- Exploring Heteroaryl-pyrazole Carboxylic Acids as Human Carbonic Anhydrase XII Inhibitors
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We report the synthesis, biological evaluation, and structural study of a series of substituted heteroaryl-pyrazole carboxylic acid derivatives. These compounds have been developed as inhibitors of specific isoforms of carbonic anhydrase (CA), with potential as prototypes of a new class of chemotherapeutics. Both X-ray crystallography and computational modeling provide insights into the CA inhibition mechanism. Results indicate that this chemotype produces an indirect interference with the zinc ion, thus behaving differently from other related nonclassical inhibitors. Among the tested compounds, 2c with Ki = 0.21 μM toward hCA XII demonstrated significant antiproliferative activity against hypoxic tumor cell lines. Taken together, the results thus provide the basis of structural determinants for the development of novel anticancer agents.
- Cadoni, Roberta,Pala, Nicolino,Lomelino, Carrie,Mahon, Brian P.,McKenna, Robert,Dallocchio, Roberto,Dessì, Alessandro,Carcelli, Mauro,Rogolino, Dominga,Sanna, Vanna,Rassu, Mauro,Iaccarino, Ciro,Vullo, Daniela,Supuran, Claudiu T.,Sechi, Mario
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- Structural modification from agonists to antagonists in the synthesis of new 5-hydroxytryptamine (5-HT3) receptor antagonists and preliminary in-vitro pharmacological evaluation on guinea-pig ileum
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Structural variations from agonists to their selective antagonists follow specific patterns. These patterns in reported molecules or drugs were analysed and common variation patterns, as possible principles to design new antagonistic drugs, were studied.
- Srinivas,Subramanian,Raghavan,Babu, R. Jagadeesh,Gupta,Sridhar,Veeranjaneyulu,Parimoo
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- Exploiting single-molecule magnets of β-diketone dysprosium complexes with C3v symmetry: Suppression of quantum tunneling of magnetization
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A series of four β-diketone mononuclear dysprosium complexes, namely, Dy(EIFD)3(H2O)·CH2Cl2 (1), Dy(EIFD)3(DMF)·CH2Cl2 (2), Dy(EIFD)3(DMSO) (3), and Dy(EIFD)3/su
- Dong, Yanping,Yan, Pengfei,Zou, Xiaoyan,Liu, Tianqi,Li, Guangming
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Read Online
- Cascade Access to Carboline Carboxylates from Indolyl Ketoximes and Acrylates via Palladium-Catalyzed C-H Bond Alkenylation/Annulation
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An efficient palladium-catalyzed C-H bond alkenylation/annulation strategy to access carboline carboxylates from indolyl ketoximes and acrylates through C-C/C-N bond formation is reported. Indolyl ketoximes not only direct ortho -olefination with acrylate
- Fu, Xiao-Pan,Chen, Lu,Wu, Gao-Rong,Liu, Hong-Wei,Xia, Cheng-Cai,Ji, Ya-Fei
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supporting information
p. 69 - 74
(2020/08/24)
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- Rhodium(III)-catalyzed C4-amidation of indole-oximes with dioxazolones: Via C-H activation
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A novel method for the Rh(III)-catalyzed oxime-directed C-H amidation of indoles with dioxazolones has been developed. This strategy provides an exclusive site selectivity and the directing group can be easily removed. This transformation features a wide substrate scope, good functional group tolerance and excellent yields, and may serve as a significant tool to construct structurally diverse indole derivatives for the screening of potential pharmaceuticals in the future. This journal is
- Deng, Ke-Zuan,Fu, Xiao-Pan,Ji, Ya-Fei,Tang, Shi-Biao,Wu, Gao-Rong,Xia, Cheng-Cai,Yang, Jin-Yue,Zhang, Li-Li
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supporting information
p. 7922 - 7931
(2020/11/02)
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- γ-Carboline synthesis enabled by Rh(iii)-catalysed regioselective C-H annulation
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A redox-neutral Rh(iii)-catalyzed C-H annulation of indolyl oximes was developed. Relying on the use of various alkynyl silanes as the terminal alkyne surrogates, the reaction exhibited a reverse regioselectivity, thus giving an exclusive and easy way for the synthesis of a wide range of substituent free γ-carbolines at C3 position with high efficiency. Deuterium-labelling experiments and kinetic analysis have preliminarily shed light on the working mode of this catalytic system. This journal is
- Jiang, Bo,Jia, Jingwen,Sun, Yufei,Wang, Yichun,Zeng, Jing,Bu, Xiubin,Shi, Liangliang,Sun, Xiaoying,Yang, Xiaobo
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supporting information
p. 13389 - 13392
(2020/11/10)
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- Weak Coordination Enabled Switchable C4-Alkenylation and Alkylation of Indoles with Allyl Alcohols
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A weak carbonyl coordination facilitated tunable reactivity between alkenylation and alkylation of indoles at the C4 C-H site is presented using readily accessible allylic alcohols in the presence of Rh catalysis by switching the additives or directing group. Exclusive site selectivity, functional group tolerance, and late-stage modifications are the important practical features.
