- Linear free energy relationships of half-wave reduction potentials of (E)-4-aryl-4-oxo-2-butenoic acids
-
Half-wave reduction potentials of a set of twelve (E)-4-aryl-4-oxo-2-butenoic acids obtained by direct current polarography in methanol are reported. E1/2 is correlated with Hammett sigma values as well as with values of frontier molecular orbitals calculated at a semiempirical molecular orbital level. Constant potential electrolysis of a representative compound shows that the first polarographic wave corresponds to one-electron reduction. The isolation of the product proves reduction of the activated double bond.
- Pastor, Ferenc T.,Drakuli?, Branko J.
-
-
Read Online
- Calorimetric Approach and Simulation for Scale-Up of a Friedel-Crafts Reaction
-
The present study, on the optimisation of the scale-up of a Friedel-Crafts acylation, joins together experimental calorimetric techniques and simulation techniques. The adopted methodology involved the execution of isothermal tests at different temperatures, using the reaction calorimeter RC1, to obtain the heat flow versus time data. These data were used to perform a kinetic study of the reaction by using the simulation software BatchCAD. The reliability of the adopted kinetic model was confirmed by comparing the experimental data obtained by operating the desired reaction in adiabatic mode (in a PhiTec II calorimeter) with the predictions of the kinetic model in the same conditions. Using this kinetic equation it was possible to simulate the process under pilot-plant conditions. The good agreement between the model predictions and the experimental data confirmed the accuracy of the kinetic equations. Finally several large-scale production-plant simulations were carried out varying both dosing time and reaction temperature to maximise the space/time yield and minimise the thermal risks. This led to a high quality and safe process, saving a large part of the time (and money) usually spent in traditional scale-up procedures.
- Gigante, Lucia,Lunghi, Angelo,Martinelli, Simone,Cardillo, Paolo,Picello, Luca,Bortolaso, Roberto,Galvagni, Marco,Rota, Renato
-
-
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)
-
- Asymmetric hydrogenation reaction γ - or δ - ketonato compound (by machine translation)
-
The invention relates to the field, of organic chemistry, specifically γ - or δ - keto acid compound asymmetric hydrogenation reaction, reaction formula as follows : Wherein R is H,C. 1 - C6 An alkyl or halogen, is R 1 - 5 in number of substituents . wherein n is 1 or 2;Cat. is a chiral spiro pyrimidyl phosphine ligand iridium complex . and γ - or δ - keto acid compound is subjected to an internal esterification reaction to further prepare a lactone compound. (by machine translation)
- -
-
Paragraph 0048-0053
(2020/03/06)
-
- Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones
-
A highly efficient asymmetric hydrogenation of ?- A nd ?-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active ?- A nd ?-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.
- Hua, Yun-Yu,Bin, Huai-Yu,Wei, Tao,Cheng, Hou-An,Lin, Zu-Peng,Fu, Xing-Feng,Li, Yuan-Qiang,Xie, Jian-Hua,Yan, Pu-Cha,Zhou, Qi-Lin
-
supporting information
p. 818 - 822
(2020/02/15)
-
- 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
-
-
- 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)
-
- Synthesis of Enantiopure γ-Lactones via a RuPHOX-Ru Catalyzed Asymmetric Hydrogenation of γ-Keto Acids
-
A RuPHOX?Ru catalyzed asymmetric hydrogenation of γ-keto acids has been developed, affording the corresponding enantiopure γ-lactones in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 10000 S/C) under the indicated reaction conditions and the resulting products can be transformed to several enantiopure building blocks, biologically active compounds and enantiopure drugs. (Figure presented.).
- Li, Jing,Ma, Yujie,Lu, Yufei,Liu, Yangang,Liu, Delong,Zhang, Wanbin
-
supporting information
p. 1146 - 1153
(2019/01/30)
-
- 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)
-
- Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines
-
By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.
