- Hydrophobic derivatization of N-linked glycans for increased ion abundance in electrospray ionization mass spectrometry
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A library of neutral, hydrophobic reagents was synthesized for use as derivatizing agents in order to increase the ion abundance of N-linked glycans in electrospray ionization mass spectrometry (ESI MS). The glycans are derivatized via hydrazone formation and are shown to increase the ion abundance of a glycan standard more than 4-fold. Additionally, the data show that the systematic addition of hydrophobic surface area to the reagent increases the glycan ion abundance, a property that can be further exploited in the analysis of glycans. The results of this study will direct the future synthesis of hydrophobic reagents for glycan analysis using the correlation between hydrophobicity and theoretical non-polar surface area calculation to facilitate the development of an optimum tag for glycan derivatization. The compatibility and advantages of this method are demonstrated by cleaving and derivatizing N-linked glycans from human plasma proteins. The ESI-MS signal for the tagged glycans are shown to be significantly more abundant, and the detection of negatively charged sialylated glycans is enhanced.
- Walker, S. Hunter,Lilley, Laura M.,Enamorado, Monica F.,Comins, Daniel L.,Muddiman, David C.
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Read Online
- 4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors
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In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.
- Gavara, Laurent,Legru, Alice,Verdirosa, Federica,Sevaille, Laurent,Nauton, Lionel,Corsica, Giuseppina,Mercuri, Paola Sandra,Sannio, Filomena,Feller, Georges,Coulon, Rémi,De Luca, Filomena,Cerboni, Giulia,Tanfoni, Silvia,Chelini, Giulia,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
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- TBSOTf-promoted versatile N-formylation using DMF at room temperature
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Hydrazides and amines were N-formylated by DMF in the presence of tert-butyldimethylsilyl triflate (TBSOTf) at room temperature, in good to excellent yields.
- Sakurai, Masayoshi,Kawakami, Rina,Kihara, Nobuhiro
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supporting information
p. 1291 - 1294
(2019/04/10)
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- Synthesis of N′-propylhydrazide analogs of hydroxamic inhibitors of histone deacetylases (HDACs) and evaluation of their impact on activities of HDACs and replication of hepatitis C virus (HCV)
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N′-Propylhydrazide analogs of hydroxamic inhibitors of histone deacetylases (HDACs), including tubastatin A, vorinostat and belinostat, were synthesized. All prepared compounds inhibited HDAC1/2/3, but not HDAC6, except for one hydrazide analog of HDAC4/5/7 inhibitor that was completely inactive. A novel 4-substituted derivative of N′-propylbenzohydrazide with extremely high anti-HCV activity was discovered.
- Kozlov, Maxim V.,Konduktorov, Konstantin A.,Shcherbakova, Anastasia S.,Kochetkov, Sergey N.
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supporting information
p. 2369 - 2374
(2019/06/17)
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- Synthesis and anti-coronavirus activity of a series of 1-thia-4-azaspiro[4.5]decan-3-one derivatives
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A series of 1-thia-4-azaspiro[4.5]decan-3-ones bearing an amide group at C-4 and various substitutions at C-2 and C-8 were synthesized and evaluated against human coronavirus and influenza virus. Compounds 7m, 7n, 8k, 8l, 8m, 8n, and 8p were found to inhibit human coronavirus 229E replication. The most active compound was N-(2-methyl-8-tert-butyl-3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)-3-phenylpropanamide (8n), with an EC50 value of 5.5 μM, comparable to the known coronavirus inhibitor, (Z)-N-[3-[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]-3-oxo-1-phenylprop-1-en-2-yl]benzamide (K22). Compound 8n and structural analogs were devoid of anti-influenza virus activity, although their scaffold is shared with a previously discovered class of H3 hemagglutinin-specific influenza virus fusion inhibitors. These findings point to the 1-thia-4-azaspiro[4.5]decan-3-one scaffold as a versatile chemical structure with high relevance for antiviral drug development.
- Apayd?n, ?a?la Begüm,Cesur, Nesrin,Stevaert, Annelies,Naesens, Lieve,Cesur, Zafer
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- Dithiocarbamate as a valuable scaffold for the inhibition of metallo-β-lactmases
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The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 50 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 μM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.
