- Synthesis of N-trifluoromethyl amides from carboxylic acids
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Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
- Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
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supporting information
p. 2245 - 2255
(2021/08/12)
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- Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
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An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
- Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
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supporting information
p. 17887 - 17896
(2020/08/19)
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- Synthesis and molecular docking studies of some novel antimicrobial benzamides
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Common use of classical antibiotics has caused to the growing emergence of many resistant strains of pathogenic bacteria. Therefore, we aimed to synthesize a number of N-(2-hydroxy-(4 or 5)-nitrophenyl)benzamide derivatives as a new class of antimicrobial compounds. Moreover, our second goal is to predict the interaction between active structures and enzymes (DNA –gyrase and FtsA) in the binding mode. In this study, thirteen N-(2-hydroxy-(4 or 5-nitrophenyl)-substituted-benzamides were synthesized and determined for their antimicrobial activity using the microdilution method. According to this work, none of the compounds showed any activity against Candida albicans and its clinical isolate. Some of the benzamides (4N1, 5N1, 5N2) displayed very significant activity against Staphylococcus aureus and MSSA with 4 μg/ml MIC value, even they were found to be more potent than ceftazidime. 4N1 was also found to be more effective than gentamicin against Enterococcus faecalis clinical isolate. Molecular docking studies revealed that 4N1, 5N1, and 5N2 showed a good interactions with DNA-gyrase. Moreover, 5N1 has interacted with FtsA enzyme in the binding mode, as well. Only compound 5N4 displayed very good activity against Escherichia coli ATCC 25922. These findings showed us that 4N1, 5N1, 5N2, and 5N4 could be lead compounds to discover new antibacterial candidates against multidrug-resistant strains.
- Acar, Cemre,Yal??n, Gozde,Ertan-Bolelli, Tu?ba,Kaynak Onurda?, Fatma,?kten, Suzan,?ener, Funda,Y?ld?z, ?lkay
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- Wavelength-Orthogonal Photocleavable Monochromophoric Linker for Sequential Release of Two Different Substrates
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A wavelength-orthogonal photocleavable monochromophoric linker was developed that is based on a 3-acetyl-9-ethyl-6-methylcarbazole (AEMC) moiety substituted at both the phenacyl and benzylic positions with different carboxylic acids. The different carboxylic acids were released sequentially upon irradiation with light of λ ≥ 365 nm and λ ≥ 290 nm, respectively.
- Venkatesh, Yarra,Chaudhuri, Amrita,Mondal, Saugat,Shah, Sk. Sheriff,Singh, N. D. Pradeep
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p. 295 - 299
(2020/01/02)
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- Copper-mediated C–H thiolation of (hetero)arenes using weakly coordinating directing group
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We have developed a copper-mediated C–H thiolation of (hetero)arenes by using monodentate amide as weakly coordinating directing group. This protocol features excellent functional group tolerance and shows satisfactory compatibility with various heterocycles, such as indole, pyrrole, imidazole, pyridine, thiophene and quinoline. The robust nature of this protocol renders that it has potential value in the synthetic application.
- Wu, Peng,Cheng, Tai-Jin,Lin, Hai-Xia,Xu, Hui,Dai, Hui-Xiong
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supporting information
(2020/06/17)
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- Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase
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The cholinesterase enzymes play a vital role in maintaining balanced levels of the neurotransmitter acetylcholine in the central nervous system. However, the overexpression of these enzymes results in hampered neurotransmission. Both the major forms of cholinesterase enzymes viz. acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play a crucial role in blocking neurotransmission; therefore, in recent years, a strategy of dual cholinesterase inhibition is being explored. Herein, we developed an energy-optimized e-pharmacophore hypothesis AHHPRR from AChE-donepezil complex and screened a set of 15 scaffolds that were designed imaginarily. The ligand with N-(1-benzylpyridinium) benzamide framework has shown the highest fitness and volume score, which was chosen for synthesis and validation. A series of pyridinium benzamides were synthesized and screened for cholinesterase inhibition that led to the identification of 7b, a naphthalene containing N-(1-benzylpiperidine) benzamide as a potent dual AChE and BChE inhibitor with IC50 values of 0.176, and 0.47 μM, respectively. The kinetic study indicated that 7b inhibits AChE in a non-competitive manner with Ki value of 0.21 μM, and BChE in a mixed-fashion with Ki of 0.15 μM. The observed mode of inhibition was corroborated with molecular docking studies. The MD simulation studies pointed out that both AChE and BChE undergo low conformational changes in complex with 7b. The benzamide 7b displayed high BBB permeability in PAMPA assay, which indicates its potential for further exploration in preclinical studies for Alzheimer's disease.
- Abdullaha, Mohd,Bharate, Sandip B.,Nuthakki, Vijay K.