- Chen, Hui,Zhao, Sihan,Cheng, Shaobing,Dai, Xingjie,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
-
p. 1672 - 1683
(2019/04/08)
-
- Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
-
A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
- Duhamel, Thomas,Mu?iz, Kilian
-
supporting information
p. 933 - 936
(2019/01/23)
-
- Synthesis of Deuterium-Labeled 1,1,6-Trimethyl-1,2-dihydronaphthalene (TDN) and Quantitative Determination of TDN and Isomeric Vitispiranes in Riesling Wines by a Stable-Isotope-Dilution Assay
-
The C13-norisoprenoid aroma compounds 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN) and isomeric 2,10,10-trimethyl-6-methylene-1-oxaspiro[4.5]dec-7-enes, so-called vitispiranes, are considered to be biosynthetically related. They occur at higher concentrations in bottle-aged Riesling wines especially and are important contributors to the varietal aroma of Riesling wines. Because of the variation of the quantitative methods and data reported in the literature, a redetermination of concentration levels for both free and total TDN and isomeric vitispiranes, especially in German Riesling wines, was performed using a stable-isotope-dilution assay (SIDA). For this purpose, a novel six-step synthetic route to TDN and deuterium-labeled TDN was developed. A standardized sample preparation for TDN and vitispiranes and a rapid acid-hydrolysis method at genuine wine-pH conditions for the conversion of the precursors into TDN and vitispiranes were also developed. Automated HS-SPME was applied to 250 wine samples from two wine competitions, and analysis was performed by gas chromatography-mass spectrometry with selected-ion monitoring (GC-SIM-MS) as well as selected-reaction monitoring (GC-SRM-MS).
- G?k, Recep,Bechtloff, Pia,Ziegler, Michael,Schmarr, Hans-Georg,Fischer, Ulrich,Winterhalter, Peter
-
p. 6414 - 6422
(2019/06/07)
-
- 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)
-
- Method for preparing pemetrexed disodium key intermediate
-
The invention discloses a method for preparing a pemetrexed disodium key intermediate (I). The method comprises the following steps: carrying out classical Friedenylation and esterification reactionson raw materials comprising toluene and succinic anhydride to obtain methyl 3-(4-methylphenyl)-4-oxobutanoate, carrying out oxygen or air oxidation on the methyl 3-(4-methylphenyl)-4-oxobutanoate under the catalysis of N-hydroxyphthalimide (NHPI) and cobalt acetate to obtain 4-(methoxy-4-oxobutylcarbonyl)benzoic acid, and carrying out selective reduction, selective oxidation, esterification and bromination reactions on the obtained oxidation product to prepare methyl 4-(3-bromo-4-oxobutyl)benzoate. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, simplicity in treatment, good yield and good purity of the product, and suitableness for industrial production.
- -
-
Paragraph 0053; 0054; 0055; 0056; 0057
(2018/03/28)
-
- 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
-
-
- Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists
-
A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB1 receptors (Ki values of 44.6 nM for CB1 receptors and >40 μM for CB2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB1 receptors with Ki values of 75.5 and 73.2 nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB1 receptor in the [35S]-GTPγS binding assays, and none showed adequate predictive blood–brain barrier permeation, exhibiting low estimated LD50. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB1 receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist.
- Murineddu, Gabriele,Deligia, Francesco,Ragusa, Giulio,García-Toscano, Laura,Gómez-Ca?as, María,Asproni, Battistina,Satta, Valentina,Cichero, Elena,Pazos, Ruth,Fossa, Paola,Loriga, Giovanni,Fernández-Ruiz, Javier,Pinna, Gerard A.
-
p. 295 - 307
(2017/12/26)
-
- Unravelling the Nucleophilicity of Butenolides for 1,6-Conjugate Addition to p-Quinone Methides: A Direct Access to Diversely Substituted Butenolide-Derived Diarylmethanes
-
A Lewis acid catalyzed regioselective C-C bond is constructed through β-addition of deconjugated butenolides with p-quinone methides in a 1,6-conjugate addition manner. Interestingly, Lewis acid catalyzed vinylogous Mukaiyama-Michael reaction of silyloxyfurans with p-QMs proceeds selectively through the α or γ position exclusively. The reaction is mild with broad substrate scope, thus allowing easy access to a wide range of bis-arylated α-/β-/γ-substituted butenolides.
- Sharma, Brijesh M.,Shinde, Dinesh R.,Jain, Ruchi,Begari, Eeshwaraiah,Satbhaiya, Shruti,Gonnade, Rajesh G.,Kumar, Pradeep
-
supporting information
p. 2787 - 2791
(2018/05/17)
-
- 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)
-
- 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 0066
(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.