- Ge, Ying,Xu, Li-Wei,Liu, Ya,Sun, Le-Yun,Gao, Han,Li, Jia-Qi,Yang, Kewu
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- A combinatorial approach for the discovery of drug-like inhibitors of 15-lipoxygenase-1
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Human 15-lipoxygenase-1 (15-LOX-1) is a mammalian lipoxygenase which plays an important regulatory role in several CNS and inflammatory lung diseases. To further explore the role of this enzyme in drug discovery, novel potent inhibitors with favorable phy
- van der Vlag, Ramon,Guo, Hao,Hapko, Uladzislau,Eleftheriadis, Nikolaos,Monjas, Leticia,Dekker, Frank J.,Hirsch, Anna K.H.
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- Design, synthesis and evaluation against Chikungunya virus of novel small-molecule antiviral agents
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Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells. Structure-activity relationships were elucidated for the original scaffolds, and different novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these promising novel structures as antiviral agents against Chikungunya virus.
- Tardugno, Roberta,Giancotti, Gilda,De Burghgraeve, Tine,Delang, Leen,Neyts, Johan,Leyssen, Pieter,Brancale, Andrea,Bassetto, Marcella
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p. 869 - 874
(2018/01/18)
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- Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus
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Chikungunya virus is a re-emerging arbovirus transmitted to humans by Aedes mosquitoes, responsible for an acute febrile illness associated with painful and debilitating arthralgia, which can persist for several months or become chronic. Over the past few years, infection with this virus has spread worldwide with a previously unknown virulence. No specific antiviral treatments nor vaccines are currently available against this important pathogen. Starting from the structure of a class of selective anti-CHIKV agents previously identified in our research group, different modifications to this scaffold were rationally designed, and 69 novel small-molecule derivatives were synthesised and evaluated for their inhibition of Chikungunya virus replication in Vero cells. Further structure-activity relationships associated with this class of antiviral agents were elucidated for the original scaffolds, and novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these new structures as antivirals against Chikungunya virus.
- Giancotti, Gilda,Cancellieri, Michela,Balboni, Andrea,Giustiniano, Mariateresa,Novellino, Ettore,Delang, Leen,Neyts, Johan,Leyssen, Pieter,Brancale, Andrea,Bassetto, Marcella
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supporting information
p. 56 - 68
(2018/03/06)
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- Exploration of diphenylalkyloxadiazoles as novel cardiac myosin activator
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To explore novel cardiac myosin activator, a series of diphenylalkyl substituted 1,3,4-oxadiazoles and 1,2,4-oxadiazoles have been prepared and tested for cardiac myosin ATPase activation in vitro. In all cases, three carbon spacer between the oxadiazole core and one of the phenyl ring was considered crucial. In case of 1,3,4-oxadiazole, zero to two carbon spacer between oxadiazole core and other phenyl ring are favorable. Phenyl ring can be replaced by cyclohexyl moiety. In case of 1,2,4-oxadiazole, zero or one carbon spacer between the oxadiazole and other phenyl ring are favorable. Introduction of hydrogen bonding donor (NH) group at the 2nd position of the 1,3,4-oxadiazole enhances the activity. Substitutions on either of the phenyl rings or change of phenyl ring to other heterocycle are not tolerated for both the oxadiazoles. The prepared oxadiazoles showed selective activation for cardiac muscle over smooth and skeleton muscles.
- Manickam, Manoj,Boggu, Pulla Reddy,Pillaiyar, Thanigaimalai,Sharma, Niti,Jalani, Hitesh B.,Venkateswararao, Eeda,Jung, Sang-Hun
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supporting information
p. 2369 - 2374
(2018/06/25)
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- HISTONE DEACETYLASE INHIBITORS AND USES THEREOF
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Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.
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Page/Page column 22; 25
(2018/04/27)
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- Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds
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The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate specificity with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fluorescence-based kinase assay that has a Z' factor above 0.5. It identified 15 hits (including nitrogen-containing aromatic, flavone, hydrazone, and naphthalene derivatives) with IC50 values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modification and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein–ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified.
- Gong, Grace Qun,Wang, Ke,Dai, Xin-Chuan,Zhou, Yan,Basnet, Rajesh,Chen, Yi,Yang, De-Hua,Lee, Woo-Jeong,Buchanan, Christina Maree,Flanagan, Jack Urquhart,Shepherd, Peter Robin,Chen, Ying,Wang, Ming-Wei
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p. 1902 - 1912
(2018/07/31)
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- A novel serine racemase inhibitor suppresses neuronal over-activation in vivo
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Serine racemase (SRR) is an enzyme that produces D-serine from L-serine. D-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs’ over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states. In the previous study, we performed in silico screening to identify four compounds with inhibitory activities against recombinant SRR. Here, we synthesized 21 derivatives of candidate 1, one of four hit compounds, and performed screening by in vitro evaluations. The derivative 13J showed a significantly lower IC50 value in vitro, and suppressed neuronal over-activation in vivo.
