- Metal-Free Oxidative Condensation of Catechols, Aldehydes and NH4OAc towards Benzoxazoles
-
Benzoxazoles extensively exist in biologically active compounds, natural products, pharmaceuticals and functional materials. Thus, facile and green synthesis of such valuable compounds from easily available substrates will make a contribution to drug, material, and fine chemistry. A method for the synthesis of benzoxazoles from catechols, aldehydes and ammonium acetate is developed using NaIO4 as oxidant under metal- and additive-free conditions. A broad range of benzoxazoles including some fluorescent whitening agents, JTP-426467 and tafamidis analogues are synthesized in 56–95% yields with outstanding functional group tolerance. Mechanistic investigations suggest that an interesting o-iminocyclohexa-diene alcohol intermediate is involved in the reaction. These salient features of the protocol make it an alternative for the synthesis of benzoxazoles. (Figure presented.).
- Dong, Jianyu,Geng, Furong,Su, Lebin,Wu, Shaofeng,Yin, Shuang-Feng,Zhou, Dan,Zhou, Yongbo
-
supporting information
p. 3607 - 3614
(2021/07/28)
-
- Synthesis and structure-activity relationship studies of n-monosubstituted aroylthioureas as urease inhibitors
-
Background: Thiourea is a classical urease inhibitor which is usually used as a positive control, and many N,N'-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N'-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thiourea with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated via surface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11, and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in the intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed an IC50 value of 0.060 ± 0.004μM against cell-free urease, which bound to urea binding site with a very low KD value (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11 was also demonstrated to have very low cytotoxicity to mammalian cells. Conclusion: The results revealed that N-monosubstituted aroylthioureas bound to the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by urease-containing pathogens.
- Dawalamu,Fang, Hai-Lian,Fu, Zi-Juan,Li, Fang,Li, Ke,Li, Wei-Yi,Liu, Li,Ni, Wei-Wei,Ouyang, Hui,Xiao, Zhu-Ping,Ye, Ya-Xi,Zhu, Hai-Liang,Zhu, Wen-Yan,Zou, Xia
-
p. 1046 - 1059
(2021/11/30)
-
- 2-Aminopyrazine-functionalized MCM-41 nanoporous silica as a new efficient heterogeneous ligand for Cu-catalyzed allylic C–H bonds oxidation of olefins
-
In spite of the importance of the application of allylic C–H bond oxidation of olefins in organic synthesis and existence of the numerous reports, lots of limitations such as large excess of the olefin respect to the oxidant, low chemical yield, long time of reaction and a large amount of the catalyst were reminded. We introduced a novel catalytic system using functionalized MCM-41 as catalyst support to promote efficiency of this reaction. The heterogeneous ligand Pyr-MCM-41 was prepared by substituted 2-aminopyrazine ligand on functionalized MCM-41 with 3-chloropropyltrimthoxysilane and characterized by FT-IR, XRD, SEM, EDX, BET, TGA, CHN techniques. In situ immobilized Pyr-MCM-41 by copper (I) trifluoromethanesulfonate (CuOTf) was applied in direct catalytic esterification of inert C–H bonds in olefins using various peresters at room temperature.
- Samadi, Saadi,Ashouri, Akram,Kamangar, Shadi,Pourakbari, Fatemeh
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p. 557 - 569
(2019/11/03)
-
- Synthesis and Antiproliferative Activities of Novel Substituted 5-Anilino-α-Glucofuranose Derivatives
-
In order to find novel antitumor candidate agents with high efficiency and low toxicity, 14 novel substituted 5-anilino-α-glucofuranose derivatives have been designed, synthesized and evaluated for antiproliferative activities in vitro. Their structures were characterized by NMR (1H and 13C) and HR-MS, and configuration (R/S) at C(5) was identified by two-dimensional 1H,1H-NOESY-NMR spectrum. Their antiproliferative activities against human tumor cells were investigated by MTT assay. The results demonstrated that most of the synthesized compounds had antiproliferative effects comparable to the reference drugs gefitinib and lapatinib. In particular, (5R)-5-O-(3-chloro-4-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}anilino)-5-deoxy-1,2-O-(1-methylethylidene)-α-glucofuranose (9da) showed the most potent antiproliferative effects against SW480, A431 and A549 cells, with IC50 values of 8.57, 5.15 and 15.24 μm, respectively. This work suggested 5-anilino-α-glucofuranose as an antitumor core structure that may open a new way to develop more potent anti-cancer agents.