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- Probing the effects of the number and positions of –OCH3 and –CN substituents on color tuning of Ir(III) complex derivatives through a joint computational and experimental study
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We performed a joint theoretical and experimental study on sixteen Ir(III) complexes bearing a similar molecular platform of bis(2-phenylbenzothiozolato-N,C2’) iridium(III) (acetylacetonate) by grafting – OCH3 group and/or – CN group on different positions of the C-related arene moiety of the C^N ligand (Cring). Our results reveal that the introduction of – CN renders an overall drop in the FMO energy levels while a reverse increase is observed for – OCH3. The ortho- and para-sites of the C-ring are more effective substitution positions to modulate the HOMO energy level due to the fact that the electronic density of HOMO mainly locates at them while the meta-site would induce a stronger impact on LUMO since the electronic density of LUMO mainly distributes over the position. Utilizing the synergistic effects of the substituents and the substituted positions, a wide color-tuning range from 479 nm to 637 nm was achieved, which covers nearly the whole window of visible spectrum. In particular, the tri-substituted Ir35mo4cn complex (λemmax=637 nm) may be a potential candidate for high efficiency red OLEDs materials due to its greatly enhanced absorption processes, relatively higher3MLCT (%), lower ΔES1–T1, enlarged separation between3MLCT/π–π* and3MC d–d states, and good hole and particle-transporting performances. Finally, six representative complexes were synthesized and their spectra were determined, which confirm the reliability of our computational strategy.
- Qin, Xiao,Li, Ming,Xiang, Minghui,Luo, Yi,Jiao, Yan,Yuan, Rongao,Wang, Ning,Lu, Zhiyun,Pu, Xumei
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p. 470 - 481
(2019/06/03)
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- Ligand-Promoted RhIII-Catalyzed Thiolation of Benzamides with a Broad Disulfide Scope
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A ligand-promoted RhIII-catalyzed C(sp2)?H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII-catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.
- Kang, Yan-Shang,Zhang, Ping,Li, Min-Yan,Chen, You-Ke,Xu, Hua-Jin,Zhao, Jing,Sun, Wei-Yin,Yu, Jin-Quan,Lu, Yi
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supporting information
p. 9099 - 9103
(2019/06/13)
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- Probing the Effects of the Number and Positions of ?OCH3 and ?CN Substituents on Color Tuning of Ir(III) Complex Derivatives through a Joint Computational and Experimental Study
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We performed a joint theoretical and experimental study on sixteen Ir(III) complexes bearing a similar molecular platform of bis(2-phenylbenzothiozolato-N,C2’) iridium(III) (acetylacetonate) by grafting ?OCH3 group and/or ?CN group on different positions of the C-related arene moiety of the (Formula presented.) ligand (C-ring). Our results reveal that the introduction of ?CN renders an overall drop in the FMO energy levels while a reverse increase is observed for ?OCH3. The ortho- and para-sites of the C-ring are more effective substitution positions to modulate the HOMO energy level due to the fact that the electronic density of HOMO mainly locates at them while the meta-site would induce a stronger impact on LUMO since the electronic density of LUMO mainly distributes over the position. Utilizing the synergistic effects of the substituents and the substituted positions, a wide color-tuning range from 479 nm to 637 nm was achieved, which covers nearly the whole window of visible spectrum. In particular, the tri-substituted Ir35mo4cn complex (λem max=637 nm) may be a potential candidate for high efficiency red OLEDs materials due to its greatly enhanced absorption processes, relatively higher 3MLCT (%), lower ΔES1–T1, enlarged separation between 3MLCT/π–π* and 3MC d–d states, and good hole and particle-transporting performances. Finally, six representative complexes were synthesized and their spectra were determined, which confirm the reliability of our computational strategy.
- Jiao, Yan,Li, Ming,Lu, Zhiyun,Luo, Yi,Pu, Xumei,Qin, Xiao,Wang, Ning,Xiang, Minghui,Yuan, Rongao
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p. 470 - 481
(2019/01/10)
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- Preparation method of 3,5-dimethoxybenzoyl chloride
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The invention provides a preparation method of 3,5-dimethoxybenzoyl chloride and belongs to the technical field of medical technology. The technical problem to be solved by the invention is to providea preparation method of more advanced 3,5-dimethoxybenzoyl chloride. The key point of the technical scheme of the technical problem to be solved by the invention is characterized by providing a novelpreparation method of the compound which is 3,5-dimethoxybenzoyl chloride. The structure formula of 3,5-dimethoxybenzoyl chloride is as shown in the description.
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Paragraph 0007; 0008; 0009; 0010
(2018/12/13)
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- Facile synthesis of 3(2H)-furanones
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Abstract: A practical method for the synthesis of 3(2H)-furanones including the bullatenone was described. Intramolecular cyclization of 4-hydroxyalkynones in the presence of KOH affords the biologically potent furanones in moderate-to-good yield at room temperature. Synthesis of 4-hydroxyalkynones from the reaction of acid chloride and terminal alkyne in the presence of copper iodide at room temperature was also reported.
- Panda, Niranjan,Nayak, Dinesh K.
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p. 1093 - 1100
(2018/02/22)
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- Synthesis method of resveratrol
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The invention provides a synthesis method of resveratrol, and belongs to the technical field of natural product synthesis. The synthesis method comprises the following steps: with 3,5-dimethoxy benzoic acid as a raw material, generating 3,5-dimethoxy benzoyl chloride (12) through an acylating chlorination reaction; generating 3,5-dimethoxy benzamide (13) through an amidation reaction of the (12);generating 3,5-dimethoxyaniline (14) through a Hofmann degradation reaction of the (13); generating 3,5-dimethoxy iodobenzene (15) through a Sandmeyer reaction on the (14); generating 3,5,4'-trimethoxy diphenylethene (31) through a reaction between the (15) and p-methoxystyrene (23), and performing demethylation of the (31) to finally obtain resveratrol (1), wherein total yield is 23.3%. Accordingto the method, the adopted reagent is cheap and easily available, aftertreatment is simple, and two expensive intermediates for Heck reaction are synthesized by adopting cheap raw materials. A new synthesis method is provided for synthesizing resveratrol.