-
-
- Organoselenium-catalyzed synthesis of oxygen- and nitrogen-containing heterocycles
-
A new and efficient approach for the synthesis of oxygen and nitrogen heterocycles by organoselenium catalysis has been developed. The exo-cyclization proceeded smoothly under mild conditions with good functional group tolerance and excellent regioselectivity. Mechanistic studies revealed that 1-fluoropyridinium triflate is key for oxidative cyclization.
- Guo, Ruizhi,Huang, Jiachen,Huang, Haiyan,Zhao, Xiaodan
-
supporting information
p. 504 - 507
(2016/02/18)
-
- Synthesis, Molecular Docking and Potential Antioxidant Activity of Di/Trisubstituted Pyridazinone Derivatives
-
A number of pyridazinone derivatives bearing substituted benzylidene and heterocyclic/aromatic rings at 4th and 6th positions, respectively were synthesized in good to moderate yields and screened for antioxidant activity. Antioxidant activity of pyridazinone derivatives was evaluated by using several in vitro radical scavenging methods such as 1,1-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2), nitric oxide (NO), reducing power, and metal chelating assay etc. Molegro virtual docker software was used to study the binding affinity of the title compounds with the xanthine oxidoreductase enzyme. Amongst the tested compounds, 5a, 5d, 5g & 5j were found to exhibit excellent antioxidant activity at par with the positive control, ascorbic acid. The molecular docking studies of these compounds demonstrated a good selectivity profile with xanthine oxidoreductase receptors. A preliminary study of the structural-activity relationship showed that the presence of electron withdrawing group and heterocyclic ring on pyridazinone nucleus are associated with the best potency and selectivity profile. It could be proposed that xanthine oxidoreductase receptor may be involved in observed antioxidant activity of pyridazinone derivatives bearing aromatic ring and benzylidene substituents and thus the synthesized compounds are worthy of further exploration.
- Khokra, Sukhbir Lal,Khan, Shah Alam,Thakur, Pramila,Chowdhary, Deepika,Ahmad, Aftab,Husain, Asif
-
p. 739 - 750
(2016/10/04)
-
- 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)
-
- 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)
-
- Synthesis and anti-tubercular activity of 6-(4-chloro/methyl-phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one derivatives against Mycobacterium tuberculosis
-
Two series of 6-(4-Cl-Phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one (3a-e) and 6-(4-CH3-Phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one derivatives (3f-j) were synthesized and evaluated as antitubercular agents against Mycobacterium tuberculosis H37Rv strain by using Microplate Alamar Blue Assay (MABA) method. These compounds (3a-e & 3f-j) were synthesized from 6-(4-Cl-Phenyl)-4,5-dihydropyridazin-3(2H)-one (2a) and 6-(4-CH3-Phenyl)-4,5-dihydropyridazin-3(2H)-one (2b) compounds by reacting with appropriate aldehydes respectively. All title compounds (3a-e & 3f-j) were characterized on the basis of IR, 1HNMR, mass spectral and elemental analysis data. All title compounds (3a-e & 3f-j) were used at 0.2μg/mL to 100μg/mL dose levels for antitubercular activity. Result showed that all the title compounds (3a-e & 3f-j) exhibited less antitubercular activity as compared to the reference drugs streptomycin (MIC value of 6.25μg/mL) and pyrizinamide (MIC value of 3.125μg/mL), except compound 3e, which was equally effective as streptomycin but less effective than pyrazinamide.
- Asif, Mohammad,Singh, Anita
-
p. 500 - 504
(2015/06/22)
-
- 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)
-
- Synthesis of the novel tetrahydropyrazolo[3,4- c ]pyridin-5-one scaffold
-
We report an efficient synthesis of the novel 1,4,6,7-tetra-hydropyrazolo[3,4-c]pyridin-5-one scaffold with the potential for incorporation of alkyl or aryl substituents at the C-3 and N-6 positions. The route utilises a Dieckmann condensation to install the lactam ring, followed by a hydrazine cyclisation to build the fused pyrazole ring.
- Howe, Nicholas J.,Blades, Kevin,Lamont, Gillian M.