- Hou, Qiaoli,Li, Baolin,Li, Xiabing,Sun, Baoli,Wang, Lili,Wang, Wei,Zhang, Yaling
-
-
- Preparation method and application of antibacterial drugs
-
The invention provides phosphite ester compounds with an antibacterial effect and represented by a general formula I, a preparation method of the compounds, an application of the compounds in antibacterial drugs and pharmaceutical compositions containing the compounds. The ten synthesized compounds are novel in structure, the antibacterial activity of the compounds is equivalent to or even superior to that of positive control clindamycin and ciprofloxacin, the antibacterial spectrum is wide, and the compounds 5 and 10 are particularly expected to be further developed into antibacterial activedrugs.
- -
-
Paragraph 0030-0034
(2020/05/02)
-
- Comprising benzimidazole structure of sulfonamide derivatives and its preparation and use
-
The invention belongs to the field of medical technology, discloses benzimidazole structure of sulfonamide derivatives and its preparation method and application. The derivatives of formula I as shown in the structural formula, in formula I, R1 , R2 , R3 , R4 , X such as the claim and the specification. The compounds of the invention has better anti-tumor activity, can be used as a therapeutic agent for the treatment of tumor, it is also SMO inhibitors. (Type I).
- -
-
Paragraph 0066-0068
(2019/07/04)
-
- Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors
-
A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC50 = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.
- Hou, Weijie,Ren, Yan,Zhang, Zhenhua,Sun, Huan,Ma, Yongfen,Yan, Bo
-
p. 1740 - 1750
(2018/03/12)
-
- N - 3 - benzimidazole thiazole derivative and its preparation method and application
-
The invention discloses a new compound N-3-benzimidazole thiazole amine derivative and a preparation method and application thereof. A structural formula of the compound is shown as in figure I, and in the figure I, R1 is morpholinyl, piperidyl, N-methyl piperazinyl, N-arylpiperazine, diethylin, ethyoxyl, (dimethoxy)ethylamino, or R1 is one of mono-substituted or multi-substituted aniline on the following benzene ring: fluorine, chlorine, trifluoromethoxyl, methyl, methoxyl, hydroxyl group, nitryl, amino group, acetamido, trifluoromethyl and cyano group. The compound disclosed by the invention has better antineoplastic activity, and can be used as a therapeutic agent for treating a tumor in the field of antineoplastic drug preparation.
- -
-
Paragraph 0028; 0029-0031
(2018/06/04)
-
- Nicotinamide derivative and preparation method and application thereof
-
The invention discloses a novel compound N-3-(4-R2 substituted)-(1-R-substituted benzimidazole)-(1'-R3 substituted)-2'-oxa-nicotinamide derivative, and a preparation method and an application thereof.The structural formula of the compound is as shown in a formula I, in which R1, R2 and R3 are described in the claims and description. The compound has very good anti-diabetes activity, and can be used as therapeutic agent for treating diabetes in the field of preparing anti-diabetes drugs. The formula is as shown in the description.
- -
-
Paragraph 0060; 0062; 0064
(2018/07/30)
-
- Synthesis and antibacterial evaluation of 3,5-Diaryl-1,2,4-oxadiazole derivatives
-
This manuscript reports the synthesis of twenty 3,5-diaryl-1,2,4-oxadiazole derivatives, nine of which are novel compounds. The amidoxime reaction with acyl chlorides obtained from substituted benzoic acids was used. All compounds were tested against five standard (American Type Culture Collection (ATCC)) bacteria: Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis and Staphylococcus aureus. Screening assays were carried out using agar-diffusion technique, in which 100 μM heterocyclic compounds solutions (20percent dimethylsulfoxide/water) were employed. The minimum inhibitory concentrations (MIC) of the active compounds were determined by serial dilutions at decreasing concentrations in microtiter plates. The nitrated derivatives gave the best test results, where MIC = 60 μM (E. coli) was the lowest value found for an ortho-nitrated derivative. The activity of these compounds possibly involves a mechanism via free radicals. S. aureus and P. aeruginosa were resistant to all compounds.
- Cunha, Felipe S.,Nogueira, Joseli M. R.,De Aguiar, Alcino P.
