cas 1878-49-5, (2-Methylphenoxy)acetic acid

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Optimization of NAMPT activators to achieve in vivo neuroprotective efficacy
NAMPT is the rate-limiting enzyme in the NAD salvage pathway, which makes it an attractive target for the treatment of many diseases associated with NAD exhaustion such as neurodegenerative diseases. Herein, we present the systematic optimization of NAT, an initial hit of NAMPT activator discovered by us through high-throughput screening, based on the co-crystal structure of the NAMPT-NAT complex. Over 80 NAT derivatives have been designed and synthesized, among which compound 72 showed notably improved potency as NAMPT activator and effectively protected cultured cells from FK866-mediated toxicity. Moreover, compound 72 exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) without any overt toxicity, which renders it a promising candidate for the development of novel neuroprotective agents.
Hua, Lan,Liu, Minghui,Liu, Yang,Lu, Haigen,Ma, Weinan,Tang, Yefeng,Wang, Gelin,Wang, Leibo,Wu, Chou,Xi, Shuang,Yao, Hong,Zhang, Ruoxi,Zu, Yumeng
(2022/04/07)

PEPTIDES, COMPOUNDS, COMPOSITIONS AND METHODS FOR INHIBITING SOX9 DIMERIZATION
The present application provides SOX9 dimerization inhibitor compounds, compositions, and methods of use thereof. In certain aspects, the SOX9 dimerization inhibitor is a peptide comprising a portion of the SOX9 dimerization motif and a TAT protein to support cell entry which is c-terminal to the SOX9 dimerization motif as set forth in SEQ ID NO:3. In other aspects, the SOX9 dimerization inhibitor is a compound of the general formula I (The applicant is kindly asked to please insert chemical structure here) where one A is H and the other is: (please insert second chemical structure here), and the remaining substituents are as defined in the application.
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Paragraph 0097; 00110-00111; 00150-00152

(2021/05/29)

Method for preparing 2-methyl-4-chlorophenoxyacetic acid through catalytic chlorination of 2-methylphenoxyacetic acid
The invention relates to a preparation method of 2-methyl-4-chlorophenoxyacetic acid, in particular to a method for preparing 2-methyl-4-chlorophenoxyacetic acid through catalytic chlorination of 2-methylphenoxyacetic acid. The method comprises the following steps: by taking o-methylphenoxyacetic acid (MPA) as a raw material, performing a reaction in the presence of chlorine by virtue of a catalyst, and filtering, so as to obtain the 2-methyl-4-chlorophenoxyacetic acid (MCPA), wherein the catalyst is imidazole ionic liquid. By means of the catalyst, the reaction activity is relatively high, the o-methyl phenoxyacetic acid is subjected to catalytic chlorination reaction, and the 2-methyl-4-chlorophenoxyacetic acid is prepared at a high yield; besides, compared with existing literature reports, the reaction system is simple and convenient to operate, no wastewater is generated in the chlorination step, a high-quality product can be obtained, and large-scale production is facilitated.
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Paragraph 0041; 0044-0045

(2021/03/13)

Shape Similarity by Fractal Dimensionality: An Application in the de novo Design of (?)-Englerin A Mimetics
Molecular shape and pharmacological function are interconnected. To capture shape, the fractal dimensionality concept was employed, providing a natural similarity measure for the virtual screening of de novo generated small molecules mimicking the structurally complex natural product (?)-englerin A. Two of the top-ranking designs were synthesized and tested for their ability to modulate transient receptor potential (TRP) cation channels which are cellular targets of (?)-englerin A. Intracellular calcium assays and electrophysiological whole-cell measurements of TRPC4 and TRPM8 channels revealed potent inhibitory effects of one of the computer-generated compounds. Four derivatives of this identified hit compound had comparable effects on TRPC4 and TRPM8. The results of this study corroborate the use of fractal dimensionality as an innovative shape-based molecular representation for molecular scaffold-hopping.
Bauer, Christoph,Byrne, Ryan,Friedrich, Lukas,Gudermann, Thomas,Mederos y Schnitzler, Michael,Schneider, Gisbert,Singh, Inderjeet,Storch, Ursula,Treder, Aaron
supporting information

(2020/03/24)