-
p. 228 - 232
(2015/03/03)
-
- 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)
-
- 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)
-
- 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)
-
- 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)
-
- 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)
-
- Search for new pharmacophore as antimalarial agent: Synthesis and antimalarial activity of some 2(3H)-furanones bearing quinoline moiety
-
A series of substituted 3-[(substituted-2-chloroquinolin-3-yl)methylene]-5- (substituted-phenyl)-furan-2(3H)-ones (4a-p) have been synthesized and evaluated for their in vitro antimalarial activity against P. falciparum. The title compounds were synthesized by condensing 3-(substituted-benzoyl)propionic acids (3a-d) with substituted 2-chloroquinoline-3-carbaldehydes (2a-d) following modified Perkin's reaction. Compounds 3-[2-chloro-6-methylquinolin-3-yl) methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4n) and 3-[2-chloro-6- methoxyquinolin-3-yl)methylene]-5-(2,4-dimethyl-phenyl)-furan-2(3H)-one (4p) showed promising antimalarial activity with MIC of 10 μg/mL.
- Alam, Mohammad Mumtaz,Sarkar, Deba Priya,Alam, Ozair,Husain, Asif,Marella, Akranth,Akhtar, Mymoona,Shaquiquzzaman, Mohammad,Khanna, Suruchi
-
scheme or table
p. 231 - 236
(2011/10/09)
-
- Synthesis and antitubercular activity of pyridazinone derivatives
-
Two series of pyridazinone derivatives (19-34) were synthesized and evaluated for antitubercular activities against Mycobacterium tuberculosis H37Rv strain. The results illustrated that among the synthesized compounds, compound 25, 5-(4-hydroxy-3-methoxybenzyl)-3-(4-chloro-phenyl)-1,6-dihydro-6-pyridazinone emerged as a lead compound with good antitubercular activity. Four more compounds, (21, 22, 29 & 33) were significant in their antitubercular action.
- Husain, Asif,Ahmad, Aftab,Bhandari, Anil,Ram, Veerma
-
scheme or table
p. 778 - 780
(2012/03/26)
-
- Synthesis and biological evaluation of some new pyridazinone derivatives
-
A series of pyridazinone derivatives (1934) were synthesized with an aim to synthesize safer anti-inflammatory agents. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation (LPO) actions. The percentage inhibition in edema at different time intervals indicated that compounds 20, 26, 28 and 34 exhibited good anti-inflammatory potential, comparable with that of ibuprofen (85.77%) within a range of 67.4877.23%. The results illustrate that 5-(4-fluoro-benzyl)-3-(4-chloro-phenyl) -1,6-dihydro-6-pyridazinone (26) and 5-(4-chloro-benzyl)-3-(4-chloro-phenyl)-1, 6-dihydro-6-pyridazinone (20) showed best anti-inflammatory activity. Furthermore, activity is more in case of chloro substitution as compared with methyl-substitution. The compounds synthesized were also evaluated for their ulcerogenic and LPO action and showed superior gastrointestinal safety profile along with reduction in LPO as compared with that of the ibuprofen.
- Husain, Asif,Drabu, Sushma,Kumar, Nitin,Alam, M. Mumtaz,Ahmad, Aftab
-
scheme or table
p. 742 - 748
(2012/04/04)
-
- 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)
-
- Synthesis of quinoline-attached furan-2(3H)-ones having anti-inflammatory and antibacterial properties with reduced gastro-intestinal toxicity and lipid peroxidation
-
A series of 5-aryl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)- ones (3a-p) were synthesized. The required 3-(substituted benzoyl)propionic acids 2a-d were prepared under Fried?l-Crafts acylation reaction conditions. The substituted 2-chloroquinoline-3-carboxaldehydes 1a-d were synthesized by reaction of substituted phenylethanone oxime with phosphorus oxychloride in presence of dimethylformamide using the Vilsmeier-Haack reaction method. These compounds were screened for their anti-inflammatory and antibacterial activities along with their ulcerogenic and lipid peroxidation potentials. The compounds that showed significant anti-inflammatory activity were further screened for their analgesic activity. The compounds were less toxic in terms of ulcerogenicity as compared to a standard, which was also supported by lipid peroxidation studies. The antibacterial activities were performed against Staphylococcus aureus and Escherichia coli. Compounds 3f, 3n and 3o showed significant activity against both S. aureus and E. coli having an minimum inhibitory concentration (MIC) value of 6.25 μg mL-1. Copyright 2011 (CC) SCS.
