120-23-0Relevant articles and documents
Amino acid derivatives, part 2: Synthesis, antiviral, and antitumor activity of simple protected amino acids functionalized at N-terminus with naphthalene side chain
Ali, Ibrahim A. I.,Al-Masoudi, Iman A.,Saeed, Bahjat,Al-Masoudi, Najim A.,Colla, Palo La
, p. 148 - 155 (2005)
Coupling of various acylated amino acid derivatives with (naphthalen-2-lyloxy)acetic acid (3) in the presence of 1-hydroxy-benzoteriazole (HOBt) and DCC afforded the new amides 6-12. Alternatively, the latter compounds were prepared from reaction of the corresponding hydrazide 5, via the azide-coupling method, with the acylated amino acid derivatives. Treatment of 6, 10-12 with N2H4·H2O afforded the hydrazides 13-16, respectively, as key intermediates for the synthesis of peptide derivatives. Reaction of 12, as a acceptor, with the glycosyl-trichloroimidate 18, as donors in the presence of TMSOTf gave the new glycoside 19. The new compounds were evaluated for their anti-HIV-1, antibovine viral diarrhea virus (BVDV), and antitumor activity.
Synthesis, biological evaluation and molecular modeling study of 3,4-disubstituted 5-mercapto-1,2,4-triazoles
Sahoo, Subhas,Mahendra Kumar,Setty, C. Mallikarjuna
, p. 508 - 512 (2016)
Based on the outcome of computational docking to the active site of cytochrome P450 14α-demethylase (CYP51), diverse 3,4-disubstituted 5-mercapto-1,2,4-triazoles were prepared and screened for antioxidant and antifungal activities. The docking study of synthesized compounds showed promising binding affinity towards docked enzyme, sterol 14α-demethylase(CYP51) from trypanosome cruzi obtained from a RCSB protein data bank (PDB ID: 3KHM). The synthesized compounds were characterized by IR, 1H NMR and Mass spectral data. Among the novel synthesized compounds IV-6, IV-1 and IV-2 showed maximum antifungal activity against A. Niger and C. albicans organism when compared the standard fluconazole. For antioxidant activity, all the compounds showed moderate activity but compound IV-6 and IV-7 showed significant activity when compared to standard ascorbic acid.
Environmentally desirable synthesis without use of organic solvent. Synthesis of aryloxyacetic acids
Villemin, Didier,Hammadi, Mohamed
, p. 4337 - 4341 (1996)
A process using only water as solvent is described for the synthesis of aryloxyacetic acids under microwave irradiation.
Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid analogues
Zhang, Hui,Nakajima, Shotaro,Kato, Hironori,Gu, Liubao,Yoshitomi, Tatsuya,Nagai, Kaoru,Shinmori, Hideyuki,Kokubo, Susumu,Kitamura, Masanori
, p. 822 - 834 (2013)
Background and Purpose 4-Phenylbutyric acid (4-PBA) is a chemical chaperone that eliminates the accumulation of unfolded proteins in the endoplasmic reticulum (ER). However, its chaperoning ability is often weak and unable to attenuate the unfolded protein response (UPR) in vitro or in vivo. To develop more potent chemical chaperones, we synthesized six analogues of 4-PBA and evaluated their pharmacological actions on the UPR. Experimental Approach NRK-52E cells were treated with ER stress inducers (tunicamycin or thapsigargin) in the presence of each of the 4-PBA analogues; the suppressive effects of these analogues on the UPR were assessed using selective indicators for individual UPR pathways. Key Results 2-POAA-OMe, 2-POAA-NO2 and 2-NOAA, but not others, suppressed the induction of ER stress markers GRP78 and CHOP. This suppressive effect was more potent than that of 4-PBA. Of the three major UPR branches, the IRE1 and ATF6 pathways were markedly blocked by these compounds, as indicated by suppression of XBP1 splicing, inhibition of UPRE and ERSE activation, and inhibition of JNK phosphorylation. Unexpectedly, however, these agents did not inhibit phosphorylation of PERK and eIF2α triggered by ER stress. These compounds dose-dependently inhibited the early activation of NF-κB in ER stress-exposed cells. 2-POAA-OMe and 2-POAA-NO2 also inhibited ER stress-induced phosphorylation of Akt. Conclusion and Implications The 4-PBA analogues 2-POAA-OMe, 2-POAA-NO2 and 2-NOAA strongly inhibited activation of the IRE1 and ATF6 pathways and downstream pathogenic targets, including NF-κB and Akt, in ER stress-exposed cells. These compounds may be useful for therapeutic intervention in ER stress-related pathological conditions.