- Banerjee, Sonbidya,De, Pinaki Bhusan,Mishra, Manmath,Pradhan, Sourav,Punniyamurthy, Tharmalingam
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- Synthesis and bioactivity assessment of novel spiro pyrazole-oxindole congeners exhibiting potent and selective in vitro anticancer effects
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The present work aims to design and synthesize novel series of spiro pyrazole-3,3'-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell li
- Abdelhamid, Sayeda A.,Abo-Salem, Heba M.,Aboul-Soud, Mourad A. M.,Al-Sheikh, Yazeed A.,Ebied, Manal S.,El-Sawy, Eslam R.,Elawady, Mohamed E.,Nassrallah, Amr,Soliman, Ahmed A. F.
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- Synthesis and Inhibitory Effect of Some Indole-Pyrimidine Based Hybrid Heterocycles on α-Glucosidase and α-Amylase as Potential Hypoglycemic Agents
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The Michael addition reaction of barbituric acid with chalcones incorporating the indole scaffold was achieved by using a highly efficient bimetallic Iron–palladium catalyst in the presence of acetylacetone (acac). This catalytic approach produced the desired products in a simple operation and low catalyst loading with acceptable yield of the new hybrids. All tested compounds were subjected for biological activity on α-glucosidase and α-amylase. The results revealed that all synthesized compounds exhibited very good activity against both enzymes when compared to positive control (acarbose). Moreover, compound 5o showed the best activity whereas its IC50 (μM) are 13.02+0.01 and 21.71+0.82 for α-glucosidase and α-amylase respectively. Both compounds 5o and 5l exhibited high similarity in binding mode and pose with amylase protein (4UAC). The obtained data may be used for developing potential hypoglycemic agents.
- Badria, Farid A.,Atef, Saleh,Al-Majid, Abdullah Mohammed,Ali,Elshaier, Yaseen A. M. M.,Ghabbour, Hazem A.,Islam, Mohammad Shahidul,Barakat, Assem
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p. 1288 - 1297
(2019/11/11)
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- Cobalt-Catalyzed Regioselective Direct C-4 Alkenylation of 3-Acetylindole with Michael Acceptors Using a Weakly Coordinating Functional Group
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Herein, we disclosed the first report on the selective C(4)-H functionalization of 3-acetylindole derivatives using first-row transition metal cobalt where an acetyl group is acting as a weakly coordinating directing group. Selective C(4)-H functionalization has been achieved using diverse Michael acceptors (acrylate and maleimide) simply by switching the additive from copper acetate to silver carbonate. Further the formation of a cobaltacycle intermediate was also detected through HRMS for mechanistic insight.
- Banjare, Shyam Kumar,Nanda, Tanmayee,Ravikumar
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supporting information
p. 8138 - 8143
(2019/10/14)
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- Feasible selective synthesis of 3-Acetylindoles and 3-Acetoacetylindoles from β-ethylthio-β-indoly α, β-unsaturated ketones
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An efficient and selective synthesis of 3-acetyl free(N-H)/N-substituded indoles and 3-acetoacetyl free(N-H)/N-substituded indoles has been developed via the hydrolysis reaction of β-ethylthio-β-indoly α, β-unsaturated ketones in the presence of 3 equivalent of NaOH and 5 mol% of H2SO4, respectively. The procedure features easy operation, excellent yields, and high selectivity, compatibility and practicability.
- Wang, Wen-Ju,Yu, Hai-Feng
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p. 377 - 385
(2019/02/07)
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- Novel and simple methodology for the synthesis of 3-acetylindoles and their N-alkyl derivatives using TBAB as phase transfer catalyst
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Using 5% aq. NaOH, a simple method for the transformation of 3-cyanoacetylindoles 2(a-e) into 3-acetylindoles 3 (a-e), in good yields, is reported. Tetrabutylammoniumbromide (TBAB) is found to be an efficient phase transfer catalyst for the synthesis of N-alkyl derivatives 5(a-t) of 3-acetylindoles 3(a-e) giving products in excellent yields. 2 (a-e) were themselves obtained from simple indoles 1 (a-e) by reaction with cyano acetic acid in the presence of propionic anhydride at 100 °C for 5-10 min. Partial hydrolysis of 2 (a-e) under hot acidic conditions yielded the corresponding carboxamides α-(3-indolecarboxoyl)acetamides 4(a-e). Which could be readily transformed into the respective 3(a-e) by refluxing with 5% aq. NaOH for 2-2.5 h.