- Mori, Hisashi,Wada, Ryogo,Takahara, Satoyuki,Horino, Yoshikazu,Izumi, Hironori,Ishimoto, Tetsuya,Yoshida, Tomoyuki,Mizuguchi, Mineyuki,Obita, Takayuki,Gouda, Hiroaki,Hirono, Shuichi,Toyooka, Naoki
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p. 3736 - 3745
(2017/06/13)
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- 2,3,4-Trihydroxybenzyl-hydrazide analogues as novel potent coxsackievirus B3 3C protease inhibitors
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Human coxsackievirus B3 (CVB3) 3C protease plays an essential role in the viral replication of CVB3, which is a non-enveloped and positive single-stranded RNA virus belonging to Picornaviridae family, causing acute viral myocarditis mainly in children. During optimization based on SAR studies of benserazide (3), which was reported as a novel anti-CVB3 3Cpro agent from a screening of compound libraries, the 2,3,4-trihydroxybenzyl moiety of 3 was identified as a key pharmacophore for inhibitory activity against CVB3 3Cpro. Further optimization was performed by the introduction of various aryl-alkyl substituted hydrazide moieties instead of the serine moiety of 3. Among the optimized compounds, 11Q, a 4-hydroxyphenylpentanehydrazide derivative, showed the most potent inhibitory activity (IC50 Combining double low line 0.07 μM). Enzyme kinetics studies indicated that 11Q exhibited a mixed inhibitory mechanism of action. The antiviral activity against CVB3 was confirmed using the further derived analogue (14b) with more cell permeable valeryl ester group at the 2,3,4-trihydroxy moiety.
- Kim, Bo-Kyoung,Ko, Hyojin,Jeon, Eun-Seok,Ju, Eun-Seon,Jeong, Lak Shin,Kim, Yong-Chul
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p. 202 - 216
(2016/05/24)
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- Development of Allosteric Hydrazide-Containing Class i Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia
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One of the biggest hurdles yet to be overcome for the continued improvement of histone deacetylase (HDAC) inhibitors is finding alternative motifs equipotent to the classic and ubiquitously used hydroxamic acid. The N-hydroxyl group of this motif is highly subject to sulfation/glucoronidation-based inactivation in humans; compounds containing this motif require much higher dosing in clinic to achieve therapeutic concentrations. With the goal of developing a second generation of HDAC inhibitors lacking this hydroxamate, we designed a series of potent and selective class I HDAC inhibitors using a hydrazide motif. These inhibitors are impervious to glucuronidation and demonstrate allosteric inhibition. In vitro and ex vivo characterization of our lead analogues' efficacy, selectivity, and toxicity profiles demonstrate that they possess low nanomolar activity against models of acute myeloid leukemia (AML) and are at least 100-fold more selective for AML than solid immortalized cells such as HEK293 or human peripheral blood mononuclear cells.
- McClure, Jesse J.,Zhang, Cheng,Inks, Elizabeth S.,Peterson, Yuri K.,Li, Jiaying,James Chou
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p. 9942 - 9959
(2016/11/19)
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- AUTOTAXIN INHIBITORS
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The present invention relates to compounds of formula (I): wherein R1, R2, R3, R4a, R4b, R4C, R4d, L, A, Q, W and HET are each as defined herein. The compounds of the present inv
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-
Paragraph 00384; 00385
(2016/09/22)
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- PRODUCTION METHOD FOR COMPOUND COMPRISING AMINO GROUP AND/OR HYDROXYL GROUP
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Disclosed is a method for producing a compound having an amino group and/or a hydroxyl group from a substrate compound having an atomic group containing CO or CS by eliminating said atomic group. The substrate compound having an atomic group containing CO or CS (for example, an amide, a carbamate, or the like) is allowed to react with a compound expressed by formula (I) below, at a temperature of 120°C or lower, preferably in the presence of an ammonium salt, to eliminate said atomic group containing CO or CS. In formula (I) A may not be present, and in a case where A is present, A represents an alkyl group having 1 to 6 carbon atoms. ????????H2N-A-NH2?????(I)
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Paragraph 0088
(2015/01/18)
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- NITROGEN-CONTAINING HETEROCYCLIC COMPOUND OR SALT THEREOF
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A compound represented by Formula [1] (in the formula, Z1 represents N, CH, or the like; X1 represents NH or the like; R1 represents a heteroaryl group or the like; each of R2, R3, and R4 represents a hydrogen atom, a halogen atom, an alkoxy group, or the like; and R5 represents a heteroaryl group or the like) or salt thereof.
