to develop two series of oxindole–indole conjugates (6a–i and 9a–f) and carbocycle–indole conjugates (11a,b) as efficient antitumor agents with potential inhibitory action toward CDK4. All oxindole–indole conjugates, except 6i, 9b, and 9c efficiently affected the growth of the human breast cancer MCF-7 (IC50: 0.39 ± 0.05–21.40 ± 1.58 μM) and/or MDA-MB-231 (IC50: 1.03 ± 0.04–22.54 ± 1.67 μM) cell lines, whereas bioisosteric replacement of the oxindole nucleus with indane or tetralin rings (compounds 11a,b) diminished the anti-proliferative activity. In addition, hybrids 6e and 6f displayed effective cell cycle disturbance and proapoptotic capabilities in MCF-7 cells. Furthermore, the efficient anti-proliferative agents towards MCF-7 and/or MDA-MB-231 cell lines (6a–h, 9a, and 9e) were investigated for their potential inhibitory action toward CDK4. Hybrids 6a and 6e displayed good CDK4 inhibitory activity with IC50s equal 1.82 and 1.26 μM, respectively. The molecular docking study revealed that oxindole moiety is implicated in two H-bonding interactions via both (NH) and (C=O) groups with the key amino acids Glu94 and Val96, respectively, whereas the indole framework is stably accommodated in a hydrophobic sub-pocket establishing hydrophobic interactions with the amino acid residues of Ile12, Val20, and Gln98 lining this sub-pocket. Collectively, these results highlighted hybrids 6a and 6e as good leads for further optimization as promising antitumor drugs toward breast malignancy and CDK inhibitors.
- Abdel-Aziz, Hatem A.,Al-Ansary, Ghada H.,Al-Warhi, Tarfah,Aljaeed, Nada,Ayyad, Rezk R.,El Kerdawy, Ahmed M.,Eldehna, Wagdy M.,Ismael, Omnia E.
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- 3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights
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Herein we describe the design and synthesis of two series of sulfonamides featuring N-unsubstituted (4a-c) or N-substituted (7a-o) isatin moieties (as tails) connected to benzenesulfonamide moiety via a hydrazine linker. All the prepared sulfonamides (4a-c and 7a-o) showed potent inhibitory activities toward transmembrane tumor-associated human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, IX and XII with KI range (8.3–65.4 nM) and (11.9–72.9 nM), respectively. Furthermore, six sulfonamides (7e, 7i, 7j, 7m, 7n and 7o) were assessed for their anti-proliferative activity, according to US-NCI protocol, toward a panel of sixty cancer cell lines. Compounds 7j and 7n were the most promising counterparts in this assay displaying broad spectrum anti-proliferative activity toward diverse cell lines. Also, sulfonamide 7n significantly inhibited clonogenicity of HCT-116 cells in a concentration dependent manner in the colony forming assay. Moreover, molecular modeling studies were performed to gain insights for the plausible binding interactions and affinities for the target isatin-based sulfonamides (4a-c and 7a-o) within hCA isoforms II and IX active sites.
- Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,Nocentini, Alessio,Bonardi, Alessandro,Bua, Silvia,Ibrahim, Hany S.,Elaasser, Mahmoud M.,Kry?tof, Vladimír,Jorda, Radek,Gratteri, Paola,Abou-Seri, Sahar M.,Supuran, Claudiu T.
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- Novel hydrazido benzenesulfonamides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies
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As a part of our ongoing efforts towards developing novel carbonic anhydrase inhibitors based on the isatin moiety, herein we report the synthesis and biological evaluation of novel sulfonamides (5a-h, 10a-g and 11a-c) incorporating substituted 2-indolinone moiety (as tail) linked to benzenesulfonamide (as zinc anchoring moiety) through a hydrazide linker. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 671.8: 3549.5 nM, hCA II in the range of 36.8: 892.4 nM; hCA IX in the range of 8.9: 264.5 nM, whereas hCA XII in the range of 9.0: 78.1 nM. In particular, compound 10b emerged as a single-digit nanomolar hCA IX and XII inhibitor (8.9 and 9.2 nM, respectively). Molecular docking studies carried out for compound 10b within the hCA II, IX and XII active sites allowed us to rationalize the obtained inhibition results.
- Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,Nocentini, Alessio,Ibrahim, Hany S.,Bua, Silvia,Abou-Seri, Sahar M.,Supuran, Claudiu T.