Design and Synthesis of Novel 4-Hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one Derivatives for Use as Herbicides and Evaluation of Their Mode of Action
In order to develop a novel herbicide containing the β-triketone motif, a series of 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one derivatives were designed and synthesized. The bioassay results showed that compound II15 had good pre-emergent herbicidal activity even at a dosage of 187.5 g ha-1. Moreover, compound II15 showed a broader spectrum of weed control when compared with a commercial herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), and displayed good crop safety to Triticum aestivum L. and Zea mays Linn. when applied at 375 g ha-1 under pre-emergence conditions, which indicated its great potential as a herbicide. More importantly, studying the molecular mode of action of compound II15 revealed that the novel triketone structure is a proherbicide of its corresponding phenoxyacetic acid auxin herbicide, which has a herbicidal mechanism similar to that of 2,4-D. The present work indicates that the 4-hydroxyl-3-(2-phenoxyacetyl)-pyran-2-one motif may be a potential lead structure for further development of novel auxin-type herbicides.
Lei, Kang,Li, Pan,Yang, Xue-Fang,Wang, Shi-Ben,Wang, Xue-Kun,Hua, Xue-Wen,Sun, Bin,Ji, Lu-Sha,Xu, Xiao-Hua
p. 10489 - 10497
(2019/10/02)

Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones
We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L?1 d?1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.
Wang, Zexu,Wu, Xiaofan,Li, Zhining,Huang, Zedu,Chen, Fener
supporting information
p. 3575 - 3580
(2019/04/14)

PRMT5 INHIBITORS AND USES THEREOF
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
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Paragraph 0260-0261

(2019/04/05)

2-methyl-4-chlorophenoxyacetic acid preparation method
The invention provides a 2-methyl-4-chlorophenoxyacetic acid preparation method, which comprises: carrying out a condensation reaction on sodium o-cresolate and sodium chloroacetate under the catalysis of a trimethylamine catalyst to obtain 2-methyl sodium phenoxyacetate, acidifying, and chlorinating to obtain 2-methyl-4-chlorophenoxyacetic acid. According to the present invention, under the catalysis of the trimethylamine catalyst, sodium o-cresolate and sodium chloroacetate can be subjected to the condensation reaction in the near-neutral environment with the temperature of lower than 70 DEGC, such that the main side reaction for hydrolyzing sodium chloroacetate into sodium glycolate is greatly reduced, the produced wastewater contains less o-methylphenol and glycolic acid (or sodium glycolate) so as to easily meet the nationally acceptable emission standards at a low treatment cost, the resource utilization of the waste acid solution can be achieved, the cost of the raw materials and the three-waste treatment cost are reduced, the purity of 2-methyl-4-chlorophenoxyacetic acid is higher than 95%, and the total yield is higher than 93%.
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Page/Page column 7-13

(2019/08/01)

Method for synthesizing phenoxyacetic acid derivatives
The invention relates to a method for synthesizing phenoxyacetic acid derivatives. The method comprises the steps of mixing a salt compound of phenol or cresol and a salt compound of chloroacetic acid, putting the mixture into a solvent for heating reaction, and performing acidification by an inorganic acid to obtain phenoxyacetic acid; and then, dissolving the phenoxyacetic acid in a solvent, adding a catalyst, introducing chlorine gas for heating chlorination reaction, and performing cooling crystallization to obtain a chlorine-substituted phenoxyacetic acid (or methylphenoxyacetic acid) derivative. Compared with the prior art, during the reaction process, the solvent of the reaction system and wastewater are recovered for recycled, so that the method satisfies production balance and cyclic utilization of a closed system, the yield is more than 95%, the product content is more than 98%, the utilization rate of the recycled solvent is greater than 95%, and wastewater emission is reduced by 95% or more in the entire production process.
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Paragraph 0029-0031

(2018/04/21)

The Novel 4-Phenyl-2-Phenoxyacetamide Thiazoles modulates the tumor hypoxia leading to the crackdown of neoangiogenesis and evoking the cell death
Tumor microenvironment is a complex multistep event which involves several hallmarks that transform the normal cell into cancerous cell. Designing the novel antagonistic molecule to reverse the tumor microenvironment with specific target is essential in modern biological studies. The novel 4-phenyl-2-phenoxyacetamide thiazole analogues 8a-ab were synthesized in multistep process, then screened and assessed for cytotoxic and anti-proliferative effects in vitro against multiple cancer cells of different origin such as MCF-7, A549, EAC and DLA cells which revealed that compound 8f with fluoro and methyl substitute has potential cytotoxic efficacy with an average IC50 value of ? 13 μM. The mechanism of cytotoxicity assessed for anti-tumor studies both in ascites and solid tumor models in-vivo inferred the regressed tumor activity. This is due to changes in the cause of tumor microenvironment with crackdown of neovascularization and evoking apoptosis process as assessed by CAM, corneal vascularization and apoptotic hallmarks in 8f treated cells. The molecular gene studies inferred involvement of HIF-1upregulation and stabilization of p53 which are interlinked in signaling as conferred by immunoblot analysis.
Mohammed, Yasser Hussein Eissa,Malojirao, Vikas H.,Thirusangu, Prabhu,Al-Ghorbani, Mohammed,Prabhakar,Khanum, Shaukath Ara
p. 1826 - 1839
(2017/11/16)