- -
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Paragraph 0033; 0034
(2018/05/03)
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- Synthesis, biological evaluation and molecular docking studies of novel trimethoxy-ring derivatives as BRD4 inhibitors
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Background: Bromodomain-containing protein 4 (BRD4) inhibitors synthesized with trimethoxy-ring refer to a new series of small molecular inhibitors. Currently, BRD4 offers the potential for research as a cancer therapeutic target. Based on previous studies, 17 trimethoxy-ring derivatives were designed as novel BRD4 inhibitors. Methods: All these new compounds were synthesized via the amide reaction. Their structures were identified by 1H NRM,13C NRM spectra and HRMS. In vitro antitumor activities of the new compounds were evaluated by MTT. Molecular docking studies were conducted to explain the binding interactions of these compounds with BRD4 protein. Results: A series of novel trimethoxy-ring derivatives were synthesized as BRD4 inhibitors and screened by testing their inhibition against HCT116, MCF-7, K562 and KMS-1 cell lines. Most of the newly synthesized compounds exhibited moderate-to-good inhibitory activity against HCT116, MCF-7, and K562 cell lines, whereas some showed inhibitory activity against the KMS-1 cell line. Conclusion: Compound 3g demonstrated the most potent anti-tumor activity against breast (MCF-7), leukemia (K562), multiple myeloma (KMS-1), and colon cancer (HCT116) cell lines.
- Yang, Yan,Yao, Zhiyi
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p. 1319 - 1328
(2018/11/01)
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- The Conversion of tert-Butyl Esters to Acid Chlorides Using Thionyl Chloride
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The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in unpurified yields of 89% or greater. Benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive under these conditions, allowing for the selective conversion of tert-butyl esters to acid chlorides in the presence of other esters.
- Greenberg, Jacob A.,Sammakia, Tarek
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p. 3245 - 3251
(2017/03/23)
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- PROCESS FOR THE PRODUCTION OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL
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The present disclosure relates to the preparation of a cannabidiol compound or a derivative thereof. The cannabidiol compound or derivatives thereof can be prepared by an acid-catalyzed reaction of a suitably selected and substituted di-halo-olivetol or derivative thereof with a suitably selected and substituted cyclic alkene to produce a dihalo-cannabidiol compound or derivative thereof. The dihalo-cannabidiol compound or derivative thereof can be produced in high yield, high stereospecificity, or both. It can then be converted under reducing conditions to a cannabidiol compound or derivatives thereof.
- -
-
Paragraph 0215; 0216; 0217
(2017/01/31)
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- C-F bond cleavage enabled redox-neutral [4+1] annulation via C-H bond activation
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Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
- Wang, Cheng-Qiang,Ye, Lu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 1762 - 1765
(2017/02/15)
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- Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d]pyrimidine Derivatives Containing ElectrophilicWarheads
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Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC50 values of 1.4 μM, 1.2 μM, 0.6 μM, and 2.6 μM, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-Activity relationship analysis was discussed based on the experimental data.
- Zhang, Qiumeng,Hu, Zonglong,Shen, Qianqian,Chen, Yi,Lu, Wei
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- Difluoromethylation of carboxylic acids via the addition of difluorinated phosphorus ylide to acyl chlorides
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A one-step protocol for the difluoromethylation of carboxylic acids is described. The reaction involves the interaction of intermediate acyl chlorides with in situ generated difluorinated phosphorus ylide Ph3P=CF2. Aromatic acids can be selectively transformed within one step either to bis-difluoromethylated alcohols or to difluorinated ketones depending on the particular reaction conditions. For bulky α-branched carboxylic acids, only ketones are produced.
- Trifonov, Alexey L.,Levin, Vitalij V.,Struchkova, Marina I.,Dilman, Alexander D.
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supporting information
p. 5304 - 5307
(2017/11/06)
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- Modulating lipophilicity of rohitukine via prodrug approach: Preparation, characterization, and in vitro enzymatic hydrolysis in biorelevant media
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Rohitukine is a medicinally important natural product which has inspired the discovery of two anticancer clinical candidates. Rohitukine is highly hydrophilic in nature which hampers its oral bioavailability. Thus, herein our objective was to improve the drug-like properties of rohitukine via prodrug-strategy. Various ester prodrugs were synthesized and studied for solubility, lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. All prodrugs displayed lower aqueous solubility and improved lipophilicity compared with rohitukine, which was in accordance with the criteria of compounds in drug-discovery. The stability of synthesized prodrugs was evaluated in buffers at different pH, SGF, SIF, rat plasma and in esterase enzyme. The rate of hydrolysis in all incubation media was dependent primarily on the acyl promoieties. Hexanoyl ester prodrug of rohitukine, 3d, was stable under chemical conditions; however it was completely hydrolyzed to rohitukine, in plasma and in esterase in 4?h. Hexanoate ester 3d appeared to be the most promising prodrug as it remained intact at gastric/intestinal pH and was completely transformed to the parent compound in plasma as desired for an ideal prodrug. The data presented herein, will help in designing prodrugs with desired physicochemical properties in future in structurally similar chemotypes.
- Kumar, Vikas,Bharate, Sonali S.,Vishwakarma, Ram A.