- Venkatanarayana,Dubey, Pramod K.
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experimental part
p. 656 - 662
(2012/06/01)
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- Formyl-and acetylindols: Vibrational spectroscopy of an expectably pharmacologically active compound family
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In the peresent paper, indole and its seven derivatives were compared, namely 3-formylindole, 1-methyl-3-formylindole, 1-ethyl-3-formylindole, 3-acetylindole, 1-methyl-3-acetylindole, 1-ethyl-3-acetylindole and 1,3-diacetylindole. The substitution of indole in position 3 with aldehydes and with alkyl groups cause only minor changes in the molecular geometry, however, substantially larger alterations are found in the charge distribution and in the vibrational force constants. The appearance of the aldhyde groups increased the degree of association as it was observable on the shape of infrared NH stretching band and its shifts. The alkyl substitution shifts the aldehyde carbonyl stretch band frequencies to somewhat higher values. The effect of the second acetyl group in position 1 is not comparable with those of the 1-alkyl groups. The latter effect is observable in the molecular geometry, however, it is more pronounced in the changes of the net charge distribution, the vibrational force constants and the infrared spectra.
- Billes, Ferenc,Podea, Paula Veronica,Mohammed-Ziegler, Ildikó,To?a, Monica,Mikosch, Hans,Irimie, Dan-Florin
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scheme or table
p. 1031 - 1045
(2012/06/30)
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- Towards the syntheses of N-H and N-alkylated derivatives of meridianins
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(Chemical Equation Presented) Novel N-H and N-alkylated derivatives of meridianins have been synthesized as potential antitumor agents by a two-step conversion of N-tosyl-3-acetylindoles or N-alkyl-3-acetylindoles to the corresponding enaminones using DMF-DMA, with or without added pyrrolidine. Further cyclization with guanidine gave the corresponding 2-aminopyrimidines. The structures of the compounds, thus obtained, were proved by 1H and 13C NMR spectroscopy, NOE experiments and X-ray analysis.
- Simon, Ga?lle,Couthon-Gourves, Hélène,Haelters, Jean-Pierre,Corbel, Bernard,Kervarec, Nelly,Michaud, Fran?ois,Meijer, Laurent
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p. 793 - 801
(2008/03/29)
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- Design and synthesis of novel indole β-diketo acid derivatives as HIV-1 integrase inhibitors
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Diketo acids such as S-1360 (1A) and L-731,988 (2) are potent and selective inhibitors of HIV-1 integrase (IN). A plethora of diketo acid-containing compounds have been claimed in patent literature without disclosing much biological activities and synthetic details (reviewed in Neamati, N. Exp. Opin. Ther. Pat. 2002, 12, 709-724). To establish a coherent structure - activity relationship among the substituted indole nucleus bearing a β-diketo acid moiety, a series of substituted indole-β-diketo acids (4a-f and 5a-e) were synthesized. All compounds tested showed anti-IN activity at low micromolar concentrations with varied selectivity against the strand transfer process. Three compounds, the indole-3-β-diketo acids 5a and 5c, and the parent ester 9c, have shown an antiviral activity in cell-based assays. We further confirmed a keto-enolic structure in the 2,3-position of the diketo acid moiety of a representative compound (4c) using NMR and X-ray crystallographic analysis. Using this structure as a lead for all of our computational studies, we found that the title compounds extensively interact with the essential amino acids on the active site of IN.
- Sechi, Mario,Derudas, Massimiliano,Dallocchio, Roberto,Dessì, Alessandro,Bacchi, Alessia,Sannia, Luciano,Carta, Fabrizio,Palomba, Michele,Ragab, Omar,Chan, Carney,Shoemaker, Robert,Sei, Shizuko,Dayam, Raveendra,Neamati, Nouri
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p. 5298 - 5310
(2007/10/03)
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- Simple N-Alkylation and N-Acylation of 3-Acetylindole and 3-Indolecarbaldehyde
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Using lithium cyanide a simple method for the transformation of 3-acetylindole into the N-alkyl, N-acyl, and N-p-toluenesulfonyl derivatives in good yield is reported. 3-Indolecarbaldehyde is also N-alkylated by the same procedure.
- Kurihara, Takushi,Fujimoto, Toshiro,Harusawa, Shinya,Yoneda, Ryuji
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p. 396 - 397
(2007/10/02)
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