Synthetic method of 2-methyl-4-chlorophenoxyacetic acid
The invention discloses a synthetic method of 2-methyl-4-chlorophenoxyacetic acid, and relates to the technical field of organic synthesis. The target product 2-methyl-4-chlorophenoxyacetic acid is prepared by taking o-methylphenol as a raw material, reacting with sodium chloroacetate udner the effect of sodium bicarbonate; neutralizing by hydrochloric acid to obtain a midbody 2-methyl phenoxyacetic acid; finally, chloridizing the midbody 2-methyl phenoxyacetic acid by chlorine. The method applies sodium bicarbonate to replace sodium hydroxide to carry out neutralization, the neutralization reaction is small in heat release and few in side product; the method is good for improving product content and yield; besides, the chorine is applied to chloridize, and methylbenzene is used as the solvent; the generated acid is used as the neutralizing acid of the next batch, thus the massive phenolic wastewater is reduced, and it can meet the requirement of modern green pesticide; carbon dioxideis discharged from the neutralization reaction, the reaction heat is reduced, and the energy consumption is reduced. Compared with an original technique, the reaction technique has obvious advantagesof high yield, few wastes and low energy consumption.
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Paragraph 0018; 0021; 0030; 0032

(2018/03/26)

Synthesis method of 2-methyl-4-chlorophenoxyacetic acid
The invention discloses a synthesis method of 2-methyl-4-chlorophenoxyacetic acid, and relates to the technical field of organic synthesis. The synthesis method comprises the following steps that methyl phenoxyacetic acid and methyl ethyl carbonate are added into a reaction kettle, chlorine is introduced for chlorination, and after washing, cooling crystallization, suction filtration and drying are conducted, the target product is obtained. According to the synthesis method of the 2-methyl-4-chlorophenoxyacetic acid, the methyl ethyl carbonate is adopted for replacing dichloroethane, so that by-products are few, and the synthesis method of the 2-methyl-4-chlorophenoxyacetic acid is beneficial for improving the content and the yield of the product; a large amount of waste acid is avoided, and the solvent (methyl ethyl carbonate) is environmentally friendly and non-toxic, and meets the requirements of modern green pesticides; compared with an original technology, a reaction technology has the obvious advantages of high yield, little three-waste and low energy consumption.
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Paragraph 0018; 0020; 0021; 0025-0029; 0032; 0033; 0037-0038

(2018/12/13)

Isoflavone amide derivatives, their preparation method and medical use
The invention belongs to the field of medicinal chemistry, and relates to derivatives of isoflavones amides, as well as a preparation method and medical application of derivatives, in particular to the derivatives of the isoflavones amides with the general formula of (I) shown as the specification, the preparation method and the medical application of the derivatives, particularly the application of the derivatives of the isoflavones amides serving as medicaments for preventing or treating hyperlipemia, adiposis or type-II diabetes.
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Paragraph 0077

(2017/08/31)

The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases
Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.
Eissa Mohammed, Yasser Hussein,Thirusangu, Prabhu,Zabiulla,Vigneshwaran,B.T, Prabhakar,Khanum, Shaukath Ara
p. 375 - 386
(2017/09/02)

Formononetin derivatives and preparation methods and medical application thereof
The invention relates to the field of pharmaceutical chemistry, and relates to formononetin derivatives and preparation methods and medical application thereof, in particular to formononetin derivatives with the general formula as shown in (I), preparation methods thereof, pharmaceutical compositions containing the compounds and medical application of the derivatives and the pharmaceutical compositions, particularly, application of the derivatives and the pharmaceutical compositions serving as drugs for preventing or treating hyperlipidaemia or obesity or type-II diabetes. Please see the formula in the description.
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Paragraph 0069; 0070; 0071; 0072; 0073; 0074

(2017/04/29)

Synthesis and biological evaluation of aryloxyacetamide derivatives as neuroprotective agents
A series of new aryloxyacetamide derivatives 10a-s and 14a-m are designed and synthesized. Their protective activities against the glutamate-induced cell death were investigated in differentiated rat pheochromocytoma cells (PC12 cells). Most compounds exhibited neuroprotective effects, especially for 10m, 10r, 14b and 14c, which showed potential protection of PC12 cells at three doses (0.1, 1.0, 10 μM). MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 10m, 10r, 14b and 14c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke. Basic structure-activity relationships are also presented.
Zhong, Yan,Xu, Yi,Zhang, Ai-Xia,Li, Xiao-Feng,Xu, Zhao-Ying,Li, Ping,Wu, Bin
p. 2526 - 2530
(2016/07/07)