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p. 2405 - 2416
(2018/10/20)
-
- Synthesis method for (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone
-
The invention discloses a synthesis method for (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone. According to the method, with cheap o-chlorobenzoic acid as a starting material, (2-chloro-5-iodophenyl)(4-fluorophenyl)ketone is obtained by nitration, Friedel-Crafts acylation and reduction and finally by Sandmeyer reaction for iodination. The materials used by the method are cheap and easy to obtain, and the method adopting Sandmeyer reaction for iodination can increase the iodine utilization rate, and has the characteristics of simplicity in operation, high yield, high purity and suitability for industrialized production. (The chemical formula is shown in the specification).
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-
-
- Diarylamino glucosan derivative, and preparation method and anti-tumor purpose thereof
-
The invention belongs to the field of medicinal chemistry, and particularly relates to a diarylamino glucosan derivative, and a preparation method and an anti-tumor purpose thereof, wherein the diarylamino glucosan derivative particularly relates to a compound shown as a formula I. The invention also relates to the preparation method of the diarylamino glucosan derivative, and the purpose of the diarylamino glucosan derivative in an aspect of preparing medicine for treating tumor diseases. The diarylamino glucosan derivative particularly has the obvious inhibition effects on human skin quamous cell carcinoma cells, human lung carcinoma cells and human colon cancer cells.
- -
-
Paragraph 0050; 0051; 0052; 0053; 0064; 0089
(2017/04/26)
-
- N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicine for treating diabetes
-
The invention discloses an N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicines for treating diabetes. The structural formula of the derivative is as shown in the specification, and in the formula, R1 is halogen or C1-C4 alkyl; R2 is substituted aryl; R3 is H or acyl with 1-4 atoms. The compound disclosed by the invention has functions of remarkably reducing blood sugar and promoting discharge of glucose from urea, and can be used for preparing medicines for treating diabetes.
- -
-
Paragraph 0128; 0129
(2017/07/18)
-
- 2-Halobenzoyl chlorides in the synthesis of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one derivatives
-
New nitro and sulfonamide derivatives of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one have been synthesized by cyclocondensation of 1,3,4-thiadiazol-2-amines with 2-halobenzoyl chlorides containing electron-withdrawing substituents in positions 3, 4, and 5. An improved procedure has been proposed for the preparation of intermediate 2-fluoro-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamides containing a sulfamoyl group in the 5-position via selective acylation of 5-methyl-1,3,4-thiadiazol-2-amine with 5-chlorosulfonyl-2-fluorobenzoyl chloride, followed by sulfonylation of amines.
- Shlenev,Tarasov,Filimonov,Agat’ev,Danilova,Suponitskii, K. Yu.
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p. 1870 - 1877
(2018/02/06)
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- Benzoisothiazolone organo/copper-cocatalyzed redox dehydrative construction of amides and peptides from carboxylic acids using (EtO)3P as the reductant and O2 in air as the terminal oxidant
-
Carboxylic acids and amine/amino acid reactants can be converted to amides and peptides at neutral pH within 5-36 h at 50 °C using catalytic quantities of a redox-active benzoisothiazolone and a copper complex. These catalytic "oxidation-reduction condensation" reactions are carried out open to dry air using O2 as the terminal oxidant and a slight excess of triethyl phosphite as the reductant. Triethyl phosphate is the easily removed byproduct. These simple-to-run catalytic reactions provide practical and economical procedures for the acylative construction of C-N bonds.
- Liebeskind, Lanny S.,Gangireddy, Pavankumar,Lindale, Matthew G.
-
supporting information
p. 6715 - 6718
(2016/06/14)
-
- Manufacturing Development and Genotoxic Impurity Control Strategy of the Hedgehog Pathway Inhibitor Vismodegib
-
The development work toward the robust and efficient manufacturing process to vismodegib, the active pharmaceutical ingredient (API) in Erivedge, is described. The optimization of the four-stage manufacturing process was designed to produce the API with the required critical quality attributes: (1) the selective catalytic hydrogenation reduction of the nitro compound 3 to the corresponding aniline 4 while minimizing the formation of potential genotoxic (mutagenic) impurities; (2) the control of the polymorphic phase and multipoint specification for particle size distribution.