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Paragraph 1115; 1116; 0117
(2015/11/30)
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- TMSCN/DBU-mediated facile redox transformation of α,β- unsaturated aldehydes to carboxylic acid derivatives
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Redox transformation of an α,β-unsaturated aldehyde to a carboxylic acid derivative by means of a combination of TMSCN and DBU was investigated. In addition to the wide use of the carboxylic acid derivatives provided by this reaction, temperature-dependent control of the kinetic or thermodynamic protonation pattern was found to selectively switch the stereochemistry of the acyl group in the product.
- Kaise, Hiromi,Shimokawa, Jun,Fukuyama, Tohru
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supporting information
p. 727 - 729
(2014/03/21)
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- Alkylsulfanyl-1,2,4-triazoles, a New Class of allosteric valosine containing protein inhibitors. Synthesis and structure-activity relationships
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Valosine containing protein (VCP), also known as p97, is a member of AAA ATPase family that is involved in several biological processes and plays a central role in the ubiquitin-mediated degradation of misfolded proteins. VCP is an ubiquitously expressed, highly abundant protein and has been found overexpressed in many tumor types, sometimes associated with poor prognosis. In this respect, VCP has recently received a great deal of attention as a potential new target for cancer therapy. In this paper, the discovery and structure-activity relationships of alkylsulfanyl-1,2,4-triazoles, a new class of potent, allosteric VCP inhibitors, are described. Medicinal chemistry manipulation of compound 1, identified via HTS, led to the discovery of potent and selective inhibitors with submicromolar activity in cells and clear mechanism of action at consistent doses. This represents a first step toward a new class of potential anticancer agents.
- Polucci, Paolo,Magnaghi, Paola,Angiolini, Mauro,Asa, Daniela,Avanzi, Nilla,Badari, Alessandra,Bertrand, Jay,Casale, Elena,Cauteruccio, Silvia,Cirla, Alessandra,Cozzi, Liviana,Galvani, Arturo,Jackson, Peter K.,Liu, Yichin,Magnuson, Steven,Malgesini, Beatrice,Nuvoloni, Stefano,Orrenius, Christian,Sirtori, Federico Riccardi,Riceputi, Laura,Rizzi, Simona,Trucchi, Beatrice,O'Brien, Tom,Isacchi, Antonella,Donati, Daniele,D'Alessio, Roberto
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p. 437 - 450
(2013/04/10)
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- In situ generation of diimide from hydrazine and oxygen: Continuous-flow transfer hydrogenation of olefins
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No catalyst required! A highly efficient, catalyst-free process to generate diimide in situ from hydrazine monohydrate and molecular oxygen for the selective reduction of alkenes has been developed. The use of a gas-liquid segmented flow system allowed safe operating conditions and dramatically enhanced this atom-economical reaction, resulting in short processing times. Copyright
- Pieber, Bartholomaeus,Martinez, Sabrina Teixeira,Cantillo, David,Kappe, C. Oliver
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supporting information
p. 10241 - 10244
(2013/10/21)
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- Synthesis, characterization and evaluation of some 5-substituted 1,3,4-oxadiazole-2-thioesters as antifungal agents
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A series of 5-substituted 1,3,4-oxadiazole-2-thioesters was synthesized by converting several substituted organic acids successively into the corresponding esters, hydrazides and 5-substituted 1,3,4-oxadiazole-2-thiols. Finally the target compounds: 5-substituted 1,3,4-oxadiazole-2-thioesters were obtained by refluxing 5-substituted 1,3,4-oxadiazole-2-thiols in the presence of acid chloride and potassium hydroxide. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.