An Efficient One-Pot Synthesis of 2-(Aryloxyacetyl)cyclohexane-1,3-diones as Herbicidal 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is an important target for new bleaching herbicides discovery. As a continuous work to discover novel crop selective HPPD inhibitor, a series of 2-(aryloxyacetyl)cyclohexane-1,3-diones were rationally designed and synthesized by an efficient one-pot procedure using N,N′-carbonyldiimidazole (CDI), triethylamine, and acetone cyanohydrin in CH2Cl2. A total of 58 triketone compounds were synthesized in good to excellent yields. Some of the triketones displayed potent in vitro Arabidopsis thaliana HPPD (AtHPPD) inhibitory activity. 2-(2-((1-Bromonaphthalen-2-yl)oxy)acetyl)-3-hydroxycyclohex-2-en-1-one, II-13, displayed high, broad-spectrum, and postemergent herbicidal activity at the dosage of 37.5-150 g ai/ha, nearly as potent as mesotrione against some weeds. Furthermore, II-13 showed good crop safety against maize and canola at the rate of 150 g ai/ha, indicating that II-13 might have potential as a herbicide for weed control in maize and canola fields. II-13 is the first HPPD inhibitor showing good crop safety toward canola.
Wang, Da-Wei,Lin, Hong-Yan,He, Bo,Wu, Feng-Xu,Chen, Tao,Chen, Qiong,Yang, Wen-Chao,Yang, Guang-Fu
p. 8986 - 8993
(2016/12/09)

Degradation of organochlorinated pollutants in water by catalytic hydrodechlorination and photocatalysis
The degradation of chlorinated herbicides (MCPA and 2,4-D) and 4-chlorophenol (4-CP) by photocatalytic oxidation (PCO) and the combination of catalytic hydrodechlorination (HDC) and photocatalysis, at ambient conditions, has been studied. Commercial TiO2 (P25) and Pd/Al2O3 catalysts were used for PCO and HDC, respectively. MCPA and 2,4-D were transformed upon photo-oxidation to intermediate products and almost total mineralization was achieved. However, in the case of 4-CP, a conversion of only 82% of chloride formation and 87% TOC were obtained. In spite of the fact that the HDC reaction resulted in a total dechlorination of organochlorinated pollutants combined with an important decrease of the effluent ecotoxicity, the percentage of mineralization obtained in the combined process (HDC-PCO) was slightly lower than in the PCO treatment. Thus, the HDC-PCO process is not justified versus a single PCO treatment.
Diaz, Elena,Cebrian, Marina,Bahamonde, Ana,Faraldos, Marisol,Mohedano, Angel F.,Casas, Jose A.,Rodriguez, Juan J.
p. 168 - 174
(2016/03/25)

Finding new elicitors that induce resistance in rice to the white-backed planthopper Sogatella furcifera
Herein we report a new way to identify chemical elicitors that induce resistance in rice to herbivores. Using this method, by quantifying the induction of chemicals for GUS activity in a specific screening system that we established previously, 5 candidate elicitors were selected from the 29 designed and synthesized phenoxyalkanoic acid derivatives. Bioassays confirmed that these candidate elicitors could induce plant defense and then repel feeding of white-backed planthopper Sogatella furcifera.
He, Xingrui,Yu, Zhaonan,Jiang, Shaojie,Zhang, Peizhi,Shang, Zhicai,Lou, Yonggen,Wu, Jun
supporting information
p. 5601 - 5603
(2015/11/17)

Synthesis and biological evaluation of isoflavone amide derivatives with antihyperlipidemic and preadipocyte antiproliferative activities
A series of isoflavone amides were designed with isoflavone in place of the scaffold of 2-arylbenzoxazole as cholesterol ester transfer protein (CETP) inhibitors. Twelve new compounds were synthesized, and their inhibitory activities of CETP and preadipocyte proliferation were assayed. The hypolipidemic potency of the most effective compound HY-2c was further tested in vivo by hamster. The results indicate that HY-2c exhibited favorable antihyperlipidemic and preadipocyte antiproliferative activities.
Wang, Wenbin,He, Yi,Xu, Pei,You, Qidong,Xiao, Hong,Xiang, Hua
p. 4428 - 4433
(2015/08/03)

Deactivation of a Pd/AC catalyst in the hydrodechlorination of chlorinated herbicides
This work analyses the stability of a palladium on activated carbon (Pd/AC) catalyst in the ambient-like conditions hydrodechlorination (HDC) of the organochlorinated herbicides 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2,4-dichlorophenoxyacetic acid (2,4-D) as well as 2,4-dichlorophenol (2,4-DCP), a precursor in the synthesis of the second. Continuous long term experiments (100h time on stream) were performed at mild operating conditions (30°C, 1 atm). The composition of the reaction effluents was analyzed and their ecotoxicity (Microtox) measured. In all cases, a significant decrease of ecotoxicity was observed due to the high dechlorination achieved. The Pd/AC catalyst maintained a constant activity along the HDC of 2,4-DCP, while it suffered an important deactivation in the HDC of 2,4-D and MCPA. From characterization of the fresh and used catalyst the adsorption/deposition of reaction byproducts on the active sites can be recognized as the main cause of deactivation. The use of activated carbon as support reduces the negative effect that the released chloride ions usually provoke on other HDC catalysts.
Diaz,Mohedano,Casas,Calvo,Gilarranz,Rodriguez
p. 86 - 91
(2015/03/14)