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p. 203 - 211
(2016/07/25)
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- Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication
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A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D-QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (S?) increase the anti-HBV activities of the arylpropenamide molecules. Predictive 3D-QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.
- Min, Ma,Xingjun, Jiang,Xueding, Wang,Hao, Zou,Weiqing, Yang,Yuanyuan, Zhang,Changrong, Peng,Zicheng, Li,Jing, Yang,Quan, Du,Menglin, Ma
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p. 451 - 459
(2016/10/19)
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- The Design, Synthesis, and Evaluation of 1,5,7-Trisubstituted-3-Pyridyl-Xanthones for Use as Insecticides Starting from Pyripyropene A
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A readily accessible template of 1,5,7-trisubstituted-3-pyridyl-xanthones was designed starting from naturally occurring pyripyropene A for agrichemical development. Our originally developed Ag2CO3-mediated oxidative cyclization enabled ready access to the key scaffold, 1,5,7-trihydroxy-3-chloro-xanthone. The chemo- and regioselective sequential introduction of four substituents to the scaffold rapidly afforded the desired, structurally diverse 1,5,7-trisubstituted-3-pyridyl-xanthones. An evaluation of insecticidal activity revealed that one of the synthesized compounds retained insecticidal activity against vetch aphid and green peach aphid. The observed insecticidal spectrum was similar to that of pyripyropene A. The developed template could be a valuable aid for future agrichemical development.
- Fuse, Shinichiro,Matsumura, Keisuke,Johmoto, Kohei,Uekusa, Hidehiro,Tanaka, Hiroshi,Hirose, Tomoyasu,Sunazuka, Toshiaki,ōmura, Satoshi,Takahashi, Takashi
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supporting information
p. 18450 - 18455
(2016/12/16)
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- Dicarbonyl chelates from 1-cymantrenylalkylamides with the dendrite structure: formation, photochromism, and kinetics of dark reaction with carbon monoxide
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Photolysis of carboxamides of the dendrite structure with aminomethyland 1-aminoethylcymantrenes leads to the formation of six-membered dicarbonyl chelates with the Mn—O bond which are stable in solutions. The chelates in the reversed dark reaction with carbon monoxide give the starting tricarbonyl complexes. The formation of the chelates and their dark reaction are accompanied by the reversible change of color by the compounds. The rate determining step of the thermal reaction of chelates with CO is a chelate ring opening with the ligand substitution by the SN1 mechanism. A possibility of solvent-free photoinduced ligand-exchange reaction in a number of cymantrene derivatives was demonstrated.
- Kelbysheva,Telegina,Abramova,Strelkova,Ikonnikov,Rodionov,Ezernitskaya,Lokshin,Loim
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p. 2646 - 2654
(2016/10/03)
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- Syntheses, third-order optical nonlinearity and DFT studies on benzoylferrocene derivatives
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A series of benzoylferrocene derivatives were synthesized and their third-order nonlinear optical (NLO) properties were evaluated in N,N-dimethyl-formamide at 800 nm using femtosecond degenerate four-wave mixing. The third-order NLO susceptibilities of synthesized compounds were 3.065-7.859 × 10-13 esu, with the response times in 49-70 fs. The second-order hyperpolarizabilities of the molecules of the compounds were 1.018-2.611 × 10-31 esu. The Density Functional Theory was used to calculate these benzoylferrocene derivatives. The theoretical study showed that the third-order NLO properties were increased with the increasing electron-withdrawing ability, which is accordance with the decreasing energy gap between the highest occupied and the lowest unoccupied molecular orbital. With the increasing of electron-withdrawing ability, the transferred charge to the substituent was increased and the affection on the electronic reallocate was increased. The experiment and theoretical results showed that the benzoylferrocene derivatives had potential nonlinear optical applications.
- Jia, Jianhong,Cui, Yanhong,Han, Liang,Sheng, Weijian,Li, Yujin,Gao, Jianrong
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p. 137 - 145
(2014/02/14)
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- Crystal structures of PI3Kα complexed with PI103 and its derivatives: New directions for inhibitors design
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The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3Kα-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3Kα-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3Kα inhibitors.
- Zhao, Yanlong,Zhang, Xi,Chen, Yingyi,Lu, Shaoyong,Peng, Yuefeng,Wang, Xiang,Guo, Chengliang,Zhou, Aiwu,Zhang, Jingmiao,Luo, Yu,Shen, Qiancheng,Ding, Jian,Meng, Linghua,Zhang, Jian
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supporting information
p. 138 - 142
(2014/03/21)
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- Novel N-acyl/aroyl-2-(5-phenyl-2H-tetrazol-2-yl)acetohydrazides: Synthesis and characterization
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A number of novel N -acyl/aroyl-2-(5-phenyl-2H-tetrazol-2-yl) acetohydrazides (4a-j) of biological interest were efficiently synthesized by treating 2-(5-phenyl-2H-tetrazole-2-yl)acetohydrazide (3) with a variety of aroyl/heterocyclyl or alkanoyl chlorides. FTIR, 1H NMR, 13C NMR, GC-MS, and elemental analyses data confirmed the structures assigned to the newly synthesized compounds. TUeBITAK.
- Saeed, Aamer,Hussain, Majid,Qasim, Muhammad
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p. 436 - 442
(2014/06/09)
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- Synthesis, antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives
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A series of 2-arylbenzimidazole derivatives (3a-3p and 4a-4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O2 -) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC50 = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H2O2-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.