- Hasan, Aurangzeb,Sheikh, Md Rezaul Karim,Gapil, Shelly
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experimental part
p. 2573 - 2578
(2012/09/07)
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- Design and synthesis of new (E)-cinnamic N-acylhydrazones as potent antitrypanosomal agents
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We report herein the synthesis and trypanocidal profile of new (E)-cinnamic N-acylhydrazones (NAHs) designed by exploiting molecular hybridization between the potent cruzain inhibitors (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl) prop-2-en-1-one and (E)-3-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)-7- methoxy-2-naphthohydrazide. These derivatives were evaluated against both amastigote and trypomastigote forms of Trypanosoma cruzi and lead us to identify two compounds that were approximately two times more active than the reference drug, benznidazole, and with good cytotoxic index. Although designed as cruzain inhibitors, the weak potency displayed by the best cinnamyl NAH derivatives indicated that another mechanism of action was likely responsible for their trypanocide action.
- Carvalho, Samir A.,Feitosa, Larisse O.,Soares, Marcio,Costa, Thadeu E.M.M.,Henriques, Maria G.,Salomao, Kelly,De Castro, Solange L.,Kaiser, Marcel,Brun, Reto,Wardell, James L.,Wardell, Solange M.S.V.,Trossini, Gustavo H.G.,Andricopulo, Adriano D.,Da Silva, Edson F.,Fraga, Carlos A.M.
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p. 512 - 521
(2012/09/07)
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- Synthesis, characterization and antifungal activity of some new 5-substituted 1,3,4-oxadiazole-2-thiols
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A series of 5-substituted 1,3,4-oxadiazol-2-thiols (3a-i) was synthesized by refluxing variably substituted organic acids (Ra-i) with methanol to the corresponding esters (1a-i). These esters were then converted to hydrazides (2a-i) by reaction with hydrazine hydrate in the presence of absolute ethanol which was followed by reaction with carbon disulfide and potassium hydroxide. Structure of the synthesized compounds was established by physicochemical and spectral data analysis. Synthesized compounds were subjected to antifungal activity. Antifungal activity was performed against Aspergillus flavus, Mucor species, Aspergillus niger and Aspergillus fumigates, with test compounds at a concentration of 200 μg/mL. Terbinafine was used as the standard drug.
- Hasan, Aurangzeb,Gapil, Shelly,Khan, Izzat
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experimental part
p. 2007 - 2010
(2012/02/14)
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- Synthesis, characterization and antifungal evaluation of 5-substituted-4-amino-1,2,4-triazole-3-thioesters
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A series of 5-substituted-4-amino-1,2,4-triazole-3-thioesters was synthesized by converting variously substituted organic acids successively into the corresponding esters, hydrazides, 5-substituted-1,3,4-oxadiazole-2-thiols, 5-substituted-1,2,4-triazole-2-thiols and 5-substituted-1,3,4-oxadiazole-2- thioesters. Finally the target compounds were obtained by refluxing 5-substituted-1,3,4-oxadiazole-2-thioesters in the presence of hydrazine hydrate and absolute alcohol. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.
- Hasan, Aurangzeb,Thomas, Noel Francis,Gapil, Shelly
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scheme or table
p. 1297 - 1309
(2011/04/24)
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- Synthesis, characterization and antifungal activity of some 5-substituted 4-amino-1,2,4-triazole-3-thiols
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A series of 5-substituted 4-amino-1,2,4-triazole-3-thiols (4a-i) was synthesized by refluxing substituted organic acids (a-i) with methanol to the corresponding esters (1a-i). These esters were then converted to hydrazides (2a-i) by reaction with hydrazine hydrate in the presence of absolute ethanol. The hydrazides were then converted to 5-substituted 1,3,4-oxadiazole-2-thiols (3a-i) by cyclization reaction with carbon disulfide and KOH which was followed by reaction with hydrazine hydrate in the presence of absolute ethanol. Structure of the synthesized compounds was established by physico-chemical and spectral data analysis. Synthesized compounds were subjected to antifungal activity. Antifungal activity analysis was performed against Aspergillus flavus, Mucor species, Aspergillus niger and Aspergillus fumigates, with test compounds at a concentration of 200 μg/mL. Terbinafine was used as the standard drug.
- Hasan, Aurangzeb,Akhtar, Mohammad Nadeem,Gapil, Shelly
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scheme or table
p. 5471 - 5476
(2012/07/27)
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- NOVEL 1,2,4-TRIAZOLE DERIVATIVES AND PROCESS OF MANUFACTURING THEREOF
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The invention provides 1,2,4-triazole compounds, compositions containing those compounds, methods of treating diseases and/or disorders with those compounds and processes of manufacturing 1,2,4-triazole compounds.