- Angelaud, Remy,Reynolds, Mark,Venkatramani, Cadapakam,Savage, Scott,Trafelet, Huldreich,Landmesser, Thomas,Demel, Peter,Levis, Michael,Ruha, Olivier,Rueckert, Baerbel,Jaeggi, Heinz
-
supporting information
p. 1509 - 1519
(2016/08/30)
-
- Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-aryl Propanamides as Novel Smoothened (Smo) Antagonists
-
A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/-;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.
- Liu, Gang,Xue, Ding,Yang, Jun,Wang, Juan,Liu, Xiaohua,Huang, Wenjing,Li, Jie,Long, Ya-Qiu,Tan, Wenfu,Zhang, Ao
-
p. 11050 - 11068
(2016/12/30)
-
- Regioselective synthesis of 1-substituted indazole-3-carboxylic acids
-
In this article, we study the synthesis of 1-substituted indazole-3-carboxylic acids from 2-halobenzoic acids.
- Veerareddy, Arava,Gogireddy, Surendrareddy,Dubey
-
p. 1311 - 1321
(2015/04/27)
-
- Synthesis and evaluation of novel N-3-benzimidazolephenylbisamide derivatives for antiproliferative and Hedgehog pathway inhibitory activity
-
A series of novel N-3-benzimidazolephenylbisamide derivatives bearing the 4-benzyloxyphenyl moiety were synthesized and evaluated for their antiproliferative activity against MGC803, HT29, MKN45 and SW620 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of the target compounds exhibited higher efficacy against MGC803, HT29 and MKN45 cells, among which compound 7m displayed higher antiproliferative activity than vismodegib. Furthermore, compound 7m manifested better inhibition of the Hedgehog (Hh) signaling pathway in different Hh-related assays and may compete with boron-dipyrromethene (BODIPY)-cyclopamine for binding to the human smoothened (Smo) receptor. In addition, molecular docking studies suggested that compound 7m interacts very closely with the vismodegib docking pose through hydrogen bonds at the taladegib binding site of the Smo receptor.
- Sun, Chiyu,Li, Yangsheng,Shi, Ailong,Zhang, Jingzhou,Li, Yafei,Zhao, Mingming,Zhang, Lijuan,Zheng, Huachuan,Meng, Ying,Ding, Huaiwei,Song, Hongrui
-
supporting information
p. 1137 - 1142
(2015/06/25)
-
- Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
-
The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun. 2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.
- Caraballo, Rémi,Larsson, Mikael,Nilsson, Stefan K.,Ericsson, Madelene,Qian, Weixing,Tran, Nam Phuong Nguyen,Kindahl, Tomas,Svensson, Richard,Saar, Valeria,Artursson, Per,Olivecrona, Gunilla,Enquist, Per-Anders,Elofsson, Mikael
-
p. 191 - 209
(2015/09/15)
-
- N-(3-carbamoylphenly)-1H-pyrazole-5-carboxamide derivatives and the use thereof for controlling animal pests
-
The invention relates to compounds of the general formula (I) in which the radicals A1, A2, A3, A4, L, Q, R1, T and W have the meaning given in the description and to the use of the compounds for controlling animal pests. The invention furthermore relates to processes and intermediates for preparing the compounds of formula (I).
- -
-
Page/Page column 98
(2015/09/28)
-
- NEW PLASMA LIPID LOWERING AGENTS
-
The present invention relates to new plasma lipid lowering compounds and pharmacological compositions,and their use in the prophylaxis, prevention and treatment of hyperlipidemia, including hypertriglyceridemia, hyperlipoproteinemia, and hypercholesterolemia, as well as hyperlipidemia-related diseases.
- -
-
Page/Page column 21; 22; 42
(2015/12/24)
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- Novel N-acyl/aroyl-2-(5-phenyl-2H-tetrazol-2-yl)acetohydrazides: Synthesis and characterization
-
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)
-
- An efficient copper mediated synthetic methodology for benzo[d]isothiazol- 3(2H)-ones and related sulfur-nitrogen heterocycles
-
A copper mediated sulfur-nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones and related sulfur-nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur powder, 25-50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.