- Zhou, Binhua,Li, Baojian,Yi, Wei,Bu, Xianzhang,Ma, Lin
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supporting information
p. 3759 - 3763
(2013/07/27)
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- Design, synthesis, biological and structural evaluation of functionalized resveratrol analogues as inhibitors of quinone reductase 2
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Resveratrol (3,5,4′-trihydroxylstilbene) has been proposed to elicit a variety of positive health effects including protection against cancer and cardiovascular disease. The highest affinity target of resveratrol identified so far is the oxidoreductase enzyme quinone reductase 2 (QR2), which is believed to function in metabolic reduction and detoxification processes; however, evidence exists linking QR2 to the metabolic activation of quinones, which can lead to cell toxicity. Therefore, inhibition of QR2 by resveratrol may protect cells against reactive intermediates and eventually cancer. With the aim of identifying novel inhibitors of QR2, we designed, synthesized, and tested two generations of resveratrol analogue libraries for inhibition of QR2. In addition, X-ray crystal structures of six of the resveratrol analogues in the active site of QR2 were determined. Several novel inhibitors of QR2 were successfully identified as well as a compound that inhibits QR2 with a novel binding orientation.
- St. John, Sarah E.,Jensen, Katherine C.,Kang, Soosung,Chen, Yafang,Calamini, Barbara,Mesecar, Andrew D.,Lipton, Mark A.
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p. 6022 - 6037
(2013/09/23)
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- Synthesis of B-ring substituted flavones and evaluation of their antitumor and antioxidant activities
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A series of flavones, substituted at the ring B, were synthesized using either Claisen-Schimdt Condensation or Baker-Venkataraman rearrangement. The synthesized compounds were tested for in vitro cytotoxic activity by sulforhodamine B assay against three cell lines of different origin, viz. HepG2, MCF-7, and MOLT-4. The compounds were also tested for a possible antioxidant activity by determination of inhibition of lipid peroxidation. Quercetin was taken as a standard for antioxidant activity. Compound 1c showed the highest cytotoxic activity against MCF-7 (GI50 0.1 μM) and MOLT-4 (GI50 0.1 μM) cell lines and was comparable to adriamycin, the standard used. Compounds 1b, 1g, and 1h also showed promising activity against MCF-7 and MOLT-4 cell lines. In the absence of a hydroxyl group, one or more methoxy groups present on the B-ring (compounds 1c-1e) were major determinants of inhibition of lipid peroxidation.
- Joshi, Akshada J.,Gadhwal, Manoj K.,Joshi, Urmila J.,D'Mello, Priscilla,Sinha, Ragini,Govil, Girjesh
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p. 4293 - 4299
(2013/09/02)
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- Construction of hetero[n]rotaxanes by use of polyfunctional rotaxane frameworks
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Heterorotaxanes, one class of topological organic structures, have attracted increasing interesting during the past two decades. In general, two types of heterorotaxane structures exist, one in which two or more different macrocycles are threaded onto one dumbbell-shaped molecule and the other where one macrocycle is threaded onto two or more different dumbbell-shaped molecules. In comparison to these traditional types, another family of topologically interesting heterorotaxanes can be envisaged as arising from polyfunctional molecules that possess both host (crown ether) and guest (ammonium templates). In the present investigation, we have explored the construction of selected members of this new heterorotaxane family, which possess crown ether moieties that are wrapped around a dumbbell-shaped molecule. These structures are prepared by routes in which "stitching" processes, involving template-directed clipping reaction or olefin metathesis reactions, are used to install crown ether ring systems encircling ammonium cation centers. This is then followed by implementation of a threading-followed-by-stoppering sequence to install a second encircling crown ether ring. The results show that the polyfunctional building blocks assemble with high efficiencies. Finally, this investigation provides a foundation for future studies aimed at constructing more complicated heterorotaxane architectures, such as switchable systems, self-assembling polymers, and functional molecular machines.
- Li, Ziyong,Liu, Guoxing,Xue, Wen,Wu, Di,Yang, Ying-Wei,Wu, Jishan,Liu, Sheng Hua,Yoon, Juyoung,Yin, Jun
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p. 11560 - 11570
(2013/12/04)
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- Acylthiourea, acylurea, and acylguanidine derivatives with potent Hedgehog inhibiting activity
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The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.
- Solinas, Antonio,Faure, Hélène,Roudaut, Hermine,Traiffort, Elisabeth,Schoenfelder, Angèle,Mann, André,Manetti, Fabrizio,Taddei, Maurizio,Ruat, Martial
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body text
p. 1559 - 1571
(2012/04/17)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 15
(2012/11/08)
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- Synthesis and antimicrobial evaluation of new benzofuran derivatives
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Thirteen compounds, based on benzofuran skeleton bearing aryl substituents at its C-3 position through methanone linker, were synthesized and screened for their antibacterial and antifungal activities against four bacteria Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and a fungus Candida albicans. Four hydrophobic benzofuran analogs were found to exhibit favorable antibacterial activities (MIC80 = 0.39-3.12 μg/mL), which were better than the control drugs.