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Page/Page column 29
(2009/10/01)
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- Antimicrobial evaluation of imines and thiazolidinones derived from 3-phenylpropane hydrazide
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Methyl 3-phenylpropanoate (1), after hydrazination into 3-phenylpropanehydrazide (2), was converted into N-arylidene-3-phenylpropane hydrazides (3a-e), which on cyclization with thioglycolic acid yielded N-(4-oxo-2-arylthiazolidin-3-yl)-3-phenylpropanamides (4a-e). All the proposed structures of newly synthesized compounds were in full agreement with the spectral data. Due to para substitution, compound 3a, 4a and 4b were found to be the most potent when evaluated for antibacterial and antifungal activities.
- Fuloria, Neeraj K.,Singh, Vijender,Yar, Mohammad Shahar,Ali, Mohammad
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experimental part
p. 371 - 377
(2010/03/03)
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- Nickel-catalyzed C-H alkenylation and alkylation of 1,3,4-oxadiazoles with alkynes and styrenes
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(Chemical Equation Presented) The addition reaction of 1,3,4-oxadiazoles to alkynes via C-H bond cleavage efficiently proceeds in the presence of a nickel catalyst. This direct coupling allows a facile access to alkenyl-substituted oxadiazoles. The reaction with styrenes in place of alkynes is also available to selectively afford the corresponding branched adducts.
- Mukai, Tomoya,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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supporting information; experimental part
p. 6410 - 6413
(2009/12/06)
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- Efficient approaches to S-alkyl-N-alkylisothioureas: Syntheses of histamine H3 antagonist clobenpropit and its analogues
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(Chemical Equation Presented) S-Alkyl-N-alkylisothioureas were efficiently synthesized via synthetic approach (A) using 3-phenylpro-pionyl isothiocyanate (PPI). The utility of the approach was proved by the syntheses of clobenpropit, a potent histamine H3 antagonist, and its analogues. Alternatively, clobenpropit could be prepared via intramolecular amide cleavage (B) with use of 2-nitrophenylacetyl isothiocyanate (NPAI).
- Yoneyama, Hiroki,Shimoda, Ayako,Araki, Lisa,Hatano, Kouta,Sakamoto, Yasuhiko,Kurihara, Takushi,Yamatodani, Atsushi,Harusawa, Shinya
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p. 2096 - 2104
(2008/09/19)
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- Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1
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A new series of growth hormone secretagogue (GHS) analogues based on the 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and their ability to stimulate intracellular calcium release to the cloned hGHS-1a ghrelin receptor expressed in LLC PK-1 cells. We have synthesized potent ligands of this receptor, some of them behaving as agonists, partial agonists, or antagonists. Some compounds among the most potent, i.e., agonist 29c (JMV2873), partial agonists including 21b (JMV2810), antagonists 19b (JMV2866) and 19c (JMV2844), were evaluated for their in vivo activity on food intake, after sc injection in rodents. Some compounds were found to stimulate food intake like hexarelin; some others were identified as potent hexarelin antagonists in this assay. Among the tested compounds, 21b was identified as an in vitro ghrelin receptor partial agonist, as well as a potent in vivo antagonist of hexarelin-stimulated food intake in rodents. Compound 21b was without effect on GH release from rat. However, in this series of compounds, it was not possible to find a clear correlation between in vitro and in vivo results.
- Demange, Luc,Boeglin, Damien,Moulin, Aline,Mousseaux, Delphine,Ryan, Joanne,Bergé, Gilbert,Gagne, Didier,Heitz, Annie,Perrissoud, Daniel,Locatelli, Vittorio,Torsello, Antonio,Galleyrand, Jean-Claude,Fehrentz, Jean-Alain,Martinez, Jean
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p. 1939 - 1957
(2008/02/02)
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- IMIDAZOPYRIDINE COMPOUND
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The present invention provides an imidazopyridine compound represented by formula (I), wherein R1 and R2 each independently represent a C1-6 alkyl group et al; R3 and R4 each independently represent a hydrogen atom, a methyl et al; Ar1 is a divalent substituent representing a monocyclic or bicyclic, 3- to 8-membered aromatic or aliphatic heterocyclic group et al; Ar2 represents an aromatic carbocyclic group, or an aromatic heterocyclic group; W represents -(CH2)m et al, and m indicates an integer of from 0 to 10. This compound acts as a melanin concentrating hormone receptor antagonist, and is useful as treating agents for obesity.