Deactivation of a Pd/AC catalyst in the hydrodechlorination of chlorinated herbicides
This work analyses the stability of a palladium on activated carbon (Pd/AC) catalyst in the ambient-like conditions hydrodechlorination (HDC) of the organochlorinated herbicides 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2,4-dichlorophenoxyacetic acid (2,4-D) as well as 2,4-dichlorophenol (2,4-DCP), a precursor in the synthesis of the second. Continuous long term experiments (100 h time on stream) were performed at mild operating conditions (30 °C, 1 atm). The composition of the reaction effluents was analyzed and their ecotoxicity (Microtox) measured. In all cases, a significant decrease of ecotoxicity was observed due to the high dechlorination achieved. The Pd/AC catalyst maintained a constant activity along the HDC of 2,4-DCP, while it suffered an important deactivation in the HDC of 2,4-D and MCPA. From characterization of the fresh and used catalyst the adsorption/deposition of reaction byproducts on the active sites can be recognized as the main cause of deactivation. The use of activated carbon as support reduces the negative effect that the released chloride ions usually provoke on other HDC catalysts.
Diaz,Mohedano,Casas,Calvo,Gilarranz,Rodriguez
p. 86 - 91
(2015/02/19)

Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA
Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods.
Joshi, Shrinivas D.,More, Uttam A.,Koli, Deepshikha,Kulkarni, Manoj S.,Nadagouda, Mallikarjuna N.,Aminabhavi, Tejraj M.
p. 151 - 167
(2015/03/30)

PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
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Paragraph 00272

(2014/07/08)

Copper(II)-catalyzed hydroxylation of aryl halides using glycolic acid as a ligand
Copper(II)-catalyzed hydroxylation of aryl halides has been developed to afford functionalized phenols. The protocol utilizes the reagent combination of Cu(OH)2, glycolic acid, and NaOH in aqueous DMSO, all of which are cheap, readily available, and easily removable after the reaction. A broad range of aryl iodides and activated aryl bromides were transformed into the corresponding phenols in excellent yields. Moreover, it has been shown that C-O(alkyl)-coupled product, instead of phenol, can be predominantly formed under similar reaction conditions.
Xiao, Yan,Xu, Yongnan,Cheon, Hwan-Sung,Chae, Junghyun
p. 5804 - 5809
(2013/07/25)

Synthesis and biological activity of 2-Aryloxyacetylamino-2-Deoxy-D- Glucoses
D-Glucosamine possesses extensive bioactivities including antibacterial, insecticidal and plant growth-regulating activities. A series of 2-aryloxyacetylamino-2-deoxy-D-glucoses have been synthesized by acylation of D-glucosamine with aryloxyacetyl chlorides and their plant growth-regulating activities were tested. The results show that these compounds bearing chlorine atom at para position of benzene ring have notable inhibiting activities against cotyledon rootage of cucumber which are comparable with that of 2,4-dichlorophenoxyacetic acid.
Han, Liang,Zhu, Qiong-Yan,Jia, Jian-Hong,Li, Yu-Jin,Gao, Jian-Rong
experimental part
p. 1223 - 1226
(2012/09/07)

Electron-transfer-induced reductive cleavage of chlorinated aryloxyalkanoic acids
We investigated the degradation of chlorinated herbicides, with an aryloxyalkanoic acid skeleton, under reductive electron transfer reaction conditions. Although Li and Na metals proved useless, activated forms of these metals, either their soluble naphthalene radical anions or 1,2-diarylethane dianions, promoted the degradation of the starting materials to various extents. Indeed, lithium naphthalenide promoted both extensive dehalogenation and dealkylation of chlorinated aryloxyalkanoic acids, with formation of the corresponding phenols as the main reaction products. In contrast, the employment of 1,2-diphenyl-1,2-disodioethane as a reducing agent led, in most examples, to the chemoselective recovery of the corresponding dechlorinated acids.
Azzena, Ugo,Pittalis, Mario
experimental part
p. 3360 - 3362
(2011/06/11)

