- Design, synthesis and biological evaluation of 3,4-dihydronaphthalen-1(2H)-one derivatives as Bcl-2 inhibitors
-
Abstract: A series of new 3,4-dihydronaphthalen-1(2H)-one derivatives (6a–f) were designed, and synthesized by the Claisen–Schmidt condensation reaction. Their structures were characterized by NMR, FTIR, and MS spectroscopy. Their antitumor activities against human neoplastic cell lines Hela, Hepg2, K562, THP-1, SW1990, MIA PaCa-2, NCI-H460 and SK-BR-3 by the MTT method exhibited obvious anticancer activities and their cytotoxicities for LO2 cell lines were lower than DOX, especially for 6b and 6d. The inhibition activities against the Bcl-2 protein for 6b was evaluated and the result shows that lipophilic 3,4-dimethoxybenzylidene and 3,4-dihydronaphthalen-1(2H)-one could bind slightly to the active pockets of the Bcl-2 protein.
- Wang, Fuli,Zhang, Rongxiang,Cui, Yong,Sheng, Liping,Sun, Yinping,Tian, Wei,Liu, Xiao,Liang, Shuzeng
-
-
Read Online
- In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold
-
Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.
- Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Ali, Yakub,Nazreen, Syed,Dhulap, Abhijeet,Alam, Perwez,Pasha
-
-
- Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation
-
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that causes severe motor, sensory, and cognitive impairments. Kallikrein-related peptidase (KLK)6 is the most abundant serine protease secreted in the CNS, mainly by oligodendrocytes, the myelin-producing cells of the CNS, and KLK6 is assumed to be a robust biomarker of MS, since it is highly increased in the cerebrospinal fluid (CSF) of MS patients. Here, we report the design and biological evaluation of KLK6's low-molecular-weight inhibitors, para-aminobenzyl derivatives. Interestingly, selected hit compounds were selective of the KLK6 proteolytic network encompassing KLK1 and plasmin that also participate in the development of MS physiopathology. Moreover, hits were found noncytotoxic on primary cultures of murine neurons and oligodendrocyte precursor cells (OPCs). Among them, two compounds (32 and 42) were shown to promote the differentiation of OPCs into mature oligodendrocytes in vitro constituting thus emerging leads for the development of regenerative therapies.
- A?t Amiri, Sabrina,Deboux, Cyrille,Soualmia, Feryel,Chaaya, Nancy,Louet, Maxime,Duplus, Eric,Betuing, Sandrine,Nait Oumesmar, Brahim,Masurier, Nicolas,El Amri, Chahrazade
-
supporting information
p. 5667 - 5688
(2021/05/29)
-
- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
-
Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
-
supporting information
p. 2707 - 2713
(2020/03/30)
-
- Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives
-
Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.
- Sun, Yue,Zhou, Yan-Qiu,Liu, Yin-Kai,Zhang, Hong-Qin,Hou, Gui-Ge,Meng, Qing-Guo,Hou, Yun
-
p. 1631 - 1640
(2020/08/19)
-
- Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
-
Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
- Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
-
-
- Site- And enantiodifferentiating C(sp3)-H oxidation enables asymmetric access to structurally and stereochemically diverse saturated cyclic ethers
-
A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.
- Liu, Lei,Sun, Shutao,Yang, Yiying,Zhang, Dongju,Zhao, Ran
-
supporting information
p. 19346 - 19353
(2020/12/01)
-
- One-Pot Synthesis of 2,5-Disubstituted Furans through In Situ Formation of Allenes and Enolization Cascade
-
A one-pot synthesis of 2,5-disubstituted furans from γ-ketoacids is reported. In situ formation of allenoates by action of chloroformate on carboxylic acid following by enolization of ketone affords furan derivatives by cyclization. The reaction was extended to a wide scope of ketoacids and phosphonium salts. This methodology was applied on levulinic acid and derivatives, one of the biosourced platform chemicals.