- Bhakuni, Bhagat Singh,Balkrishna, Shah Jaimin,Kumar, Amit,Kumar, Sangit
-
supporting information; body text
p. 1354 - 1357
(2012/04/10)
-
- A highly efficient copper-catalyzed method for the synthesis of 2-hydroxybenzamides in water
-
An efficient copper-catalyzed synthetic method for the preparation of 2-hydroxybenzamides is described for the first time from 2-chlorobenzamide substrates using copper iodide/1,10-phenanthroline and a base, potassium hydroxide, in neat water. By using this reaction, a series of 2-hydroxybenzamides with functional groups such as fluoro, chloro, iodo, methoxy, amide, and alcohol have been obtained in 33-96% yield. Other aromatic 2-chloroarylamides such as naphthalene, pyridine, and thiophene are found to be equally compatible to the reaction. It is proposed that the reaction proceed via formation of copper-amide complex, which may facilitate the hydroxylation in water. Overall, the first report on copper-catalyzed hydroxylation reaction in water and first catalytic route for the synthesis of 2-hydroxybenzamides is presented. Simple purification procedure and convenience of employing low-cost reagents in neat water make this method practical and economical for the synthesis of 2-hydroxybenzamides. Georg Thieme Verlag Stuttgart · New York.
- Balkrishna, Shah Jaimin,Kumar, Sangit
-
experimental part
p. 1417 - 1426
(2012/06/30)
-
- Acyl Guanidine Derivatives Modulating The Hedgehog Protein Signaling Pathway
-
The present invention relates to acyl guanidine derivatives modulating the hedgehog protein signaling pathway to be used as drugs, in particular for treating diseases involving a tissue dysfunction associated with a deregulation of the hedgehog protein signaling pathway, as well as to pharmaceutical compositions containing same. The present invention also relates to novel acyl guanidine derivatives as such.
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-
Page/Page column 14
(2012/08/08)
-
- Isonicotinic acid hydrazide derivatives: Synthesis, antimicrobial activity, and QSAR studies
-
A series of isonicotinic acid hydrazide derivatives (1-19) was synthesized and tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis and antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger and the results indicated that the compounds with OH, SCH3, and OCH 3 groups were found to be active against the tested strains. None of the test compounds were active against a broad variety of RNA and DNA viruses at subtoxic concentrations, except 8, that showed some selective anti-reovirus-1 activity. The multi-target QSAR models were found to be effective in predicting the antimicrobial activity of the isoniazid derivatives and indicated the importance of nuclear repulsion energy (Nu.E) in explaining the antimicrobial activity of isoniazid derivatives. The developed QSAR models were validated using the external test set of synthesized derivatives. Springer Science+Business Media, LLC 2011.
- Judge, Vikramjeet,Narasimhan, Balasubramanian,Ahuja, Munish,Sriram, Dharmarajan,Yogeeswari, Perumal,De Clercq, Erik,Pannecouque, Christophe,Balzarini, Jan
-
experimental part
p. 1451 - 1470
(2012/09/22)
-
- Synthesis of (2-chlorophenyl)(phenyl)methanones and 2-(2-chlorophenyl)-1- phenylethanones by Friedel-Crafts acylation of 2-chlorobenzoic acids and 2-(2-chlorophenyl)acetic acids using microwave heating
-
Several 2-(2-chlorophenyl)-1-phenylethanones and (2-chlorophenyl)(phenyl) methanones were prepared by the Friedel-Crafts acylation reaction of 2-(2-chlorophenyl) acetic acids and 2-chlorocarboxylic acids, respectively, in the presence of cyanuric chloride, pyridine, and AlCl3 or FeCl 3 using microwave heating. The yields of the ketones were significantly higher than those obtained using conventional heating. In addition, similar reactions carried out with the less inexpensive and less toxic FeCl3 gave titled ketones in comparable yields. Interestingly, the FeCl3 catalyzed reactions gave pure ketones (no chromatographic purification required), whereas the AlCl3 catalyzed reaction gave impure product that required chromatographic purification.
- Mahdi, Jasia,Ankati, Haribabu,Gregory, Jill,Tenner, Brian,Biehl, Edward R.
-
experimental part
p. 2594 - 2596
(2011/06/21)
-
- Study on the structure-activity relations of pleuromutilin derivatives with an aromatic amide and a thioether group in the C14 side chain
-
Nine novel pleuromutilin derivatives having benzamide substituents have been synthesised permitting structureactivity relations of pleuromutilin derivatives with aromatic amide and thioether groups in the C14 side chain to be studied. The results showed that the heterocyclic carboxamide group was necessary to enhance bio-activities.