- Jiang, Xizhen,Liu, Wenlu,Zhang, Wei,Jiang, Faqin,Gao, Zhe,Zhuang, Hao,Fu, Lei
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experimental part
p. 3526 - 3530
(2011/07/31)
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- Synthesis and antibacterial activities of pleuromutilin derivatives with thiazole-5-carboxamide and thioether moiety
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Seven novel pleuromutilin derivatives with thiazole-5-carboxamide and thioether moiety in the C14 side chain were designed and synthesised. The antibacterial activities of the target compounds were tested via agar-well diffusion method in vitro. The results showed that three target compounds still had antibacterial activity against Staphylococcus aureus ATCC26112 and Staphylococcus aureus SC at a low concentration of 0.05 μg mL-1.
- Wang, Liang,Dai, Fu-Ying,Zhu, Jie,Dong, Kui-Kui,Wang, Yu-Liang,Chen, Tian
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experimental part
p. 313 - 316
(2011/10/05)
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- Antitrypanosomal activity of 1,2-dihydroquinolin-6-ols and their ester derivatives
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The current chemotherapy for second stage human African trypanosomiasis is unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with potent in vivo activity. While 6-ether derivatives were less active than the lead compound, several N1-substituted derivatives displayed nanomolar IC50 values against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to > 18000. 1-Benzyl-1,2-dihydro-2,2,4- trimethylquinolin-6-yl acetate (10a) displayed an IC50 value of 0.014 μM against these parasites and a selectivity index of 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice (>14 days vs 7.75 days for untreated controls). Reactive oxygen species were produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative stress in the trypanocidal mode of action of these 1,2-dihydroquinoline derivatives.
- Fotie, Jean,Kaiser, Marcel,Delfín, Dawn A.,Manley, Joshua,Reid, Carolyn S.,Paris, Jean-Marc,Wenzler, Tanja,Maes, Louis,Mahasenan, Kiran V.,Li, Chenglong,Werbovetz, Karl A.
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body text
p. 966 - 982
(2010/08/06)
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- Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-A kinase inhibitors
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Two series of 3-aminopyrazole compounds including 24 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and 16 pyrazolo[3,4-b]pyridines were synthesized and evaluated against HCT116, A549, and A2780 tumor cell lines. Among them, three compounds were found to have the ideal anti-proliferative activities in vitro. Docking experiments showed that the novel pyrazolo[3,4-b]pyridines share the similar interaction mode with Aurora-A kinase as PHA739358.
- Shi, Jianyou,Xu, Guobin,Zhu, Wei,Ye, Haoyu,Yang, Shengyong,Luo, Youfu,Han, Jing,Yang, Jincheng,Li, Rui,Wei, Yuquan,Chen, Lijuan
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supporting information; experimental part
p. 4273 - 4278
(2010/09/04)
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- 2,4,5-TRISUBSTITUTED THIAZOLE COMPOUNDS,PREPARATION METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICAL USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 41
(2009/04/23)
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- TRISUBSTITUTED THIAZOLE COMPOUNDS, PREPARATIONS METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICALS USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 29
(2009/12/23)
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- Synthesis and pharmacological screening of several aroyl and heteroaroyl selenylacetic acid derivatives as cytotoxic and antiproliferative agents
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The synthesis and cytotoxic activity of a series of twenty six aroyl and heteroaroyl selenylacetic acid derivatives of general formula Ar-CO-Se-CH2-COOH or Heterar-CO-Se-CH2-COOH are reported. The synthesis was carried out by reaction of acyl chlorides with sodium hydrogen selenide, prepared in situ, and this led to the formation of sodium aroylselenides that subsequently reacted with --bromoacetic acid to produce the corresponding selenylacetic acid derivatives. All of the compounds were tested against a prostate cancer cell line (PC-3) and some of the more active compounds were assessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54, HT-29, MCF-7) and one mammary gland-derived non-malignant cell line (184B5). Some of the compounds exhibited remarkable cytotoxic and antiproliferative activities against MCF-7 and PC-3 that were higher than those of the reference compounds doxorubicin and etoposide, respectively. For example, in MCF-7 when Ar=phenyl, 3,5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and 6.19 -M. On the other hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 -M. Furthermore, benzoylselenylacetic acid did not provoke apoptosis nor did it perturb the cell cycle in MCF-7.
- Sanmartin, Carmen,Plano, Daniel,Dominguez, Enrique,Font, Maria,Calvo, Alfonso,Prior, Celia,Encio, Ignacio,Palop, Juan Antonio
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scheme or table
p. 3313 - 3338
(2010/03/04)
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- Discovery and biological evaluation of novel cyanoguanidine P2X7 antagonists with analgesic activity in a rat model of neuropathic pain
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We disclose the design of a novel series of cyanoguanidines that are potent (IC50 ? 10-100 nM) and selective (≥100-fold) P2X7 receptor antagonists against the other P2 receptor subtypes such as the P2Y2, P2X4, and P2X3. We also found that these P2X7 antagonists effectively reduced nociception in a rat model of neuropathic pain (Chung model). Particularly, analogue 53 proved to be effective in the Chung model, with an ED50 of 38 μmol/kg after intraperitoneal administration. In addition compound 53 exhibited antiallodynic effects following oral administration and maintained its efficacy following repeated administration in the Chung model. These results suggest an important role of P2X7 receptors in neuropathic pain and therefore a potential use of P2X7 antagonists as novel therapeutic tools for the treatment of this type of pain.