- Bernhard, Yann,Gilbert, Joachim,Bousquet, Till,Favrelle-Huret, Audrey,Zinck, Philippe,Pellegrini, Sylvain,Pelinski, Lydie
-
supporting information
p. 7870 - 7873
(2019/12/24)
-
- Synthesis, crystal structures and anti-inflammatory activity of fluorine-substituted 1,4,5,6-Tetrahydrobenzo[ h]quinazolin-2-Amine derivatives
-
Two fluorine-substituted 1,4,5,6-Tetrahydrobenzo[h]quinazolin-2-Amine (BQA) derivatives, namely 2-Amino-4-(2-fluorophenyl)-9-methoxy-1,4,5,6-Tetrahydrobenzo[ h]quinazolin-3-ium chloride, (8), and 2-Amino-4-(4-fluorophenyl)-9-methoxy-1,4,5,6-Tetrahydrobenzo[h]quinazolin-3-ium chloride, (9), both C19H19-FN3O+-Cl-, were generated by Michael addition reactions between guanidine hydrochloride and the -,unsaturated ketones (E)-2-(2-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C18H15FO2, (6), and (E)-2-(4-fluorobenzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, (7). Because both sides of -,unsaturated ketones (6) or (7) can be attacked by guanidine, we obtained a pair of isomers in (8) and (9). Single-crystal X-ray diffraction indicates that each isomer has a chiral C atom and both (8) and (9) crystallize in the achiral space group P21/c. The chloride ion, as a hydrogen-bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and - interactions. Fortunately, the solubilities of (8) and (9) were distinctly improved and can exceed 50 mg ml-1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti-inflammatory activity show that (8) and (9), with o-and p-fluoro substituents, respectively, display more potential for inhibitory effects on LPS-induced NO secretion than starting ketones (6) and (7).
- Sun, Yue,Gao, Zhongfei,Wang, Chunhua,Hou, Guige
-
p. 1157 - 1165
(2019/08/13)
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE IN CRYSTALLINE FORM
-
The present invention pertains to a process for the preparation of polymorph form X of agomelatine, which comprises providing agomelatine, and crystallizing agomelatine in the presence of at least one of an acid and a salt thereof, and to a polymorph form of agomelatine.
- -
-
Page/Page column 38
(2019/05/02)
-
- Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
-
A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C?O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.
- Estopi?á-Durán, Susana,Donnelly, Liam J.,Mclean, Euan B.,Hockin, Bryony M.,Slawin, Alexandra M. Z.,Taylor, James E.
-
supporting information
p. 3950 - 3956
(2019/02/16)
-
- Design, synthesis, and bioactive screen in vitro of cyclohexyl (E)-4-(Hydroxyimino)-4-phenylbutanoates and their ethers for anti-Hepatitis B Virus agents
-
A series of oxime Cyclohexyl (E)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC50 = 63.85 ± 6.26 μM, SI = 13.41) and HBeAg (IC50 = 49.39 ± 4.17 μM, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC50 = 234.2 ± 17.17 μM, SI = 2.2) and HBeAg (IC50 = 249.9 ± 21.51 μM, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18-27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.
- Cui, Xinhua,Zhou, Min,Tan, Jie,Wei, Zhuocai,Wei, Wanxing,Luo, Peng,Lin, Cuiwu
-
-
- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
-
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
-
supporting information
p. 16490 - 16494
(2019/11/03)
-
- Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation
-
A series of oxime ethers with C6-C4 fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel-Crafts reaction, esterification (or amidation), and oximation from p-substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound 5c-1 showed the most potent activity on inhibiting HBsAg secretion (IC50 = 39.93 μM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.