- Xu, Ke-Ping,Zhang, Yuan-Yuan,Luo, Juan,Chen, Shan-Li,Wang, Yu-Liang
-
experimental part
p. 354 - 357
(2010/10/21)
-
- Mechanistic insights into a copper-disulfide interaction in oxidation of imines by disulfides
-
The concept of using disulfides as an oxidant for Cu(i) is introduced as part of a Cu-catalyzed process leading to the formation of benzothiazole from an iminodisulfide under an inert atmosphere.
- Srogl, Jiri,Hyvl, Jakub,Revesz, Agnes,Schroeder, Detlef
-
supporting information; experimental part
p. 3463 - 3465
(2009/12/26)
-
- Hansch analysis of substituted benzoic acid benzylidene/furan-2-yl-methylene hydrazides as antimicrobial agents
-
A series of substituted hydrazide derivatives have been synthesized and screened for their in vitro antimicrobial activities against five representative microorganisms. The results of antimicrobial study indicated that the presence of electron withdrawing groups on the benzoic acid moiety improved antimicrobial activity. Further, the presence of heterocyclic ring furan does not improve the antimicrobial activity of substituted hydrazides. To understand the relationship between physicochemical parameters and antimicrobial activity of substituted hydrazide derivatives, QSAR investigation was performed by the development of one-target and multi-target models. The multi-target model was found to be effective in describing the antimicrobial activity of substituted hydrazides in comparison to the one-target models. Further, it indicated the importance of the topological parameter, valence third order molecular connectivity index (3χv) and the electronic parameter, energy of highest occupied molecular orbital (HOMO) in describing the antimicrobial activity of substituted hydrazides.
- Kumar, Pradeep,Narasimhan, Balasubramanian,Sharma, Deepika,Judge, Vikramjeet,Narang, Rakesh
-
experimental part
p. 1853 - 1863
(2009/09/30)
-
- NPY ANTAGONISTS, PREPARATION AND USES
-
The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.
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Page/Page column 86
(2009/09/28)
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- Synthesis and biological evaluation of SANT-2 and analogues as inhibitors of the hedgehog signaling pathway
-
Hedgehog (Hh) signaling plays an important role in cell signaling of embryonic development and adult tissue homeostasis. In vertebrates, the hh gene encodes three different unique proteins: sonic hedgehog (Shh), desert hedgehog (Dhh) and indian hedgehog (Ihh). Disruption of the Hh signaling pathway leads to severe disorders in the development of vertebrates whereas aberrant activation of the Hh pathway has been associated with several malignancies including Gorlin syndrome (a disorder predisposing to basal cell carcinoma, medulloblastoma and rhabdomyosarcoma), prostate, pancreatic and breast cancers. In vivo evidence suggests the antagonism of excessive Hh signaling provides a route to unique mechanism-based anti-cancer therapies. Recently the small molecule SANT-2 was identified as a potent antagonist of Hh-signaling pathway. Here, we describe the synthesis, SAR studies as well as biological evaluation of SANT-2 and its analogues. Fifteen SANT-2 derivatives were synthesized and analyzed for their interference with the expression of the Hh target gene Gli1 in a reporter gene assay. By comparison of structure and activity important molecular descriptors for Gli inhibition could be identified. Furthermore we identified derivative TC-132 that was slightly more potent than the parent compound SANT-2. Selected compounds were tested for Hh related teratogenic effects in the small teleost model medaka. Albeit Gli expression has indicated a 16-fold higher Hh-inhibiting activity than observed for the plant alkaloid cyclopamine, none of the tested compounds were able to induce the cyclopamine-specific phenotype in the medaka assay.
- Buettner, Anita,Seifert, Katrin,Cottin, Thomas,Sarli, Vasiliki,Tzagkaroulaki, Lito,Scholz, Stefan,Giannis, Athanassios
-
experimental part
p. 4943 - 4954
(2009/12/24)
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- 2- [ (2-SUBSTITUTED) -IND0LIZIN-3-YL] -2-OXO-ACETAMIDE DERIVATIVES AS ANTIFUNGAL AGENTS
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The invention provides compounds of formula (I), and pharmaceutically acceptable salts thereof wherein: Rl, R2, R3, R4, R5, R6, R7, X and X1 are as defined herein. These compounds are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 125
(2008/12/05)
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- BENZAMIDE DERIVATIVES AS EP4 RECEPTOR AGONISTS
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A compound of formula (I) or a pharmaceutically acceptable derivative thereof, wherein, R1, R2, R3, R4, R5, m, n and X are as defined in the specification; a process for preparing such compounds; a pharmaceutical composition comprising such compounds; and the use of such compounds in medicine.