Aza-Michael addition of acrylonitrile with 2-aryloxymethylbenzimidazole derivatives under microwave irradiation
A simple, rapid, and highly efficient method has been developed for the aza-Michael addition of acrylonitrile to 2-aryl-oxymethylbenzimidazole derivatives in the presence of anhydrous potassium carbonate under microwave irradiation. A series novel of 1-cyanoethyl-2-aryloxymethylbenzimidazole derivatives have been prepared and characterised by 1H NMR, 13C NMR, IR spectra and elemental analysis.
Wei, Tai-Bao,Hua, Mao-Tang,Shi, Hai-Xiong,Liu, Yong,Zhang, You-Ming
scheme or table
p. 452 - 454
(2010/12/24)

2-Arylbenzoxazoles as CETP inhibitors: Substitution and modification of the α-alkoxyamide moiety
The development of a series of 2-arylbenzoxazole α-alkoxyamide and β-alkoxyamine inhibitors of cholesteryl ester transfer protein (CETP) is described. Highly fluorinated α-alkoxyamides proved to be potent inhibitors of CETP in vitro, and the highly fluorinated 2-arylbenzoxazole β-alkoxyamine 4 showed a desirable combination of in vitro potency (IC50 = 151 nM) and oral bioavailability in the mouse.
Hunt, Julianne A.,Gonzalez, Silvia,Kallashi, Florida,Hammond, Milton L.,Pivnichny, James V.,Tong, Xinchun,Xu, Suoyu S.,Anderson, Matt S.,Chen, Ying,Eveland, Suzanne S.,Guo, Qiu,Hyland, Sheryl A.,Milot, Denise P.,Sparrow, Carl P.,Wright, Samuel D.,Sinclair, Peter J.
scheme or table
p. 1019 - 1022
(2010/06/14)

Synthesis and biological evaluation of some novel 2-mercaptobenzothiazoles carrying 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties
Several 2-mercaptobenzothiazole derivatives containing 1,3,4-oxadiazoles, 1,2,4-triazoles and 1,3,4-thiadiazoles at the second position were synthesized. Some of these synthesized compounds were evaluated for their in vivo analgesic, anti-inflammatory, acute toxicity and ulcerogenic actions. Some of the tested compounds showed significant analgesic and anti-inflammatory activities. Two of the compounds showed significant gastrointestinal protection compared to the standard drug diclofenac sodium. The compounds were also tested for their in vitro antimicrobial activity with most displaying selective activity against the Gram-negative bacteria Pseudomonas aeruginosa. In the present investigation the tested compounds did not possess antifungal activity.
Azam, M. Afzal,Suresh, Bhojraj,Kalsi, Sandip S.,Antony, A. Shinesh
scheme or table
p. 114 - 122
(2011/06/09)

Synthesis and antimicrobial activity of new 1,2,4-triazolo [3,4-b]-1,3,4-thiadiazoles
A new series of 3-alkyl-6-aryloxy-1,2,4-triazolo [3,4-b] 1,3,4-thiadiazoles (4a-j) were synthesized by condensation of 3-alkyl-4-amino-5-mercapto-1,2,4- triazoles (2) with aryloxy acetic acids (3) in presence of POCI3. The structures of the newly synthesized compouds were assigned on the basis of IR, 1H NMR and Mass spectral data. All the new compounds were evaluated for their in-vitro antibacterial and antifungal activity.
Revanasiddappa,Subrahmanyam,Satyanarayana
p. 195 - 196
(2013/09/23)

Design, synthesis and in vitro antibacterial/antifungal evaluation of novel 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)quinoline-3-carboxylic acid derivatives
A series of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)quinoline-3-carboxylic acid (norfloxacin) derivatives were prepared according to the principle of combinating bioactive substructures and tested for their activities against five plant pathogenic bacteria and three fungi in vitro. The preliminary bioassays indicated that almost all synthesized target compounds retained the antibacterial activities of norfloxacin and had some antifungal activities as carboxylic acid amide compounds. The activities of compounds 1 and 22 against Xanthomonas oryzae were better than norfloxacin and all tested compounds had better antibacterial activities as compared to the agricultural streptomycin sulfate (a commercial bactericide) against X. oryzae, Xanthomonas axonopodis and Erwinia aroideae. Additionally, compounds 2 and 20 displayed good antifungal activities against Rhizoctonia solani and their inhibition of growth reached 83% and 94% respectively at the concentration of 200 mg/L.
Yu, Zhiyi,Shi, Guanying,Sun, Qiu,Jin, Hong,Teng, Yun,Tao, Ke,Zhou, Guoping,Liu, Wei,Wen, Fang,Hou, Taiping
scheme or table
p. 4726 - 4733
(2010/01/06)

THIADIAZOLE DERIVATIVES, INHIBITORS OF STEAROYL-COA DESATURASE
The present invention relates to substituted thiadiazole compounds of the formula (I) and pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds for modulating SCD activity.
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Page/Page column 73