- Tan, Jie,Zhou, Min,Cui, Xinhua,Wei, Zhuocai,Wei, Wanxing
-
-
- An Electrophilic Trifluoromethylthiolation of Silylenol Ethers and β-Naphthols with Diethylaminosulfur Trifluoride and (Trifluoromethyl)trimethylsilane
-
An efficient and general trifluoromethylthiolation of silylenol ethers and β-naphthols have been accomplished employing the combination of diethylaminosulfur trifluoride (DAST) and (trifluoromethyl)trimethylsilane (CF3TMS) as source of electrophilic trifluoromethylthio moiety for the synthesis of α-trifluoromethylthiolated carbonyl compounds and β-naphthols in good yields. Important features of this method include wide functional group tolerance and use of readily available DAST/CF3TMS. Potential of the methodology was demonstrated via the synthesis of α-trifluoromethylthiolated (+)-4-cholesten-3-one and naphthoquinone. (Figure presented.).
- Saravanan, Perumal,Anbarasan, Pazhamalai
-
supporting information
p. 2894 - 2899
(2018/08/17)
-
- 3(2H)-furanones promising candidates for synthesis of new fluorescent organic probes
-
Several novel 3-arylidene-5-(4-memoxy-3-nitrophenyl)-2(3H)-furanones (2a-d) have been successfully prepared and used as precursors for building up of other new heterocyclic architectures such as pyrrolones (4a-c), (5) and unsaturated aroyl-hydrazides (7a-d). These aroyl-hydrazides have been subsequently converted into pyridazinone derivatives (8a-d) by refluxing in HCl/AcOH mixture. Eventually, benzoylation of the hydrazides (7a-c) with benzoyl chloride affords the corresponding N-benzoyl-3(2H)-pyridazinones (9a-c). The structures of all synthesized compounds have been established using elemental analysis and spectral methods. The photophysical (fluorescence and electronic absorption spectra) properties of newly synthesized compounds have also been investigated.
- Soliman, Mohamed H. A.,Hussein, Belal H. M.,Abdel-Moati, Nahla,El-Tamany, El-Sayed H. M.
-
p. 567 - 575
(2019/05/21)
-
- Nickel-Catalyzed Desymmetrizing Cross-Electrophile Coupling of Cyclic Meso-Anhydrides
-
A Ni-catalyzed desymmetrizing cross-electrophile coupling of cyclic meso-anhydrides with aryl triflates has been successfully demonstrated. This is the only example using cyclic meso-anhydrides in cross-electrophile coupling reactions. A diverse array of valuable γ-keto acid building blocks can be generated under these conditions with excellent functional group tolerance and stereochemical fidelity.
- Lin, Tingzhi,Mi, Jianjun,Song, Lichao,Gan, Jiamin,Luo, Pan,Mao, Jianyou,Walsh, Patrick J.
-
supporting information
p. 1191 - 1194
(2018/02/22)
-
- Divergent Access to (1,1) and (1,2)-Azidolactones from Alkenes using Hypervalent Iodine Reagents
-
A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.
- Alazet, Sébastien,Le Vaillant, Franck,Nicolai, Stefano,Courant, Thibaut,Waser, Jerome
-
supporting information
p. 9501 - 9504
(2017/07/22)
-
- Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study
-
Protein kinase B (PknB) is an essential serine/threonine protein kinase required for Mycobacterium tuberculosis (M. tb) cell division and cell-wall biosynthesis. A high throughput screen using PknB identified a (E)-4-oxo-crotonic acid inhibitor, named YH-8, which was used as a scaffold for SAR investigations. A significant improvement in enzyme affinity was achieved. The results indicated that the α,β-unsaturated ketone scaffold and “trans-” configuration are essential for the activity against PknB. And compounds with an aryl group, especially with electron-withdrawing substituents on benzene ring, exhibited four fold potency than that of YH-8.
