52751-67-4Relevant academic research and scientific papers
Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G
Trefzger, Ozildéia S.,das Neves, Amarith R.,Barbosa, Natália V.,Carvalho, Diego B.,Pereira, Indiara C.,Perdomo, Renata T.,Matos, Maria F. C.,Yoshida, Nidia C.,Kato, Massuo J.,de Albuquerque, Sérgio,Arruda, Carla C. P.,Baroni, Adriano C. M.
, p. 313 - 324 (2018/11/30)
Using bioisosterism as a medicinal chemistry tool, 16 3,5-diaryl-isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3-dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T.?cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L.?amazonensis and L.?braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5?μM against L.?amazonensis and IC50 values of 1.2, 2.1 and 6.4?μM on L.?braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250?μM) than pentamidine (78.9?μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.
Aerobic oxidative synthesis of 3,5-disubstituted isoxazoles directly from α,β-unsaturated ketones
Li, Zheng,Wen, Gong,Fu, Rugang,Yang, Jingya
, p. 643 - 644 (2016/10/22)
Using an efficient aerobic oxidative method, the synthesis of ten 3,5-disubstituted isoxazoles by treatment of α,β-unsaturated ketones with hydroxylamine and NaOH at room temperature has been achieved.
CATALYTIC REACTION
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Paragraph 0033; 0037, (2015/10/05)
A catalytic reaction comprises several steps: providing a catalyst, wherein the catalyst is metal or metal oxide particles and at least have {110} crystal plane; using the catalyst when performing a cycloaddition reaction. By using the catalyst with high
Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation
Tzanetou, Evangelia,Liekens, Sandra,Kasiotis, Konstantinos M.,Melagraki, Georgia,Afantitis, Antreas,Fokialakis, Nikolas,Haroutounian, Serkos A.
, p. 139 - 149 (2014/06/09)
A series of novel isoxazole derivatives were efficiently synthesized through the adaptation/modification of an in situ synthetic procedure for pyrazoles. All novel compounds were tested against four different cell lines to evaluate their antiproliferative activity. Based on the Hela cells results of this study and previous work, a classification model to predict the anti-proliferative activity of isoxazole and pyrazole derivatives was developed. Random Forest modeling was used in view of the development of an accurate and reliable model that was subsequently validated. A virtual screening study was then proposed for the design of novel active derivatives. Compounds 9 and 11 demonstrated significant cytostatic activity; the fused isoxazole derivative 18 and the virtually proposed compound 2v, were proved at least 10 times more potent as compared to compound 9, with IC50 values near and below 1 μM. In conclusion, a new series of isoxazoles was exploited with some of them exhibiting promising cytostatic activities. Further studies on the substitution pattern of the isoxazole core can potentially provide compounds with cytostatic action at the nM scale. In this direction the in silico approach described herein can also be used to screen existing databases to identify derivatives with anticipated activity.
O-iodoxy benzoic acid–mediated synthesis of 3,5-diarylisoxazoles and isoxazole-3-carboxylic acids
Desai, Vidya G.,Naik, Sneha R.,Dhumaskar, Kashinath L.
supporting information, p. 1453 - 1460 (2016/09/23)
A new, convenient, ecofriendly synthesis of 3,5-diarylisoxazoles is reported from a,b-unsaturated ketoximes. Similarly, a novel synthesis of isoxazole carboxylic acids is also reported. Both the methods use efficient, environmentally friendly, and nontoxic iodoxybenzoic acid (IBX) as an oxidative cyclizing reagent. Easy procedure, environmentally benign reaction conditions, and nontoxicity are advantages to the methodology.
Synthesis and evaluation of 4-(substituted styryl/alkenyl)-3,5-bis(4- hydroxyphenyl)-isoxazoles as ligands for the estrogen receptor
Haddad, Terra,Gershman, Rachel,Dilis, Robert,Hanson, Robert N.,Labaree, David,Hochberg, Richard B.
supporting information, p. 5999 - 6003,5 (2020/07/31)
A series of 3,5-bis (4-hydroxyphenyl) isoxazoles bearing a styryl/alkyl vinyl group at the 4-position were prepared and evaluated as ligands for the estrogen receptor-alpha (ERα). The target compounds were prepared using the Suzuki reaction to couple an iodo-isoxazole intermediate with a series of styryl/alkenyl boronic acids, followed by O-demethylation. The products were evaluated for their estrogen receptor-α ligand binding domain (ERα-LBD) binding affinity using a competitive binding assay. The 4-(4-hydroxystyryl) derivative 4 h displays binding properties similar to those of the previously described pyrazole class of ER ligands, indicating that the ERα-LBD tolerates the presence of the added vinyl group at the 4-position of the isoxazole ring.
17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS FOR THE TREATMENT OF HORMONE-RELATED DISEASES
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Page/Page column 20, (2011/04/14)
The invention relates to 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1) inhibitors, the preparation thereof and the use thereof for the treatment and prophylaxis of hormone-related, especially estrogen-related or androgen-related, diseases.
Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases
Bey, Emmanuel,Marchais-Oberwinkler, Sandrine,Kruchten, Patricia,Frotscher, Martin,Werth, Ruth,Oster, Alexander,Alguel, Oztekin,Neugebauer, Alexander,Hartmann, Rolf W.
, p. 6423 - 6435 (2008/12/22)
The 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the reduction of the weakly active estrone (E1) into the most potent estrogen, 17β-estradiol (E2). E2 stimulates the growth of hormone-dependent diseases via activation of the estrogen receptors (ERs). 17β-HSD1 is often over-expressed in breast cancer cells. Thus, it is an attractive target for the treatment of mammary tumours. The combination of a ligand- and a structure-based drug design approach led to the identification of bis(hydroxyphenyl) azoles as potential inhibitors of 17β-HSD1. Different azoles and hydroxy substitution patterns were investigated. The compounds were evaluated for activity and selectivity with regard to 17β-HSD2, ERα and ERβ. The most potent compound is 3-[5-(4-hydroxyphenyl)-1,3-oxazol-2-yl]phenol (18, IC50 = 0.31 μM), showing very good selectivity, high cell permeability and medium CaCo-2 permeability.
A novel and convenient method for the synthesis of 3, 5-diarylisoxazoles
Desai,Tilve
, p. 3017 - 3020 (2007/10/03)
α,β-Unsaturated oximes of chalcones on treatment with 2,3-Dichloro- 5,6-dicyano-1,4-benzoquinone (DDQ) in methanol furnish 3,5-disubstituted isoxazoles in good yield.