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Page/Page column 44
(2008/06/13)
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- Reactions of isomeric arylchloropyruvates and glycidates with hydrazines
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Reactions of arylchloropyruvic acids esters with aryl- and hetarylhydrazines give rise to pyrazolinedione hydrazones as a result of a tandem condensation of the substituted hydrazines with arylchloropyruvates. In contrast to this process in reaction with hydrazine hydrate a ready reduction unexpectedly occurs by Kizhner-Wolff mechanism affording 3- hydroxydihydrocinnamic acid hydrazide as the principal product. The isomeric arylglycidate reacts along the same pattern. 2005 Pleiades Publishing, Inc.
- Mamedov,Mustakimova,Gubaidullin,Litvinov,Levin
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p. 694 - 702
(2007/10/03)
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- NAPHTHYRIDINE INTEGRASE INHIBITORS
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The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
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- Intramolecular addition of acyldiazenecarboxylates onto double bonds in the synthesis of heterocycles
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Appropriate aryl-substituted unsymmetrical azodicarbonyl compounds, generated from bishydrazides by oxidation, undergo intramolecular cyclisations to furnish a variety of useful heterocycles such as N-substituted oxindoles, carbostyrils, benzazepinones, benzazocinones, benzimidazolones, benzoxazinones and pyrazolones in varying degrees of efficiency. Methods are described to remove the N-acyl groups from the heteroaromatic compounds. Under mildly acidic conditions where equal opportunities are available for an ipso or a normal cyclisation it is the former process that occurs preferentially. Evidence is presented in favour of a C-to-C migration in the ipso product for the formation of a methoxy-substituted carbostyril derivative. One of the spiro substances is shown to participate in dienone-phenol rearrangement to provide the corresponding quinolone-phenol in high yield.
- Prata, Jose V.,Clemente, Dina-Telma S.,Prabhakar, Sundaresan,Lobo, Ana M.,Mourato, Isabel,Branco, Paula S.
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p. 513 - 528
(2007/10/03)
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- A study on the influence of a silicon group on the Curtius reaction
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The effect of a dimethyl(phenyl)silyl group at different positions with respect to an acyl azide moiety on the Curtius reaction has been investigated. A silyl group at the β-position enhanced the reaction rate by about three times compared to a non-silylated analog. However, a silyl group at the γ-position had only a minor influence on the reaction. A diacyl azide having a silyl group at the β-position with respect to one acyl azide group and at the γ-position with respect to the other acyl azide group has been prepared and subjected to the Curtius reaction in order to evaluate the possible synthetic potential which originates from the control exerted by the silicon group in such systems.
- Verma, Rekha,Ghosh, Sunil K.
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p. 2377 - 2381
(2007/10/03)
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- Carbazoyl derivatives
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A carbazoyl derivative of the general formula: (wherein, R1brepresents a bond, alkylene group of from 1 to 6 carbon atom(s) or alkenylene group of from 2 to 6 carbon atoms,R2brepresents a carbocyclic or heterocyclic ring unsubstituted or substituted by from one to three halogen atom(s), hydroxy group, nitro group, amino group, alkyl or alkoxy group of from 1 to 4 carbon atom(s), 3-aminoureido group, phenoxy group or acylamino group of from 2 to 5 carbon atoms, or R1btogether with R2b, represents an alkyl group of from 1 to 12 carbon atom(s) unsubstituted or substituted by 3-aminoureido group,R3brepresents (1) a hydrogen atom,(2) an alkyl group of from 1 to 6 carbon atom(s) or, (3) a phenyl or benzyl group unsubstituted or substituted by from one to three halogen atom, alkyl or alkoxy group of from 1 to 4 carbon atom(s), hydroxy group or nitro group,Xbrepresents a bond or imino gorup,with the proviso that the compounds wherein the groups shown by Xb-R1b-R2brepresent a phenyl group, 4-aminophenyl gorup, anilino group and 2-thienyl group and the groups shown by R3brepresent a hydrogen atom, are excluded.),or an acid addition salt thereof possesses inhibitory activity on Maillard reaction, and therfore is useful for treating and/or prevention of several diabetic complications and deseases induced by aging.
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