35887-71-9Relevant academic research and scientific papers
Discovery of 4-aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 inhibitors. Part I: Optimization of in vitro potencies and pharmacokinetic properties
Lee, Ying-Shuan E.,Chuang, Shih-Hsien,Huang, Lynn Y. L.,Lai, Chun-Liang,Lin, Yu-Hsiang,Yang, Ju-Ying,Liu, Chia-Wei,Yang, Sheng-Chuan,Lin, Her-Sheng,Chang, Chia-Chi,Lai, Jun-Yu,Jian, Pei-Shiou,Lam, King,Chang, Jia-Ming,Lau, Johnson Y. N.,Huang, Jiann-Jyh
, p. 4098 - 4110 (2014/06/09)
A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4′ 4-methoxyphenoxy and 4-(o-fluoropyridyl) carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 μM·h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [ 3H]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.
IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
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Paragraph 00277, (2013/06/27)
Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents for neoplastic diseases
Modulators Of HEC1 Activity And Methods Therefor
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Page/Page column 12, (2011/10/10)
Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.
Protiodeacylation of 4-Substituted 1-Acetyl-2,6-dimethylbenzenes in Sulphuric Acid: Kinetics and Mechanism
Al-Ka'bi, Ja'far,Farooqi, Jameel A.,Gore, Peter H.,Nassar, Ahmed M. G.,Saad, Esmat F.,at al.
, p. 943 - 950 (2007/10/02)
In 89.8percent (w/w) sulphuric acid rate coefficients (1E4k1/s-1) for the protiodeacetylation of 4-substituted (X) 1-acetyl-2,6-dimethylbenzenes (1) were, at 25 deg C; X=Br, 0.468; I, 0.509; Cl, 0.635; H, 1.345; F, 2.52; Ph, 31.5; t-Bu, 38.6; and Me, 47.2.At 25 deg C the reaction of the ketone (1; X=OMe) was too fast, and at 80 deg C reactions of the ketones (1; X=CONH2 or CO2H) were too slow, for convenient measurement.The carboxy nitrile (X=CN) underwent hydratation to the amide (X=CONH2) rather than protiodeacetylation.The rate coefficients at 25 deg C of eight ketones (1) gave an accurate Hammett correlation, with ?+ constants, giving ρ = -4.64+/-0.05.The reaction of 1-acetyl-2,4,6-trimethylbenzene (1; X=Me) was studied of a range of acidity (73.6-99.9percent sulphuric acid), and a maximum was found near 86.0percent acid.Rates were also measured in D2SO4-D2O.The mechanism is discussed.