- Xu, Changliang,Bai, Xiaoguang,Xu, Jian,Ren, Jinfeng,Xing, Yun,Li, Ziqiang,Wang, Juxian,Shi, Jingjing,Yu, Liyan,Wang, Yucheng
-
p. 4763 - 4775
(2017/02/05)
-
- Structure-Based Discovery of Thiosemicarbazone Metalloproteinase Inhibitors for Hemorrhage Treatment in Snakebites
-
The venoms of snakes are composed by many toxins, which are responsible for various toxic effects including intense pain, bleeding disorders, and local tissue damage caused by hemorrhage and necrosis. The snake venom metalloproteinases (SVMPs) are proteolytic zinc-dependent enzymes acting in different hemostatic mechanisms. In this work, a structure-based molecular modeling strategy was used for the rational design, by means of a homology 3D model of an SVMP isolated from Bothrops pauloensis venom (BpMP-I), followed by synthesis and in vitro evaluation of new thiosemicarbazones as the first inhibitors of the B. pauloensis SVMP. Besides being effective for the SVMP inhibition, two molecules were shown to be effective also in vivo, inhibiting hemorrhage caused by the B. pauloensis whole venom. Docking studies on metalloproteinases from other snake species suggest that the thiosemicarbazones activity is not confined to BpMP-I, but seems to be a common feature of metzincins.
- Ferreira, Francis B.,Pereira, Thiago M.,Souza, Dayane L. N.,Lopes, Daiana S.,Freitas, Vitor,ávila, Veridiana M. R.,Kümmerle, Arthur E.,Sant'Anna, Carlos Mauricio R.
-
supporting information
p. 1136 - 1141
(2017/11/15)
-
- Efficient Hydrogenation of Biomass Oxoacids to Lactones by Using NHC–Iridium Coordination Polymers as Solid Molecular Catalysts
-
A series of NHC–iridium coordination polymers have proven to be robust, efficient and recyclable solid molecular catalysts toward the hydrogenation of biomass levulinic acid (LA) to γ-valerolactone. Along with quantitative yields attained at 0.01 mol % catalyst loading under 50 atm of H2, the solid molecular catalyst was readily recovered and reused for 12 runs without obvious loss of the selectivity and activity. Remarkably, up to 1.2×105 TON, an unprecedented value could be achieved in this important transformation. In addition, a number of LA homologues, analogues and derivatives were well tolerated to deliver various intriguing and functional lactones in good to excellent yields, which further confirmed the feasibility of the solid molecular catalysts.
- Liu, Yaoqi,Sun, Zheming,Huang, Changyu,Tu, Tao
-
p. 355 - 360
(2017/02/05)
-
- Oxime and oxime ether compounds with anti-hepatitis B virus activity
-
The invention discloses oxime and oxime ether compounds with anti-hepatitis B virus activity. The structural general formula of the compound is shown in the following description; a HepG 2.2.15 cell experiment proves that the oxime and oxime ether compounds have a certain inhibition function on HBV surface antigens (HBsAg) and e antigens (HBeAg). Under the same condition, the inhibition rate of positive control group lamivudine on HBsAg is only 55.51%, the highest inhibition rate of the oxime and oxime ether compound on HBsAg can achieve 98.67%, and the oxime and oxime ether compounds have the characteristic of low toxicity. The novel oxime and oxime ether compounds disclosed by the invention are one class of nonnucleosides anti-hepatitis B virus activity compound, and are hopefully developed into the new medicine for resisting hepatitis b viruses.
- -
-
Paragraph 0076
(2017/04/20)
-
- Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
-
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
- Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
-
-
- Synthesis under moderate pressure of 3-imidazo[1,2-a]pyridinylidene pyrrol-2-ones
-
Conversion of 3-imidazo[1,2-a]pyridinylidene furan-2-ones into their pyrrol-2-one analogues was achieved efficiently with high yields, using a solution of ammonium hydroxide under moderate pressure conditions. A NMR study showed that the compounds are mainly isolated as E isomers.
- Masurier, Nicolas,Lebrun, Aurélien,Canitrot, Damien,Chezal, Jean-Michel,Moreau, Emmanuel
-
p. 2583 - 2586
(2016/06/01)
-
- Cobalt-catalyzed oxidative cyclization of gem-disubstituted conjugated alkenols
-
Aryl gem-disubstituted conjugated alkenols underwent oxidative cyclization affording 2,5,5-trisubstituted tetrahydrofurans in reasonable yields and good diastereoselectivities using the reductive termination variation of the Mukaiyama aerobic oxidative reaction. Under oxidative termination, the same alkenols produced diols and ketonic by-products via the double hydration and beta-scission competing pathways. Furthermore, the differences in alkenol reactivity under the reductive and oxidative termination conditions were investigated.