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- Polyfunctional 4-quinolinones. Synthesis of 2-substituted 3-hydroxy-4-oxo-1,4-dihydroquinolines
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We present here two new methods based on rearrangement reactions to obtain novel 2-substituted 3-hydroxy-4-oxo-1,4-dihydroquinolines, an important family of heterocycles with potential applications. Alkyl 3-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxylates were obtained by alkoxide promoted rearrangement of alkyl isatinacetates. A second synthetic route involves the alkoxide promoted reaction of both isatin and N-methylisatin, with alkylating agents having acidic methylenes. This reaction leads to the formation of spiroepoxyoxindoles via Darzens' condensation. When phenacyl bromides are used, the initially obtained benzoyl substituted spiroepoxyoxindoles were smoothly transformed into the corresponding 2-benzoyl-3-hydroxy-4-quinolinones with good to excellent yields.
- Shmidt, María S.,Perillo, Isabel A.,Camelli, Alicia,Fernández, María A.,Blanco, María M.
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p. 1022 - 1026
(2016/02/18)
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- Multicomponent synthesis of novel class of isatin and 5-isatinyli-denerhodanine based diaminofuran derivatives
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A simple and efficient method has been developed for the synthesis of a new collection of isatin and 5-isatinylidenerhodanine derivatives carrying furan group, from N-(carboxymethyl)isatin through a multi-component reaction is explained. The reactive 1:1
- Baharfar, Robabeh,Rassi, Somayeh
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p. 393 - 399
(2016/10/18)
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- Iodine-Mediated C-H Functionalization of sp, sp2, and sp3 Carbon: A Unified Multisubstrate Domino Approach for Isatin Synthesis
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(Chemical Equation Presented) Molecular iodine-promoted efficient construction of isatins from 2′-aminophenylacetylenes, 2′-aminostyrenes, and 2′-amino-β-ketoesters is developed via oxidative amidation of sp, sp2, and sp3 C-H bonds. The reaction involves consecutive iodination, Kornblum oxidation, and intramolecular amidation in a single reactor. The present method meets all of the atom and redox economy principles.
- Satish, Gandhesiri,Polu, Ashok,Ramar, Thangeswaran,Ilangovan, Andivelu
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p. 5167 - 5175
(2015/05/27)
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- Eco-friendly chemoselective N-functionalization of isatins mediated by supported KF in 2-MeTHF
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A sustainable, efficient method for the chemoselective N-functionalization of isatins based on the use of KF-Celite in 2-methyltetrahydrofuran is reported. Notably, the protocol allows reactions with a wide range of electrophiles such as alkyl halides, is
- Mamuye, Ashenafi Damtew,Monticelli, Serena,Castoldi, Laura,Holzer, Wolfgang,Pace, Vittorio
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supporting information
p. 4194 - 4197
(2015/08/11)
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- Direct amidation of 2'-aminoacetophenones using I2-TBHP: A unimolecular domino approach toward isatin and iodoisatin
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Synthesis of isatin and iodoisatin from 2'-aminoacetophenone was achieved via oxidative amido cyclization of the sp3 C-H bond using I 2-TBHP as the catalytic system. The reaction proceeds through sequential iodination, Kornblum oxidation, and amidation in one pot. This method is simple, atom economic, and works under metal- and base-free conditions.
- Ilangovan, Andivelu,Satish, Gandhesiri
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p. 4984 - 4991
(2014/06/23)
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- Expedited microwave-assisted N-alkylation of isatins utilizing DBU
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The N-alkylation of a variety of isatins with alkyl or benzylic halides can be effected under microwave irradiation in ethanol using 1,8-diazabicyclo[5.4. 0]undec-7-ene (DBU) as a base. The conditions employed allow for the expedited synthesis of such substrates wherein the products precipitate from the reaction mixture in high yields and high purity after simple filtration. As will be described, microwave irradiation provides a relatively rapid means of effecting N-alkylations of isatin with a variety of benzylic halides, propargyl bromide and ethyl bromoacetate in times ranging from 10-25 min at 140 oC in closed vials. This report involves the first reported use of DBU for this purpose, and in contrast to other methods, allows for the facilitated isolation of pure products while avoiding extractive or chromatographic purification steps. ARKAT-USA, Inc.
- Jordan, Carly A.,Wieczerzak, Krystyna B.,Knisley, Kyle J.,Ketcha, Daniel M.
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p. 183 - 192
(2014/05/20)
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- Synthesis of new 1,3,4-benzotriazepin-5-one derivatives and their biological evaluation as antitumor agents
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New derivatives of 1,3,4-benzotriazepin-5-one were designed and synthesized as structural analogues to the antitumor agents devazepide and asperlicin. An efficient and novel approach to the synthesis of 2-amino-1,3,4-benzotriazepin-5- one 2 was developed and its structure was confirmed. The newly synthesized derivatives were evaluated for their in vitro antitumor activity on 60 different cell lines. Compounds 8 and 9 displayed the most potent antitumor activity against several cell lines specifically ovarian cancer, renal cancer and prostate cancer, while compounds 5, 10 and 12 showed significant activities against UO-31 renal cancer cell line.