Non-Covalent Synthesis as a New Strategy for Generating Supramolecular Layered Heterostructures
Kumar, Ram,Jalani, Krishnendu,George, Subi J.,Rao
, p. 9751 - 9757 (2017)
Noncovalent synthesis of stable heterostructures (graphene-BN, MoS2-graphene) of layered materials has been accomplished by a ternary host-guest complex as a heterocomplementary supramolecular motif. Besides being reversible, this supramolecular strategy to generate heterostructures may find uses in many situations.
Juvenile hormone mimics with phenyl ether and amide functionality to be insect growth regulators (IGRs): synthesis, characterization, computational and biological study
Awasthi, Pamita,Devi, Vandna
, (2021/10/12)
A series of substituted phenyl ethers derivatives as juvenile hormone (JH) mimics (V1-V8) have been synthesized. Substituted phenoxyacetic acid and amino acid ethyl ester hydrochloride were prepared using NaOH, SOCl2. DCC method has been used for amide linkage. The structure of prepared compounds has been confirmed by Fourier Transform Infra-Red (FT-IR), Electrospray ionization-Mass spectrometry (ESI-MS), Proton and Carbon-13 nuclear magnetic resonance (1H-NMR, 13C-NMR) spectroscopic techniques. Biological efficacy of synthesized analogs has been carried out under laboratory conditions. Galleria mellonella (honey bee pest) has been chosen as testing insect. Juvenile hormone (JH) activity of synthesized compounds has been tested at different concentrations and compared with the standard juvenile hormone analogs (JHAs) pyriproxyfen (M1) and fenoxycarb (M2) against the fifth larval instar of G. mellonella. Compound ethyl 2-[2-(4-methylphenoxy)aminoacetyl]-3-phenyl-propanoate (V6) exhibited better activity among all the synthesized compounds (V1-V8) with LC50 and LC90 values of 0.11 mg/mL and 0.56 mg/mL respectively. Compounds showed insect growth regulating (IGR) activity at lower concentrations. In silico screening of all synthesized compounds with the W-cavity of juvenile hormone-binding protein (JHBP) of insect G. mellonella has been carried out. Chemical reactivity of synthesized series has been studied using DFT/B3LYP/6-311 + G(d,2p) method. Non-toxic behavior of molecules has also been observed from ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) study using discovery studio client 3.0. Communicated by Ramaswamy H. Sarma.
SELECTIVE NON-CYCLIC NUCLEOTIDE ACTIVATORS FOR THE CAMP SENSOR EPAC1
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Paragraph 00168; 00169; 00198; 00242; 00250, (2021/09/26)
The invention relates generally to novel EPAC1 activators, such as Formula (I) and (II) and the preparation thereof as well as the use of EPAC1 activators disclosed herein as to selectively activate EPAC1 in cells.
Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators
Wang, Pingyuan,Luchowska-Stańska, Urszula,Van Basten, Boy,Chen, Haiying,Liu, Zhiqing,Wiejak, Jolanta,Whelan, Padraic,Morgan, David,Lochhead, Emma,Barker, Graeme,Rehmann, Holger,Yarwood, Stephen J.,Zhou, Jia
, p. 5159 - 5184 (2020/06/03)
Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.
Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors
Zhang, Xuandi,Zhang, Guo-Ning,Wang, Yujia,Zhu, Mei,Wang, Juxian,Li, Ziqiang,Li, Donghui,Cen, Shan,Wang, Yucheng
, (2019/02/07)
Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1, D3, D9, G1, G3, G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06–5.77 μm) and low cytotoxicity (CC50 values up to and beyond 100 μm). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.
Microwave (MW), ultrasound (US) and combined synergic MW-US strategies for rapid functionalization of pharmaceutical use phenols
Pawe?czyk, Anna,Sowa-Kasprzak, Katarzyna,Olender, Dorota,Zaprutko, Lucjusz
, (2018/09/26)
Increasingly stringent regulations aimed at protection of the natural environment have stimulated the search for new synthetic methodologies in organic and medicinal chemistry having no or minimum harmful effect. An interesting approach is the use of alternative activation factors, microwaves (MW) or ultrasounds (US) and also their cross-combination, which has been tested in the fast and efficient creation of new structures. At present, an easy and green hybrid strategy (“Lego” chemistry) is generally recommended for the design of new substances from different chemistry building blocks. Often, selected biologically active components with specific chemical reactivities are integrated by a suitably designed homo- or heterodifunctional linker that modifies the functionality of the starting structure, allowing easy covalent linkage to another molecule. In this study, a fast introduction of heterodifunctional halogenoacidic linker to selected mono-, di- and triphenolic active substances, allowing their functionalization, was investigated. Nucleophilic substitution reaction was chosen to produce final ethers with the reactive carboxylic group from phenols. The functionalization was performed using various green factors initiating and supporting the chemical reactions (MW, US, MW-US). The benefits of the three green supporting methods and different conditions of reactions were analyzed and compared with the results of the reaction performed by conventional methods.