- Alves, Tania M.F.,Costa, Mateus O.,Bispo, Beatriz A.D.,Pedrosa, Fabiana L.,Ferreira, Marco A.B.
-
supporting information
p. 3334 - 3338
(2016/07/11)
-
- Synthetic method for drug intermediate 4-p-methoxyphenyl-4-ketobutyric acid of pyridazinone
-
A synthetic method for a drug intermediate 4-p-methoxyphenyl-4-ketobutyric acid of pyridazinone comprises the following steps: adding 0.21mol of anisole, 0.22-0.25mol of acetic acid acetyl chloride, 230ml of dimethylamine and 70-90mol of acetonitrile into a reaction container, controlling a stirring speed to be at 130-150rpm, reducing the solution temperature to 6--8DEG C, adding 0.45-0.47mol of cuprous chloride in batches, after adding, reducing the solution temperature to 2--5 DEG C, standing for 30-38h, adding 100-130ml of phosphoric acid solution, performing vapor distilling to remove a solvent, reducing the solution temperature to 1--3 DEG C, separating out crystal, filtering, dissolving into a sodium sulfite solution, decoloring by a molecular sieve, adding an oxalic acid solution to keep a pH at 4-5, separating out solid, filtering, washing with a salt solution, and dehydrating with a dehydrating agent to obtain 4-p-methoxyphenyl-4-ketobutyric acid, wherein a mass percent of the phosphoric acid solution is 70-75% and the mass percent of the sodium sulfite solution is 30-35%.
- -
-
Paragraph 0013; 0014
(2016/12/01)
-
- One-pot synthesis of tetralin derivatives from 3-benzoylpropionic acids: Indium-catalyzed hydrosilylation of ketones and carboxylic acids and intramolecular cyclization
-
This reducing system was composed of a small amount (1 mol%) of In(OAc)3, Me2PhSiH, and I2 that effectively catalyzed the hydrosilylation of two different carbonyl groups, a ketone and a carboxylic acid found in 3-benzoylpropionic acids, followed by a subsequent intramolecular cyclization that led to the one-pot preparation of tetralin derivatives.
- Sakai, Norio,Kobayashi, Taichi,Ogiwara, Yohei
-
supporting information
p. 1503 - 1505
(2015/11/24)
-
- Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents
-
Butenolide-based eighteen new amide derivatives (1-18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %).
- Ali, Yakub,Alam, Mohammad Sarwar,Hamid, Hinna,Husain, Asif,Dhulap, Abhijeet,Bano, Sameena,Kharbanda, Chetna,Nazreen, Syed,Haider, Saqlain
-
p. 3775 - 3784
(2015/10/06)
-
- Ultrasound-promoted Friedel-Crafts acylation of arenes and cyclic anhydrides catalyzed by ionic liquid of [bmim]Br/AlCl3
-
A simple and efficient method of Friedel-Crafts acylation of arenes with succinic anhydride, phthalic anhydride and glutaric anhydride under the action of 1-butyl-3-ethylimidazolium ([bmim]Br/AlCl3 ([bmim]+) cation (ionic liquid) and ultrasound irradiation is presented. Thy purity of products was tested by GC-MS and their structures evaluated by IR and 1H NMR spectroscopy.
- Fekri, Leila Zare,Nikpassand, Mohammad
-
p. 1825 - 1829
(2015/01/09)
-
- Remote activation of the nucleophilicity of isatin
-
The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield.