- Perez-Medrano, Arturo,Donnelly-Roberts, Diana L.,Honore, Prisca,Hsieh, Gin C.,Namovic, Marian T.,Peddi, Sridhar,Shuai, Qi,Wang, Ying,Faltynek, Connie R.,Jarvis, Michael F.,Carroll, William A.
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scheme or table
p. 3366 - 3376
(2010/04/03)
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- An approach to an enantioselective synthesis of crisamicin A via a novel double Hauser-Kraus annulation strategy
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A double Hauser-Kraus annulation between biscyanophthalide 4 and the d-mannose derived enone 39 provides access to an advanced intermediate 54 that is an excellent scaffold to effect an enantioselective total synthesis of crisamicin A 1.
- Andrey, Olivier,Sperry, Jonathan,Larsen, Uffe S.,Brimble, Margaret A.
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p. 3912 - 3927
(2008/09/20)
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- BENZIMIDAZOLE DERIVATIVES
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The present invention relates to a compound of the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1,R2, R3, R4, R5, A, X, n, and are as defined herein. Such novel benzamidazole derivatives are useful in trv treatment of abnormal cell growth, such as cancer, in mammals. This invention ate relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing sue compounds.
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Page/Page column 87
(2008/12/06)
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- Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes
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CDPPB [3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide] was recently described as the first centrally active, positive allosteric modulator of rat and human metabotropic glutamate receptor (mGluR) mGluR5 subtype. We explored the structural requirements for potentiation of glutamate-induced calcium release in naturally expressed mGluR5 in cultured rat astrocytes and increasing affinity for the allosteric antagonist binding site by evaluating 50 analogues of CDPPB. In the fluorometric calcium assay, CDPPB exhibited an EC50 value of 77 ± 15 nM in potentiating mGluR 5-mediated responses in cortical astrocytes and a Ki value of 3760 ± 430 nM in displacing [3H]methoxyPEPy binding in membranes of cultured HEK-293 cells expressing rat mGluR5. The structure-activity relationships showed that electronegative aromatic substituents in the para-position of the benzamide moiety of CDPPB increase potency. Both binding and functional activities were further increased with a halogen atom in the ortho-position of the 1-phenyl ring. These effects of substitution do not match those of either aromatic ring of MPEP [2-methyl-6-(phenylethynyl)-pyridine] for the antagonist allosteric binding site. Combination of the optimal substituents and aromatic positions resulted in 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl)benzamide (VU-1545) showing Ki = 156 ± 29 nM and EC50 = 9.6 ± 1.9 nM in the binding and functional assays, respectively.
- De Paulis, Tomas,Hemstapat, Kamondanai,Chen, Yelin,Zhang, Yongqin,Saleh, Samir,Alagille, David,Baldwin, Ronald M.,Tamagnan, Gilles D.,Conn, P. Jeffrey
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p. 3332 - 3344
(2007/10/03)
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- A convenient synthesis of 14C-labelled resveratrol
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Resveratrol (trans-3,4′,5-trihydroxystilbene) is a naturally occurring phytoalexin and polyphenol existing in grapes and various plants. It shows remarkable beneficial bioactivities in the prevention of cancer, inflammation and platelet aggregation, etc. This paper reports the synthesis of [β-14C]-trans-resveratrol using 14C-formic acid (exchanged with sodium 14C-formate) and 3,5-dihydroxybenzoic acid as the starting materials. [14C-formyl]-4-methoxybenzaldehyde and diethyl 3,5-dimethoxy benzylphosphonate reacted following the Wittig-Horner reaction to give trans-3,4′,5-[β-14C]-trimethoxystilbene. The final product was obtained through the demethylation of trans-3,4′ ,5-[β-14C]-trimethoxystilbene and identified by TLC and UV spectroscopy. Adoption of the whole procedure provided 14C-resveratrol with a specific radioactivity of 40.8 μCi/mmol, chemical yield of 15.3% and radiochemical yield of 12.5%. Copyright
- Zeng, Dongli,Mi, Qixi,Sun, Hongfang,Wang, Haifang
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p. 167 - 174
(2007/10/03)
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- A convenient protocol for the synthesis of ligands from a 4-methyl-3,5-diacylaminophenyl platform
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The synthesis of stable and highly organized phenanthroline, terpyridine, and pyridino-oxazoline ligands bearing one or two 4-methyl-3,5-diacylaminophenyl modules equipped with two lateral dialkoxyphenyl groups has been performed using EDC·HCl and DMAP reagents in the final coupling reaction. Evidently, in the final ligands and in the solid state intermolecular hydrogen bonding maintains the coherence of the tridimensional structure as clearly evidenced by FT-IR and X-ray diffraction spectroscopy in the cases of the methoxy ligands. The supramolecular packing is also maintained by additional π-π stacking interactions.
- Pickaert, Guillaume,Cesario, Michele,Ziessel, Raymond
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p. 5335 - 5341
(2007/10/03)
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- Synthesis and HIV-1 reverse transcriptase inhibitor activity of some 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole and oxazolo (4,5-b)pyridine derivatives
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In this study, the synthesis of some benzoxazoles and their analogues were described and their antiviral activities were studied together with the previously synthesized 2,5,6-trisubstituted benzoxazole, benzothiazole, benzimidazole and oxazolo(4,5-b)pyridine derivatives. The reverse transcriptase (RT) inhibitory activity of these compounds was determined using a commercial kit and assay system which utilizes the scintillation proximity assay principle. The results are concentration at which the compound inhibits RT activity by 50%). The compounds inhibited the in vitro binding of thymidine to the RT enzyme exhibiting IC50 values between 6.3 × 105 μmol/l-0.34 μmol/l and their activities were compared to some standard drugs such as 3′-azido-2′,3′-dideoxythymidine triphosphate and dideoxythymidine triphosphate.