(2008/12/07)

Synthesis and anti-inflammatory activity of 2-aryloxy methyl oxazolines
A series of potential biologically active 2-aryloxy methyl oxazolines 3a-n have been synthesized from substituted hydroxybenzenes 1a-n with good chemical yield. The compounds 3a-n were screened for their anti-inflammatory, ulcerogenic, cyclooxygenase activities and also for their acute toxicity. The potency of the compounds was compared with that of the standard drugs, aspirin and phenyl butazone. The outcome indicates that compounds 3b (48.2%), 3h (48.5%) and 3l (46.5%) offered significant anti-inflammatory activity with low ulcerogenic activity than the standard drugs.
Khanum, Shaukath Ara,Khanum, Noor Fatima,Shashikanth
body text
p. 4597 - 4601
(2009/04/06)

Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm.
Hidaka, Koushi,Kimura, Tooru,Ruben, Adam J.,Uemura, Tsuyoshi,Kamiya, Mami,Kiso, Aiko,Okamoto, Tetsuya,Tsuchiya, Yumi,Hayashi, Yoshio,Freire, Ernesto,Kiso, Yoshiaki
scheme or table
p. 10049 - 10060
(2009/04/07)

A rapid and high-yield synthesis of aryloxyacetic acid in one pot under microwave irradiation and phase transfer catalysis conditions
A series of aryloxyacetic acid 3a-h has been synthesized in one pot under microwave irradiation and phase transfer catalysis conditions. By the optimization of the reaction condition, a rapid, high-yield and efficient method for the preparation of aryloxyacetic acid is reported.
Wei, Tai-Bao,Liu, Hong,Li, Man-Lin,Zhang, You-Ming
p. 1312 - 1314
(2007/10/03)

Synthesis of Aryloxyacetic Acids, Esters, and Hydrazides Assisted by Microwave Irradiation
Under microwave irradiation on clay a series of transformations of a number of phenols into their aryloxyacetic acids 3 and then their methyl esters 4 and hydrazides 5 has been achieved efficiently in good yields.
Hamid, Hamida M. Abdel,Ramadan, El Sayed,Hagar, Mohamed,El Ashry, El Sayed H.
p. 377 - 382
(2007/10/03)

Synthesis and biological activity of some bistriazole derivatives
A series of bis-(4-amino-5-mercapto-triazol-3-yl)alkanes, their Schiff bases and bis-(1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-4-yl)alkanes have been synthesized. The newly synthesized compounds have been screened for their antibacterial properties. Compounds 5h and 9f exhibit greater degree of antibacterial activity than the standard, Furacin.
Holla, B. Shivarama,Veerendra,Shivananda,Kumari, N. Sucheta
p. 2010 - 2014
(2007/10/03)

Synthesis and structure-activity relationships of a novel series of HIV-1 protease inhibitors encompassing ABT-378 (Lopinavir)
The HIV protease inhibitor ABT-378 (Lopinavir) has a 2,6-dimethylphenoxyacetyl group in the P-2′ position. Analogues in which this group is replaced with various substituted phenyl or heteroaryl groups were synthesized and the structure-activity relationships explored.
Sham, Hing L.,Betebenner, David A.,Chen, Xiaoqi,Saldivar, Ayda,Vasavanonda, Sudthida,Kempf, Dale J.,Plattner, Jacob J.,Norbeck, Daniel W.
p. 1185 - 1187
(2007/10/03)

Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors
PCT No. PCT/US94/09139 Sec. 371 Date Jan. 24, 1996 Sec. 102(e) Date Jan. 24, 1996 PCT Filed Aug. 23, 1994 PCT Pub. No. WO95/06030 PCT Pub. Date Mar. 2, 1995The invention relates to sulfonamide-containing hydroxyethylamine protease inhibitor compounds, their process of making, composition and method of use for inhibiting retroviral proteases such as human immunodeficiency virus.
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(2008/06/13)

Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine
We designed and synthesized a new class of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety. A systematic evaluation of structure - activity relationships for HIV protease inhibition, anti-HIV activities, and pharmacokinetic profiles has led to the delineation of a set of structural characteristics that appear to afford an orally available HIV protease inhibitor. Optimum structures, exemplified by 21f (JE-2147), incorporated 3-hydroxy-2- methylbenzoyl groups as the P2 ligand, (R)-5,5-dimethyl-1,3-thiazolidine-4- carbonyl (Dmt) residue at the P1' site, and 2-methylbenzylcarboxamide group as the P2' ligand. The present study demonstrated that JE-2147 has potent antiviral activities in vitro and exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals.
Mimoto, Tsutomu,Kato, Ryohei,Takaku, Haruo,Nojima, Satoshi,Terashima, Keisuke,Misawa, Satoru,Fukazawa, Tominaga,Ueno, Takamasa,Sato, Hideharu,Shintani, Makoto,Kiso, Yoshiaki,Hayashi, Hideya
p. 1789 - 1802
(2007/10/03)