- Taher, Azza T.,Mohammed, Lamia W.
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p. 684 - 693
(2013/07/11)
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- Synthesis, complexation and biological activity of new Isatin Schiff-bases
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Some new Schiff-bases derived from condensation of 3-hydrazono-2-oxo-2,3- dihydroindol-1-yl)-acetic acid hydrazide (3) with benzaldehyde, p-methoxy-benzaldehyde and p-chlorobenzaldehyde have been synthesized in high yields via refluxing in EtOH in the pre
- Sallam,Ibrahim,Anwar
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p. 1482 - 1491
(2013/07/25)
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- N-alkylation of isatins utilizing KF/alumina
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The N-alkylation of isatins by a variety of alkyl halides and one acrylate has been demonstrated utilizing KF/Al2O3 in acetonitrile (ACN) under microwave-irradiation (180 °C) or thermally at reflux. ARKAT-USA, Inc.
- Clay, Charles M.,Abdallah, Hagar M.,Jordan, Carly,Knisley, Kyle,Ketcha, Daniel M.
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experimental part
p. 317 - 325
(2012/06/18)
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- USE OF SPIRO-OXINDOLE COMPOUNDS AS THERAPEUTIC AGENTS
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This invention is directed to methods of using spiro-oxindole compounds of formula (I): wherein k, j, Q, R1, R2a, R2b, R2c, R2d, R3a, R3b, R3c, and R3d are as defined herein, as a stereoisomer, enantiomer, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof, for the treatment and/or prevention of hypercholesterolemia, benign prostatic hyperplasia, pruritis and cancer.
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- Activation of the NC-H bond of Morita-Baylis-Hillman adducts of N-substituted isatins with cerium ammonium nitrate (CAN) and alcohol (ROH)
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A study on the activation of the NC-H bond of Morita-Baylis-Hillman adducts of N-substituted isatin with cerium ammonium nitrate (CAN) and saturated and unsaturated alcohols have been carried out. The choice of a Morita-Baylis- Hillman adduct for this stu
- Shanmugam, Ponnusamy,Vaithiyanathan, Vadivel
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experimental part
p. 591 - 599
(2009/10/17)
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- Discovery of novel non-peptide inhibitors of BACE-1 using virtual high-throughput screening
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A novel series of isatin-based inhibitors of β-secretase (BACE-1) have been identified using a virtual high-throughput screening approach. Structure-activity relationship studies revealed structural features important for inhibition. Docking studies suggest these inhibitors may bind within the BACE-1 active site through H-bonding interactions involving the catalytic aspartate residues.
- Yi Mok,Chadwick, James,Kellett, Katherine A.B.,Hooper, Nigel M.,Johnson, A. Peter,Fishwick, Colin W.G.
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scheme or table
p. 6770 - 6774
(2010/06/12)
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- Simple and efficient microwave assisted N-alkylation of isatin
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We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs 2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating.
- Shmidt, Maria Sol,Reverdito, Ana Maria,Kremenchuzky, Lautaro,Perillo, Isabel Amalia,Blanco, Maria Mercedes
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p. 831 - 840
(2008/09/18)
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- Synthesis of the dibenzopyrrocoline alkaloid skeleton: indolo[2,1-a]isoquinolines and related analogues
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The indolo[2,1-a]isoquinoline and pyrrolo[2,1-a]isoquinoline nuclei have been synthesized from N-benzylindole or ethyl 1H-indol-1-ylacetate and N-benzylpyrrole precursors, respectively. Firstly, at C-2 of either the indole or pyrrole nucleus, aromatic rin
- L?tter, Angelique N.C.,Pathak, Rakhi,Sello, Thato S.,Fernandes, Manuel A.,van?Otterlo, Willem A.L.,de Koning, Charles B.
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p. 2263 - 2274
(2007/10/03)
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- OXINDOLE COMPOUNDS AND THEIR USES AS THERAPEUTIC AGENTS
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This invention is directed to oxindole compounds that are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. Pharmaceutical compositions comprising the compounds and methods of using the compounds are also disclosed.