- Zari, Sergei,Kudrjashova, Marina,Pehk, Tonis,Lopp, Margus,Kanger, Tonis
-
supporting information
p. 1740 - 1743
(2014/04/17)
-
- Efficient synthesis, anticonvulsant and muscle relaxant activities of new 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6-phenyl-4,5-dihydropyridazin-3(2H) -one derivatives
-
A series of 2-(2-(3-(4-chlorophenyl)-6-oxo-5,6-dihydropyridazin-1(4H)yl) acetyl)hydrazine carbothioamide and 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6- (4-chlorophenyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized, characterized, and evaluated for anticonvulsant activity and muscle relaxant activity. The synthesized compounds 5d (82.75 %) and 5e (85.44 %) showed promising anticonvulsant activity by protection against tonic hind limb extensor phase in maximal electroshock model (MES) at (50 mg/kg) compared to standard drug phenytoin and also compounds 5d (82.75 %), and 5e (85.44 %) showed significant anticonvulsant activity by protection against pentylenetetrazole- induced generalized convulsions in pentylenetetrazole model (PTZ) at (100 mg/kg) compared to standard drug diazepam. On the other hand, compound 5e showed significant muscle relaxant activity (84.57 %) by rotarod and traction test model comparing with diazepam as a standard drug.
- Sharma, Bhawna,Verma, Amita,Sharma, Upendra Kumar,Prajapati, Sunil
-
p. 146 - 157
(2014/03/21)
-
- Iron-catalyzed arene alkylation reactions with unactivated secondary alcohols
-
A simple, iron-based catalytic system allows for the inter- and intramolecular arylation of unactivated secondary alcohols. This transformation expands the substrate scope beyond the previously required activated alcohols and proceeds under mild reaction conditions, tolerating air and moisture. Furthermore, the use of an enantioenriched secondary alcohol provides an enantioenriched product for the intramolecular reaction, thereby offering a convenient approach to nonracemic products.
- Jefferies, Latisha R.,Cook, Silas P.
-
supporting information
p. 2026 - 2029
(2014/05/06)
-
- Mn-catalyzed three-component reactions of imines/nitriles, grignard reagents, and tetrahydrofuran: An expedient access to 1,5-amino/keto alcohols
-
An expedient Mn-catalyzed three-component synthesis of 1,5-amino/keto alcohols from Grignard reagents, imines/nitriles, and tetrahydrofuran (THF) is described, which deviates from the classic Grignard addition to imines/nitriles in THF solvent. THF is split and sewn in an unprecedented manner in the reaction, leading to the formation of two geminal C-C bonds via C-H and C-O cleavage. Mechanistic experiments and DFT calculations reveal radical and organo-Mn intermediates in the catalytic cycle and the α-arylative ring-opening of THF as the key reaction step.
- He, Ruoyu,Jin, Xiqing,Chen, Hui,Huang, Zhi-Tang,Zheng, Qi-Yu,Wang, Congyang
-
supporting information
p. 6558 - 6561
(2014/05/20)
-
- Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
-
Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
-
p. 552 - 559
(2015/02/19)
-
- Enzymatic synthesis of chiral γ-amino acids using ω-transaminase
-
In this study, we successfully synthesized enantiomerically pure (R)- and (S)-γ-amino acids (>99% ee) using ω-transaminase (ω-TA) through kinetic resolution and asymmetric synthesis respectively. The present study demonstrates the high potentiality of ω-TA reaction for the production of chiral γ-amino acids.
- Shon, Minsu,Shanmugavel, Ramachandran,Shin, Giyoung,Mathew, Sam,Lee, Sang-Hyeup,Yun, Hyungdon
-
supporting information
p. 12680 - 12683
(2015/05/20)
-
- Phosphodiesterase inhibitors. Part 5: Hybrid PDE3/4 inhibitors as dual bronchorelaxant/anti-inflammatory agents for inhaled administration
-
(-)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl) -5-methyl-4,5-dihydropyridazin-3(2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti- inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition. Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4,4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics. In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration.
