4619-20-9Relevant articles and documents
Linear free energy relationships of half-wave reduction potentials of (E)-4-aryl-4-oxo-2-butenoic acids
Pastor, Ferenc T.,Drakuli?, Branko J.
, p. 734 - 738 (2010)
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.
Calorimetric Approach and Simulation for Scale-Up of a Friedel-Crafts Reaction
Gigante, Lucia,Lunghi, Angelo,Martinelli, Simone,Cardillo, Paolo,Picello, Luca,Bortolaso, Roberto,Galvagni, Marco,Rota, Renato
, p. 1079 - 1082 (2003)
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.
In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold
Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Ali, Yakub,Nazreen, Syed,Dhulap, Abhijeet,Alam, Perwez,Pasha
, (2020/11/27)
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.
Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation
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)
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.
Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones
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)
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.
Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
, (2020/04/07)
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.
Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
supporting information, p. 2707 - 2713 (2020/03/30)
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.
Asymmetric hydrogenation reaction γ - or δ - ketonato compound (by machine translation)
-
Paragraph 0048-0053, (2020/03/06)
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)
Synthesis of Enantiopure γ-Lactones via a RuPHOX-Ru Catalyzed Asymmetric Hydrogenation of γ-Keto Acids
Li, Jing,Ma, Yujie,Lu, Yufei,Liu, Yangang,Liu, Delong,Zhang, Wanbin
supporting information, p. 1146 - 1153 (2019/01/30)
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.).
Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
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)
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.