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Page/Page column 75
(2010/11/24)
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- Microwave irradiation for enhancing the regioselective synthesis of 6H-indolo[2,3-b]quinoxalines
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Microwave irradiation (MWI) promotes the regioselective synthesis of 6H-indolo[2,3-b]quinoxaline (5) by condensation of isatin (1) with o-phenylenediamine. Ethyl indolo[2,3-b]quinoxaline-6-acetate (8) was prepared via the carbethoxymethylation of 5, or fr
- El Ashry, El Sayed H.,Ramadan, El Sayed,Hamid, Hamida Abdel,Hagar, Mohamed
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p. 229 - 232
(2007/10/03)
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- Synthesis of isatin and 5-bromoisatin derivatives
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New N-derivatives of isatin were synthesized by treating ethyl chloroacetate, N-(2-chloroethyl)-morpholine, and 1,4-di(chloromethyl)benzene with isatin sodium salt. N-Derivatives of isatin and 5-bromoisatin were also prepared by Mannich reaction.
- Mesropyan,Ambartsumyan,Avetisyan,Sarkisyan,Amazaspyan
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p. 1476 - 1477
(2007/10/03)
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- A NOVEL ALDOSE REDUCTASE ENZYME INHIBITOR, SPIROHYDANTOINYLISATIN-1-ACETIC ACID DERIVATIVE
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A new aldose reductase enzyme inhibitor, spirohydantoinylisatin-1-acetic acid, is synthesized and characterized by its spectroscopic properties.
- Bueyuekbingoel, Erdem,Klopman, Gilles
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p. 889 - 892
(2007/10/03)
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- Isatine derivatives, and their method of use
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A method of treatment of central nervous system disorders with compounds having the formula STR1 and isomers thereof wherein R 1, R 2, R 4, R 5, R 6, and R 7 and as defined in the specification; as well as pharmaceutical compositions thereof.
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- Isatine derivatives, their preparation and use
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A method of treatment with compounds having the formula STR1 R 1 is hydrogen, C 1-6 -alkyl which may be branched, C 3-7 -cycloalkyl, benzyl, phenyl which may be substituted, acyl, hydroxy, C 1-6 -alkoxy, CH 2 CO 2 R'' wherein R'' is hydrogen or C 1-6 -alkyl which may be branched, CH 2 CN, CH 2 CONR IV R V wherein R IV and R V independently are hydrogen or C 1-6 -alkyl, or CH 2 C( NOH)NH 2 ; R 2 is hydrogen, benzyl, C 1-6 -alkyl which may be branched, or C 3-7 -cycloalkyl; R 4, R 5, R 6, R 7 independently are hydrogen, C 1-6 -alkyl which may be branched, phenyl, halogen, C 1-6 -alkoxy, NO 2, CN, CF 3, OCF 3, or SO 2 NR""R''"" wherein R"" and R''"" independently are hydrogen, aralkoxy, aralkyl, or C 1-6 -alkyl; or R 6 and R 7 together form an additional 4 to 7 membered ring which may be aromatic or partial saturated and which may be substituted with halogen, NO 2, CF 3, CN, OCF 3, SO 2 NR"" R""'' wherein R"" and R""'' independently are hydrogen, aralkoxy, aralkyl, or C 1-6 -alkyl, and R 4 and R 5 have the meanings set forth above, are disclosed, as well as pharmaceutical compositions thereof. Certain of the compounds are novel.The compounds and pharmaceutical compositions containing the compounds are useful in the treatment of central nervous system disorders and especially conditions sensitive to excitatory amino acids.
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- 5-fluoroanthranilic fungicides
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Compounds of formula I STR1 where A is OH, B is H, C1-4 alkyl optionally substituted by C1-4 alkoxy carbonyl, C2-4 alkenyl, CONR2 or COR4 R1 is H, R2 is C1-4 alkyl, and R4 is C1-4 alkyl, or phenyl, optionally substituted by carboxy have pesticidal and especially fungicidal activity. Many of the compounds are novel and these compounds per se, form part of the invention.
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- Hydrazone derivatives and their use
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A method of antagonizing the biological effects of an excitatory amino acid of a subject in need of such antagonization, comprising the step of administering to said subject an effective excitatory amino acid antagonizing amount of an indole-2,3-dione-3-h
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- SIMPLE METHOD FOR THE PREPARATION OF 1-SUBSTITUTED ISATINS
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The use of potassium carbonate in dimethylformamide (DMF) makes it possible to carry out the N-alkylation of isatins with alkyl bromides and iodides and acyl chlorides at room temperature and with alkyl chlorides at elevated temperatures (70-80 deg C) without ring opening.The previously inaccesible N-(2-chloroethyl)isatins were obtained by alkylation of isatin with 1,2-dichloroethane.The condensation of isatins with 1,3-dichloro-2-butene takes place only at the chlorine atom in allyl position of the latter.
- Radul, O. M.,Zhungietu, G. I.,Rekhter, M. A.,Bukhanyuk, S. M.
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p. 286 - 288
(2007/10/02)
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