ALPHA- AND BETA-AMINO ACID HYDROXYETHYLAMINO SULFONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS
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(2008/06/13)

Synthesis of 1,1,1-trichloro-2,2-bis-(carboxymethoxyaryl)ethanes as potential antimicrobial and insecticidal agents
Some new 1,1,1-trichloro-2,2-bis-(carboxymethoxyaryl)-ethanes 2a-t have been synthesised by the treating aryloxyacetic acid (two moles) with chloral hydrate (1 mole) in the presence of catalytic amount of conc. sulphuric acid. The aryloxyacetic acid are prepared by the reaction of substituted phenols with chloroacetic acid in the presence of aq. sodium hydroxide. The antimicrobial activity of these compounds have been assayed against various Gram+ve, Gram-ve bacteria and fungi. The constitution of the products have been elucidated by IR, 1H NMR and mass spectral data and elemental analyses.
Purohit,Shah
p. 618 - 622
(2007/10/03)

Skeletal Rearrangements Preceding CO Loss from Metastable Phenoxymethylene Ions Derived from Phenoxyacetic Acid and Anisole
The loss of CHO2(.) from the molecular ion of phenoxyacetic acid and the expulsion of an H(.) atom from ionized anisole lead to phenoxymethylene ions, which fragment predominantly by CO loss on the microsecond time-scale.Carbon-13 labelling reveals that ca. 90percent of the CO molecules expelled from the metastable ions derived from phenoxyacetic acid incorporate the carbon atom from the 1-position of the phenyl group of the parent compound, whereas the residual CO molecules contain one of the other carbon atoms of the aromatic ring.The 2-fluoro- and 2-methylphenoxymethylene ions derived from the appropriate aryloxyacetic acids behave similarly, i.e. the carbon atom of the methylene group of the parent compound is not incorporated in the expelled CO molecules.In contrast, ca. 45percent of the CO molecules eliminated from the metastable phenoxymethylene ions formed from ionized anisole contain the carbon atom of the methyl group, while the remaining part contains the carbon atom from the 1-position of the phenyl ring of the parent compound.This result is taken as evidence for the occurrence of a skeletal rearrangement of the anisole molecular ion leading to an interchange between the carbon atom of the methyl group and the carbon atom at the 1-position of the ring.The elimination of CO from the metastable ions generated from either phenoxyacetic acid or anisole gives rise to a composite metastable peak.Conclusive evidence as to the formation of (+) isomers other than the phenoxymethylene ion is not obtained, indicating that the composite metastable peak is a result of two competing reactions both leading to CO loss.Possible mechanisms of these reactions are discussed together with the mechanism of the skeletal rearrangement of the molecular ion of anisole prior to H(.) loss.
Molenaar-Langeveld, Tineke A.,Ingemann, Steen,Nibbering, Nico M. M.
p. 1167 - 1178
(2007/10/02)

Synthesis and Antimicrobial Activity of N-piperazines/morpholines
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Chaurasia, Sunita,Srivastava, Savitri D.
p. 45 - 46
(2007/10/02)

Synthesis and screening of antimicrobial and anti-inflammatory activities of aryloxy derivatives of benzimidazoles
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Purohit,Srivastava
p. 163 - 165
(2007/10/02)

Synthesis and biological evaluation of some novel N-[2-(phenoxy/bromo/nitro/substituted-phenoxy)acetyl/propionyl] carbazole
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Jain,Srivastava
p. 775 - 776
(2007/10/02)

Dealkylation of Activated Alkyl Aryl Ethers Using Lithium Chloride in Dimethylformamide
Alkyl aryl ethers having electron-withdrawing substituents in the ortho or para positions are esily cleaved with lithium chloride in dimethylformamide.
Bernard, Angela M.,Ghiani, M. Rossella,Piras, Pier Paolo,Rivoldini, Antonio
p. 287 - 289
(2007/10/02)

POLYMER SUPPORTED REAGENTS: USE OF ANION EXCHANGE RESIN IN THE SYNTHESIS OF ARYLOXY ACETIC ACIDS
Phenoxides supported on Amberlite IRA 400 on reaction with sodium salt of chloroacetic acid gave corresponding aryloxy acetic acid in high yields.Interestingly nitrophenols, 4-hydroxy coumarin and p-hydroxy ethylbenzoate gave excellent yields of the product.
Deshmukh, J. G.,Jagdale, M. H.,Mane, R. B.,Salunkhe, M. M.
p. 479 - 484
(2007/10/02)