- Ochiai, Koji,Takita, Satoshi,Kojima, Akihiko,Eiraku, Tomohiko,Iwase, Kazuhiko,Kishi, Tetsuya,Ohinata, Akira,Yageta, Yuichi,Yasue, Tokutaro,Adams, David R.,Kohno, Yasushi
-
p. 375 - 381
(2013/02/23)
-
- Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones
-
Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2 H)-ones (2a-p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d , 2-ej and 2m-p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 μM on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 μM. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h.
- Ovais, Syed,Javed, Kalim,Yaseen, Shafiya,Bashir, Rafia,Rathore, Pooja,Yaseen, Raed,Hameed, Alhamzah D.,Samim, Mohammad
-
p. 352 - 358
(2013/10/01)
-
- PROCESS FOR THE PREPARATION OF N-[2- (7-METHOXY-L-NAPHTHYL) ETHYL] ACETAMIDE AND ITS NOVEL CRYSTALLINE FORMS
-
The present invention relates to a process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 and novel crystalline forms of its intermediates as well as the final compound.
- -
-
Page/Page column 32; 33
(2012/04/23)
-
- Triazole incorporated pyridazinones as a new class of antihypertensive agents: Design, synthesis and in vivo screening
-
A number of 6-(substituted phenyl)-2-(4-substituted phenyl-5-thioxo-4,5- dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were designed and synthesized by a sequence of reactions starting from respective aryl hydrocarbons. The final compounds (4a-4u) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 4e, 4i and 4k showed appreciable antihypertensive activity comparable with that of standard hydralazine and propranolol.
- Siddiqui, Anees A.,Mishra, Ravinesh,Shaharyar, Mohammad,Husain, Asif,Rashid, Mohd.,Pal, Palash
-
scheme or table
p. 1023 - 1026
(2011/03/21)
-
- An efficient one-pot synthesis of pyridazinones and phthalazinones using HY-zeolite
-
Figure represented. The first one-pot synthesis of pyridazinones and phthalazinones from arenes, cyclic anhydrides, and ArNHNH2 in the presence of efficient recyclable heterogeneous catalyst, HY-zeolite, in high yield and short reaction time is reported.
- Zare, Leila,Mahmoodi, Nosratollah,Yahyazadeh, Asieh,Mamaghani, Manouchehr,Tabatabaeian, Khalil
-
experimental part
p. 864 - 867
(2011/09/16)
-
- Synthesis, characterization and antihypertensive activity of some new substituted pyridazine derivatives
-
Some new 6-(substituted phenyl)-2-(4-substituted phenyl-5-thioxo-4,5- dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by a sequence of reactions starting from respective aryl hydrocarbons. The final compounds (4a-i) were screened for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 4e and 4i showed appreciable antihypertensive activity.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd,Prakash, Atish,Tailang, Mukul,Kumar, Muneesh,Srivastava, Neeti
-
experimental part
p. 856 - 859
(2012/05/05)
-
- New amides of sulphonamides: Synthesis and biological evaluation
-
A series of amide-derivatives has been synthesized by establishing an amide linkage (-CONH-) between appropriate sulphonamide moiety and different 3-(4-substituted-benzoyl) propionic acids through one-pot reaction. The structures of the newly synthesized compounds were established on the basis of modern analytical techniques. These amides were evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Some of the compounds showed good antiinflammatory activity. Additionally, these derivatives were very low in their ulcerogenic action.
- Husain, Asif,Ahmad, Ausaf,Mujeeb,Akhter, Mymoona
-
experimental part
p. 74 - 77
(2010/08/19)
-
- Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
-
Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP).
- Rist, ystein,Grimstrup, Marie,Receveur, Jean-Marie,Frimurer, Thomas M.,Ulven, Trond,Kostenis, Evi,Hoegberg, Thomas
-
scheme or table
p. 1177 - 1180
(2010/06/15)
-
- Synthesis, characterization and antihypertensive activity of pyridazinone derivatives
-
Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 16, 19, 24, 30, 39, 42 and 45 showed good antihypertensive activity.
