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.
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Bausor
, p. 415 (1939)
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Cooperative binding of magnesium to transfer ribonucleic acid studied by a fluorescent probe
Lynch,Schimmel
, p. 1841 - 1852 (1974)
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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.
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.