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Page/Page column 50-51
(2008/12/06)
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- Thioimides: New reagents for effective synthesis of thiolesters from carboxylic acids
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(Chemical Equation Presented) Thioimides and carboxylic acids are used as the precursors for the convenient synthesis of thiolesters in the phosphine mediated process. Cyclic and acyclic thioimides show equal efficiency, furnishing the desired thiolesters in good to excellent yields. The general, highly efficient transformation tolerates various functional groups and the resulting thiolesters are obtained in high purity after a simple separation. The reaction scope has been demonstrated on the preparation of several highly functionalized target molecules.
- Henke, Adam,Srogl, Jiri
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p. 7783 - 7784
(2008/12/22)
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- Benzoylurea derivatives as a novel class of antimitotic agents: Synthesis, anticancer activity, and structure-activity relationships
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Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC50 values between 0.01 and 0.30 μM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.
- Song, Dan-Qing,Wang, Yan,Wu, Lian-Zong,Yang, Peng,Wang, Yue-Ming,Gao, Li-Mei,Li, Yan,Qu, Jing-Rong,Wang, Yong-Hong,Li, Ying-Hong,Du, Na-Na,Han, Yan-Xing,Zhang, Zhi-Ping,Jiang, Jian-Dong
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experimental part
p. 3094 - 3103
(2009/04/06)
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- Synthesis of bis(arylcarbonylamino-1H-benzimidazol-5-yl) ethers
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A procedure has been developed for the synthesis of bis(arylcarbonylamino- 1H-benzimidazol-5-yl) ethers by reaction of the corresponding substituted benzoyl chloride with sodium cyanamide, followed by treatment of the resulting N-cyanobenzamide with 4-(3,4-diaminophenoxy)benzene-1,2-diamine in acid medium. Nauka/Interperiodica 2006.
- Pilyugin,Sapozhnikov,Chikisheva,Kiseleva,Vorob'eva,Klimakova,Sapozhnikova,Kuznetsova
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p. 1327 - 1330
(2008/02/04)
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- Methods for producing amino substituted chromanes and intermediates therefor
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Disclosed are process steps and processes for producing chromane compounds, preferably 2-(6-amino-chroman-2yl) acetic acid esters which are intermediates for producing platelet aggregation inhibitors and/or are themselves potent platelet aggregation inhibitors.
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- Tricyclic compounds with NOS activity
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The present invention provides novel tricyclic compounds, compositions comprising these compounds and methods of using these compounds as neuroprotectants. In particular, the compounds of the invention are useful for treating stroke.
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Page/Page column 18
(2008/06/13)
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- Aryl triazines as LPAAT-SS inhibitors and uses thereof
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The invention relates to aryl triazines and uses thereof, including to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity and/or proliferation of cells such as tumor cells.
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- Benzoxazole LPAAT-B inhibitors and uses thereof
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The invention relates to benzoxazoles and the use thereof to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity. The invention further relates to methods of treating cancer using said benzoxazoles. The invention also relates to methods for screening for LPAAT-β activity.
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- Synthesis of racemic 1,2,3,4-tetrahydroisoquinolines and their resolution
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1-Aniline-substituted 3,4-dihydroisoquinolines were obtained in various ways using the Bischler-Napieralski reaction. The effect of the protecting group at the aniline nitrogen atom on the course of the reaction has been studied and it was found that the N-phthalyl group was stable under the cyclization conditions. The dihydroisoquinolines were reduced to the racemic 1,2,3,4-tetrahydroisoquinolines which were resolved by crystallization of the diastereomeric tartrates. Two examples of 1,2,3, 4-tetrahydroisoquinolines were obtained in optically pure form (>99% ee).
- Suna,Trapencieris
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p. 287 - 300
(2007/10/03)
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- Synthesis of nitrogen and sulfur analogues of the seco-CI alkylating agent
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Two complementary syntheses of amino seco-CI (CI = 1a,2,3,5-tetrahydro-1H-cycloprop[1,2-c]indol-5-one) alkylating agents starting from isomeric chloronitrobenzoic acids are reported. Further reactions of these compounds, including diazotisation to phenol and thiophenol derivatives, and alkylation and acylation reactions relevant to the preparation of pro-drug forms are also described.