- Siddiqui, Anees A.,Mishra, Ravinesh,Shaharyar, Mohammad
-
scheme or table
p. 2283 - 2290
(2010/07/05)
-
- Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3, 4,5-tetrahydropyridazin-3-one derivatives
-
The synthetic pathway for 6-substituted phenyl-2-[{(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl}-methyl]-2,3,4,5-tetrahydropyridazin- 3-one compounds was achieved by a sequence of reactions starting from respective aryl hydrocarbons and is illustrated in Scheme1. All the compounds were tested for their in vitro antifungal activity on five fungal species, namely Candida albicans, Trichophyton rubrum, Aspergillus flavus, Aspergillus niger and Penicillium citrinium. The chloro substituent derivative (compound 5g) showed the highest activity against all the fungal species. The MIC of the standard drug voriconazole was between 0.10 - 0.40 μg/mL against all the fungal species except A. fumigatus. The two electronegative groups of Cl were increasing the activity of 1,2,4-triazole. As we increased the bulky group or aromatic group on benzene ring, there was a decrease of activity as in case of compound l.
- Siddiqui, Anees A.,Ahamad, Syed Rizwan,Mir, Mohammed Shehroz,Hussain, Syed Akhtar,Raish, Mohammed,Kaur, Ravindra
-
experimental part
p. 223 - 228
(2009/04/04)
-
- PHENYLALKYLCARBOXYLIC ACID DELIVERY AGENTS
-
The present invention provides phenylalkylcarboxylic acid compounds and compositions containing such compounds which facilitate the delivery of biologically active agents.
- -
-
Page/Page column 25-26
(2008/12/07)
-
- Kinetics of oxidation of 4-oxoacids by N-chlorosaccharin in aqueous acetic acid medium
-
The oxidation kinetics of substituted and unsubstituted 4-oxoacids (S) by N-chlorosaccharin (NCSA) have been studied in aqueous acetic acid media. The reaction follows first-order kinetics in each of the 4-oxoacids, NCSA and H +. The effect of changes in the electronic nature of the substrate reveals that positive charge develops in the transition state. Based on the kinetic results and product analysis, a suitable mechanism has been proposed for the reaction of NCSA with 4-oxoacids. Springer Science+Business Media, LLC 2007.
- Farook, N. A. Mohamed
-
p. 345 - 356
(2007/12/25)
-
- Asymmetric hydrogenation of α-primary and secondary amino ketones: Efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine
-
Two ss-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of α-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation repI resents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.
- Shang, Gao,Liu, Duan,Allen, Scott E.,Yang, Qin,Zhang, Xumu
-
p. 7780 - 7784
(2008/04/03)
-
- BENZOTHIAZIN-3-ONE COMPOUND AND INTERMEDIATE THEREFOR
-
A medicine which contains as an active ingredient a benzothiazin-3-one-compound represented by the formula (1): (wherein n is 3 or 4; R represents ethyl or hydrogen; and R 1 represents hologeno, alkoxy, haloalkyl, or haloalkoxy) or a pharmaceutically acceptable salt thereof. It is useful as a therapeutic or preventive agent for arthrosis deformans, chondrodegenerative discases such as chronic articular rheumatism, cancers, gingivitis, etc. Also provided are an intermediate for the compound and a process for producing the compound.
- -
-
Page/Page column 33
(2008/06/13)
-
- Asymmetric synthesis of 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids
-
3-Aryl-2-hydroxycyclopent-2-en-1-ones, when subjected to asymmetric oxidation, result in enantiomerically enriched 2-aryl-5-oxotetrahydrofuran-2- carboxylic acids. Electron-donating substituents in the para position of the phenyl ring increase the yield and decrease the enantioselectivity of the process. Georg Thieme Verlag Stuttgart.
- Jogi, Artur,Paju, Anne,Pehk, Tonis,Kailas, Tiiu,Mueuerisepp, Aleksander-Mati,Kanger, Tonis,Lopp, Margus
-
p. 3031 - 3036
(2008/02/08)
-