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Chemical Compound Review:

CHEMBL341103 2-[4-[(2S)-2-acetamido-2-[4- (3-hydroxy-2...

Synonyms: CHEBI:311515, KB-75314, AC1L9LQ8, 1qxk, 918657-87-1

Malleron, J.L. et al., Xin, Z. et al., Chattopadhaya, R. et al., Yu, D. et al., Camps, P. et al., et al.

Sha, Huang, Zhan, Okada, Nakagawa, Iwashita, Takegawa, Fujii, Koizumi, Xin, Liu, Abad-Zapatero, Pei, Szczepankiewicz, Li, Zhang, Hutchins, Hajduk, Ballaron, Stashko, Lubben, Trevillyan, Jirousek, van Vliet, Rodenhuis, Wikström, Pugsley, Serpa, Meltzer, Heffner, Wise, Lajiness, Huff, Svensson, Haenen, Bast, Khanapure, Augustyniak, Earl, Garvey, Letts, Martino, Murty, Schwalb, Shumway, Trocha, Young, Zemtseva, Janero, Kuo, Deangelis, Emanuel, Wang, Zhang, Connolly, Chen, Gruninger, Rugg, Fuentes-Pesquera, Middleton, Jolliffe, Murray, Murugesan, Gu, Stein, Bisaha, Spergel, Girotra, Lee, Lloyd, Misra, Schmidt, Mathur, Stratton, Kelly, Bird, Waldron, Liu, Zhang, Lee, Serafino, Abboa-Offei, Mathers, Giancarli, Seymour, Webb, Hunt, Schlapbach, Heng, Di Padova, Camps, Muñoz, Vázquez, Willoughby, Bull, Garcia-Calvo, Jiang, Chapman, Thornberry,

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Disease relevance of Compound 20

Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 microM against NL4-3, 0.021 microM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 microM against FHR-2 (an HIV strain resistant to 8) [1].

High impact information on Compound 20

Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production [2].
Compound 20 also displayed high potency at GSK-3beta [3].
Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats [4].
Regarding selectivity toward the steroidogenic enzymes, compound 16 was relatively selective toward P450 arom, whereas compound 20 was relatively selective toward P450 17 [5].
The binding IC50 of the most potent compound 20 was 22 nM [6].

Biological context of Compound 20

Compound 20 has a Ki of 1.06 X 10(-7) and either competitive or noncompetitive enzyme kinetics depending on what substrate is used in the converting enzyme assay [7].
Compound 20 also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg [8].
Preferential acetylation of the secondary alcoholic function of 19 afforded compound 20 [9].
The best candidate, compound 20, which has a 16-carbon side chain, was evaluated for reduction of the intraocular pressure in genetically glaucomatous Beagles [10].
Compound 20 has a K(i) of 7 nM against human granzyme B and blocks CTL mediated apoptosis with an IC(50) of 3 micromolar [11].

Anatomical context of Compound 20

Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines [12].

Associations of Compound 20 with other chemical compounds

A (2-hydroxy-phenoxy) acetic acid-based phosphotyrosyl mimetic has been linked with an optimized second arylphosphate binding site ligand to produce compound 20 with low micromolar potency against PTP1B, good selectivity over TCPTP (20-fold) and high cell permeability in the Caco-2 system [13].
Oximes 15, 16 and compound 20 with a higher degree of oxidation in ring A have been found active in a 60 cell line antitumor prescreen by virtue of their cytotoxic effect against one or more tumor cell line and were further referred for in vivo hollow fiber bioassay [14].

Gene context of Compound 20

Among the standard compounds tested, L 652,243 was the most active compound in this test with an ED50 value of 0.01 mg/ear and 1 mg/kg po, but unlike this compound, 20 is a selective inhibitor of 5-LO (IC50 = 2 microM) without any significant activity against CO (IC50 greater than 50 microM) [15].
Optimization of this compound class led to compound 20, which inhibits p38alpha in vitro with IC(50)=14 nM and is active in the mouse TNFalpha-release model [16].
Compound 20 did not show any agonist activity but was able to inhibit gastrin-induced acid secretion, with lower potency (ED50 = 15 mg/kg) [17].
DFT calculations [B3LYP/6-31G(d)] on compound 20 gave important parameters of this pyramidalized alkene, such as the pyramidalization angle (61.7 degrees), the strain energy (72.9 kcal/mol), and the HOMO/LUMO gap (3.79 eV) [18].
Furthermore, TZS-8478 (10 mg/kg per day, p.o., for 5 days) had no stimulative effect on uterine growth in ovariectomized rats, and its desulfamoylated compound (20) was little bound to the human estrogen receptor alpha [19].

Analytical, diagnostic and therapeutic context of Compound 20

Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists) [20].

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