- Tercel, Moana,Denny, William A.
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p. 509 - 519
(2007/10/03)
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- Substituted N-Cyanomethyl-2-halo-N-methylarenecarboxamides as Precursors of 1,4-Benzothiazepines
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2-Halogeno substituted N-cyanomethyl-N-methylbenzamides 1a-1i were investigated in a correlation analysis by ir spectroscopy to determine the conformational behavior. Compound 1h gives 4-methyl-2-methylthio-8-nitro-5-oxo-4,5-dihydro-1,4-benzothiazepine-3- carbonitrile 3 by dithiocarboxylation procedure whereas 1b was not able to react to heterocyclic seven-membered ring system.
- Doelling, Wolfgang,Perjessy, Alexander,Schaller, Ingrid,Kolbe, Alfred
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p. 225 - 229
(2007/10/03)
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- A facile synthesis of substituted 1,4-benzothiazepin-5(4H)-ones and pyrido[3,2-f][1,4]thiazepin-5(4H)-ones - crystal and molecular structure of 2-ethylthio-4-methyl-5(4H)-oxopyrido[3,2-f][1,4]thiazepine-3-carbonitrile
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A new synthesis of pyrido[3,2-f][1,4]thiazepine derivatives 3 starting with 2-chloronicotinic acid (1), methylaminoacetonitrile hydrochloride and carbon disulfide is described. As proved by a crystal structure determination, a boat conformation with approximated mirror symmetry can be assigned to the 1,4-thiazepine ring in 3b. 2-Chloro-N-cyanomethyl-N-methyl-5-nitrobenzamide (5) reacts with carbon disulfide in presence of a strong base in DMF or DMSO depending on the temperature to either the benzothiopyran compound 6 or by intramolecular aromatic nucleophilic substitution to a seven-membered ring system as thiolate anion which can be alkylated to give the 1,4-benzothiazepine derivative 7, or to an open-chain amido ketene dithioacetal 8.
- Dolling, Wolfgang,Biedermann, Matthias,Hartung, Helmut
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p. 1237 - 1242
(2007/10/03)
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- Synthesis and antitumor activity of novel benzophenone derivatives
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Novel benzophenone derivatives were synthesized and screened for cytotoxic and antitumor activity. Friedel-Crafts condensation was employed to construct the benzophenone skeleton. Among the compounds synthesized, morpholino and thiomorpholino benzophenones 3a-d exhibited potent cytotoxic activity against P388 murine leukemia and PC-6 human lung carcinoma cells in vitro, and compounds 3a, 3c, and 3j, when administered intraperitoneally, showed significant antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice.
- Kumazawa, Eiji,Hirotani, Kenji,Burford, S. Clifford,Kawagoe, Keiichi,Miwa, Tamotsu,Mitsui, Ikuo,Ejima, Akio
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p. 1470 - 1474
(2007/10/03)
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- Utility of Complementary Molecular Reactivity and Molecular Recognition (CMR/R) Technology and Polymer-Supported Reagents in the Solution-Phase Synthesis of Heterocyclic Carboxamides
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The use of our recently reported chemical library purification strategy in the development of a herbicidal lead, N-(3-benzoylphenyl)-3-(1,1-dimethylethyl)-1-methyl-1H-pyrazole-5-carboxamide (3), is described. The approach applying fundamental properties of complementary molecular reactivity and molecular recognition (CMR/R) as the basis for a general purification strategy was utilized. Polymeric reagents were used in the synthesis to generate reactive species involved in product formation, and complementary molecular reactivity/molecular recognition polymer 8 (CMR/R polymer 8) was used in the solution-phase syntheses of building blocks, primary libraries, and lead refinement libraries. An extension of the CMR/R methodology was applied, utilizing a sequestration enabling reagent (SER), transforming a reactant into an electrophilic species sequestrable by CMR/R polymer 8. This library purification strategy enabled rapid lead generation and lead refinement to afford herbicide 27o. The CMR/R solid-phase purification technique enabled a simple, general, and powerful protocol, eliminating the usual tedious and time-consuming methods required for solution-phase product purification. The result was the synthesis of hundreds of compounds, prepared in a relatively short time, leading to a compound with a 4-fold improvement in herbicidal activity over the initial lead.
- Parlow, John J.,Mischke, Deborah A.,Woodard, Scott S.
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p. 5908 - 5919
(2007/10/03)
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