- Akbay, Ayseguel,Oeren, Ilkay,Temiz-Arpaci, Oezlem,Aki-Sener, Esin,Yalcin, Ismail
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p. 266 - 271
(2007/10/03)
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- α-amino acid derivatives by enantioselective decarboxylation
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The methodology of enantioselective decarboxylation was applied to 2-aminomalonic acid derivatives in order to obtain enantio-enriched amino acid derivatives. Full conversion was achieved stirring racemic N-acetylated 2-aminomalonic hemiesters in THF at 70 °C with 10 mol % of a chiral base for 24 h. The catalyst may be recycled. Whereas the commercially available cinchona alkaloids gave poor results, benzamide and benzenesulfonamide derivatives of 9-amino(9-deoxy)epicinchonine turned out to be effective catalysts. The best result was obtained with 2-N-acetylamino-2-ethoxy-carbonyl-3-phenylpropionic acid as the starting material and N-(9-deoxyepicinchonine-9-yl)-4-methoxybenzamide as the chiral base to give ethyl N-acetyl-L-phenylalaninate in 70% ee. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Brunner, Henri,Baur, Markus A.
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p. 2854 - 2862
(2007/10/03)
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- Synthesis and microbiological activity of some N-(2-hydroxy-4-substitutedphenyl)benzamides, phenylacetamides and furamides as the possible metabolites of antimicrobial active benzoxazoles
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The synthesis of some N-(2-hydroxy-4-substitutedphenyl)benzamides, phenylacetamides and furamides as the possible metabolites of benzoxazoles ( II(1-15)) was performed in order to determine their in vitro antimicrobial activity against three Gram-positive bacteria, two Gram-negative bacteria and the fungus Candida albicans and their activities were compared with several control drugs. The compounds II(11), II(12), and II(13) were found active at a MIC value of 12.5 μg/ml against the Gram-negative microorganism Pseudomonas aeruginosa. Most of the compounds show antibacterial activity at MIC a value of 25 μg/ml against the Gram-positive bacteria Staphylococcus aureus. For the antifungal activity against C. albicans, compound II(10) was found more active than the other derivatives. The antimicrobial activity of some of these benzamides, phenylacetamides (II(1) and II(10)) which are the possible metabolites of benzoxazoles, was also compared to their corresponding cyclic analogues III-IV. Compound II(10) possesses two dilutions better antifungal activity than its cyclic analogue, benzoxazole IV, against C. albicans.
- Aki-Sener, Esin,Bingoel, Kamuran K.,Temiz-Arpaci, Oezlem,Yalcin, Ismail,Altanlar, Nurten
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p. 451 - 456
(2007/10/03)
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- Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors
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A series of trans-stilbene derivatives containing a 3,5-dimethoxyphenyl moiety were prepared through a new efficient solution phase synthetic pathway, and their inhibitory activities were evaluated on human cytochrome P450s (CYP) 1A1, 1A2, and 1B1 to find a potent and selective CYP1B1 inhibitor. We found that a substituent at the 2-position of the stilbene skeleton plays a very important role in discriminating between CYP1As and CYP1B1. Among the compounds tested, the most selective and potent CYP1B1 inhibitor was 2,3',4,5'-tetramethoxystilbene. Compound 7j, 2-[2-(3,5-dimethoxy-phenyl)vinyl]thiophene, showed greater inhibitory activities but had a lower selectivity toward all of the CYPls tested.
- Kim,Ko,Jae Eun Park,Jung,Sang Kwang Lee,Chun
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p. 160 - 164
(2007/10/03)
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- Purine derivatives and medicinal use thereof
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A novel purine derivative exhibiting an effect to control inflammatory symptoms characteristic to nephritis and a medicine comprising this compound as an effective ingredient are provided. The compound is represented by the following general formula (I), wherein R1 is a hydrocarbon group having 17 or less carbon atoms and R2 is a hydrocarbon group having 16 or less carbon atoms, wherein one or more CH2 g roups in the hydrocarbon group which 7013 do not directly bind with the carbon atom at 2 or 7 position of the purine ring replaced are by carbonyl groups, sulfonyl groups, O, or S and/or one or more CH groups in the hydrocarbon group which do not directly bind with the carbon atom at 2 or 7 position of the purine ring are replaced by N, C-halogen, or C—C≡N, or a pharmaceutically acceptable salt thereof.
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- Synthesis of arylspiroketals related to the papulacandins via generation of phthalide oxycarbenium ions
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The nucleophilic addition of allylstannanes to oxycarbenium ions generated from phthalide acetate has been studied. The optimum conditions involve the use of trimethylsilyl trifluoromethanesulfonate in dichloromethane at -78 °C. Hydroboration of the allylated products followed by oxidative cyclization provides an efficient synthesis of arylspiroketals which are closely related to the papulacandins.
- Brimble, Margaret A.,Caprio, Vittorio,Johnston, Andrew D.,Sidford, Matthew
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p. 855 - 862
(2007/10/03)
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