The [4]annulene (cyclobutadiene) system. The tetrakis(trifluoromethyl) derivative

1977 ◽  
Vol 99 (10) ◽  
pp. 3524-3526 ◽  
Author(s):  
Satoru Masamune ◽  
Takahisa Machiguchi ◽  
Matsuhiko Aratani
Keyword(s):  
Trifluoromethyl Derivative

ADMET properties of novel 5-O-benzoylpinostrobin derivatives

2019 ◽  
Vol 30 (6) ◽  
Author(s):  
Mohammad Rizki Fadhil Pratama ◽  
Hadi Poerwono ◽  
Siswandono Siswodiharjo
Keyword(s):  
Androgen Receptor ◽  
Cytotoxic Activity ◽  
Blood Brain Barrier ◽  
Inhibitory Activity ◽  
Water Solubility ◽  
Nitro Derivative ◽  
Total Clearance ◽  
Distribution Parameters ◽  
Trifluoromethyl Derivative ◽  
Class Iv

Abstract Background Prediction of the properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET) from a compound is essential, especially for modified novel compounds. Previous research has successfully designed several modified compounds of 5-O-benzoyl derivatives from pinostrobin, a flavanone that has cytotoxic activity. This study aims to describe the properties of ADMET from the 5-O-benzoylpinostrobin derivative. Methods Prediction of the properties of ADMET was carried out using three web servers consisting of SwissADME, pkCSM, and ProTox-II. The observed parameters are divided into ADMET parameters. Results In general, absorption parameters indicate that the 5-O-benzoylpinostrobin derivative has lower water solubility than the parent pinostrobin. Distribution parameters show mixed results for distribution through the blood-brain barrier. Metabolism parameters showed different results with generally inhibitory activity shown in CYP2C19, CYP2C9, and CYP3A4. The excretion parameters showed a higher total clearance than pinostrobin except in the trifluoromethyl derivative. The toxicity parameters showed both pinostrobin and the 5-O-benzoylpinostrobin derivatives, including the class IV toxicity category with the lowest LD50 value indicated by the nitro derivative of 1500, with the possible target of the androgen receptor and prostaglandin G/H synthase 1. Conclusions Overall, the 5-O-benzoylpinostrobin derivative has the predicted ADMET profile that is relatively similar to pinostrobin, with the most noticeable difference being shown in the absorption parameters where all 5-O-benzoylpinostrobin derivatives have lower water solubility than pinostrobin.

Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (9) ◽  
pp. 2069-2094 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Reaction Pathway ◽  
Sodium Hydride ◽  
Amino Group ◽  
Trimethylsilyl Derivative ◽  
Phosphonic Acids ◽  
Alkyl Derivatives ◽  
Hydrolysis Of ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of ◽  
Related Compounds

To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI. After protection of the adenine amino group by benzoylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with diisopropyl p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters XII were converted into phosphonic acids I by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives. The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 2,6-Diaminopurine derivatives XVIIId and XXIIb were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Derivatives of 11H-dibenz[b,f]-1,4-oxathiepin

1982 ◽  
Vol 47 (3) ◽  
pp. 967-983 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
Jiřina Metyšová ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Sodium Hydride ◽  
Sulfuryl Chloride ◽  
Side Chains ◽  
Central Ring ◽  
Lithium Compounds ◽  
Psychotropic Agents ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of

Reactions of 2-bromobenzyl bromide and its analogues XVII and XXV with 2-hydroxythiophenol resulted in 11H-dibenz[b,f]-1,4-oxathiepin (Ia) and its 2-chloro (Ib) and 2-trifluoromethyl derivative (IC). Treatment of the lithium compounds derived from Ia and Ib with carbon dioxide and dimethylaminoalkyl chlorides gave compounds IIa, Va and VIab; modification of side chains led to amines IVa, VIIa and VIIIa. 11-(1-Methyl-4-piperidyl) derivatives Xbc were obtained by chlorination of compounds Ibc with sulfuryl chloride or N-chlorosuccinimide and the following treatment with 1-methyl-4-piperidylmagnesium chloride. Compound Ib was transformed by oxidation to the sulfone XX affording by treatment with sodium hydride and tert-aminoalkylchlorides the basic sulfones XXI and XXII. While the nuclearly unsubstituted amines with the aliphatic side chains (IVa and VIIa) have intensive antireserpine activity and are potential antidepressants, the 11-(1-methyl-4-piperidyl) derivatives with a substituent in position 2 of the skeleton (Xbc) are potential neuroleptics; the trifluoromethyl derivative Xc especially has outstanding cataleptic and antiapomorphine efficacy.

Isolation and crystal structure of the trifluoromethyl derivative C84(24)(CF3)18 of a minor C84 fullerene isomer

2020 ◽  
Vol 30 (4) ◽  
pp. 474-475
Author(s):  
Nadezhda B. Tamm ◽  
Victor A. Brotsman ◽  
Sergey I. Troyanov
Keyword(s):  
Crystal Structure ◽  
A Minor ◽  
Trifluoromethyl Derivative

scholarly journals Interaction of 2,6,7-Trihydroxy-Xanthene-3-Ones with Iron and Copper, and Biological Effect of the Most Active Derivative on Breast Cancer Cells and Erythrocytes

2020 ◽  
Vol 10 (14) ◽  
pp. 4846
Author(s):  
Přemysl Mladěnka ◽  
Jana Karlíčková ◽  
Marcel Hrubša ◽  
Elma Veljović ◽  
Samija Muratović ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Copper Toxicity ◽  
Breast Adenocarcinoma ◽  
Metal Chelators ◽  
Iron Copper ◽  
Xanthene Derivatives ◽  
Copper Chelator ◽  
Trifluoromethyl Derivative ◽  
Positive Effect

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.

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