- Alam, Mohammad M.,Sarkar, Deba Priya,Husain, Asif,Marella, Akranth,Shaquiquzzaman, Mohammad,Akhter, Mymoona,Shaharyar, Mohammad,Alam, Ozair,Azam, Faizul
-
experimental part
p. 1617 - 1626
(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)
-
- 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)
-
- The conformational diastereomers of 7-substituted-(8Z)-8-chloro-6,7- dihydro-9-(1,2-dihydronaphthalen-4-yl)-5H-benzo[7]annulene derivatives, the question of atropisomerism versus ring inversion
-
Conformational diastereomers of 7-substituted-(8Z)-8-chloro-6,7-dihydro-9- (1,2-dihydro- naphthalen-4-yl)-5H-benzo[7]annulene 1 are observed at room temperature in solution. Two conformational processes are possible in 1, i.e. atropisomerism around the sp2-sp2 pivot bond and ring inversion of cycloheptadiene moiety which together provide four minima structures. The 3J calculation by Haasnoot equation on optimized structures is accordance with the 7-substituents in pseudo equatorial (exo) position in both forms. The barrier to conformational process is determined by dynamic 1H-NMR spectroscopy to be δG≠(365K)=74.5±0.5 kJ/mol. Solvent dependent populations of the two forms are studied in DMSO-d6 and CDCl3, the population ratio is not sensitive to solvent polarity. ARKAT USA, Inc.
- Ranjbar, Parviz Rashidi,Roshan, Hamid
-
scheme or table
p. 40 - 53
(2010/10/03)
-
- The marked difference in conformational behavior of the two diastereomers of 7-substituted-1,1-dichloro-7b-((Z)-8-chloro-6,7-dihydro-5H-benzo[7]annulen-9- yl)-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalene, single crystal X-ray, 1H NMR and AM1 studies
-
The 7-substituted of 1 and 2 were synthesized and conformational analysis carried out. While 7-substituted of 2 show two conformers in solution, 7-substituted of 1 show only one form in solution. AM1 semi-empirical molecular orbital calculations show that the conformation of cycloheptadiene ring in 1 and 2 is a twist boat form. In this conformation, the C-7 substituents can be oriented in pseudo equatorial (exo) and pseudo axial (endo) positions. The 3J calculation with Haasnoot equation on optimized structure of 2 reproduces the observed 3J coupling constants in exo and endo forms. Ring inversion of cycloheptadiene moiety in substituted 2 interconvert the e′-a′ (exo-endo) positions. The 3J calculation on optimized structure of 1 shows that 7-substitution is in pseudo equatorial (exo) direction, as found in the crystal structure of 1a by single crystal X-ray crystallography. The barrier to ring inversion in 2a is determined by dynamic 1H NMR spectroscopy to be ΔG≠(335K) = 68.0 ± 0.5 kJ/mol.
- Roshan, Hamid,Rashidi-Ranjbar, Parviz
-
experimental part
p. 59 - 65
(2011/01/10)
-
- Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles: Synthesis and their anti-inflammatory and analgesic activities
-
Synthesis and biological evaluation of various aroylpropionic acid derivatives containing 1,3,4-Oxadiazole nucleus is reported here. The compounds (3a-w) were synthesized by cyclization of 3-aroylpropionic acids into 1,3,4-oxadiazole nucleus by treating with various aryl acid hydrazides in the presence of POCl3. The structures of new compounds are supported by IR, 1H NMR and MS data. These compounds were tested in vivo for their anti-inflammatory activity. All the compounds tested showed anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. Seven (3c, g, i, j, m, o, p) out of 23 new compounds showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test with very less ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA), which is one of the byproducts of lipid peroxidation. Compound 3i and o showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid induced writhings and 0.7 and 0.65 of severity index respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen. The study showed that the cyclization of carboxylic group of aroylpropionic acids into an oxadiazole nucleus resulted in compounds having good anti-inflammatory and analgesic effects with reduced gastric irritation.
- Akhter, Mymoona,Husain, Asif,Azad, Bismillah,Ajmal
-
scheme or table
p. 2372 - 2378
(2009/12/03)
-
- Reaction of 5-arylfuran-2(3H)-ones with amines
-
5-(4-Chlorophenyl)- and 5-phenylfuran-2(3H)-ones reacted with guanidine carbonate at the methylene group in the unsaturated lactone molecule, leading to the formation of 4-(2-aryl-5-oxo-2,5-dihydrofuran-2-yl)-5-aryltetrahydrofuran-2-ones, while 5-(4-methy
- Potikha,Lysakovskii,Kovtunenko,Turov
-
experimental part
p. 1818 - 1823
(2010/05/03)
-