5399-06-4Relevant articles and documents
Optimizing the Pharmacological Profile of New Bifunctional Antihyperlipidemic/Antioxidant Morpholine Derivatives
Matralis, Alexios N.,Kourounakis, Angeliki P.
, p. 98 - 104 (2019)
Among the causal risk factors directly promoting the development of coronary and peripheral atherosclerosis are reactive oxygen species and elevated low-density lipoprotein plasma levels. We hereby designed new potent squalene synthase (SQS) inhibitors that may simultaneously tackle the oxidative stress induced by lipid peroxidation. Using previously developed morpholine derivatives as a starting point, we conducted extensive structural changes by either substituting or modifying the morpholine ring, aiming at an optimal SQS-antioxidant pharmacological profile. Compounds 2, 3, and 7 emerged as the most potent bifunctional analogues, displaying IC50 values for SQS inhibition of 0.014, 0.16, and 0.51 μM, respectively, and further significantly decreasing lipid peroxidation of hepatic microsomal membranes. The aforementioned activities were also confirmed in vivo since the most promising derivative 2 exhibited a remarkable antihyperlipidemic and antioxidant effect. In conclusion, rational drug design accompanied by structure-activity relationship studies led to compounds combining improved antioxidant and antihyperlipidemic activity that may serve as multifunctional agents against atherosclerosis.
METHOD FOR MANUFACTURING AROMATIC NITRILE COMPOUND
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Paragraph 0228-0229; 0234-0235; 0241-0243; 0252-0263, (2021/03/19)
The present invention provides a method for industrially producing a highly pure aromatic nitrile compound and a highly pure aromatic carboxylic acid compound safely and highly efficiently at low costs. Compound (2) is subjected to Willgerodt reaction in the presence of an additive as necessary, and the obtained amide compound (3) is hydrolyzed and neutralized to give carboxylic acid compound (4). Carboxylic acid compound (4) is reacted with a halogenating agent in the presence of a catalyst as necessary in an organic solvent, and further reacted with an amidating agent, and the obtained amide compound (5) or (6) is reacted with a dehydrating agent to give nitrile compound (1). Alternatively, carboxylic acid compound (4) is reacted with a halogenating agent and a compound represented by the formula R6SO2R7 in the presence of a catalyst as necessary in an organic solvent to give nitrile compound (1). Np is a naphthyl group optionally having substituent(s), R5 is an alkylene group having 1-3 carbon atoms, and other symbols are as described in the DESCRIPTION.
Selective reduction of carbonyl groups in the presence of low-valent titanium reagents
Lin, Wei,Hu, Ming-Hua,Feng, Xian,Fu, Lei,Cao, Cheng-Pao,Huang, Zhi-Bin,Shi, Da-Qing
, p. 2238 - 2242 (2014/04/17)
The chemoselective reduction of several structurally diverse compounds containing carbonyl groups was achieved in the presence of low-valent titanium reagents. This novel synthetic method provides easy access to highly selective reduction of carbonyl groups, and possesses several advantages including one-step procedure, convenient manipulation, good to excellent yields, and short reaction times.
Sulfated tungstate: A green catalyst for synthesis of thiomorpholides via Willgerodt-Kindler reaction
Salim, Suresh D.,Pathare, Sagar P.,Akamanchi, Krishnacharya G.
experimental part, p. 78 - 81 (2012/06/04)
Use of sulfated tungstate as an efficient, green and reusable catalyst for preparation of thiomorpholides via Willgerodt-Kindler reaction pathway is presented. The reaction proceeds under solvent free condition. The advantages of this method are high yiel
Ultrasound-mediated willgerodt-kindler reactions: Non-thermal synthesis of thioacetamides
Mojtahedi, Mohammad M.,Alishiri, Tooba,Abaee, M. Saeed
experimental part, p. 1910 - 1915 (2011/10/08)
Non-thermal, solvent-free condensation of several aryl methyl ketones with amines and elemental sulfur is efficiently conducted using ultrasonic irradiation within short time periods. Consequently, various thioacetamides are conveniently synthesized. Simi
Silica-supported fluoroboric acid (HBF4-SiO2) catalyzed highly productive synthesis of thiomorpholides as activators of l-asparaginase as well as the antioxidant agent
Bandgar, Babasaheb P.,Gawande, Shrikant S.,Warangkar, Suchita C.,Totre, Jalinder V.
experimental part, p. 3618 - 3624 (2010/08/03)
An efficient solvent-free procedure for the synthesis of thiomorpholides in the presence of a catalytic amount of solid-supported fluoroboric acid (HBF4-SiO2) is described. The advantages of this method are high yields, short reaction times, ease of product isolation, low cost, and the catalyst can be recycled for a number of times without significant loss of activity. Three thiomorpholides possessing electron-donating group (4c, 4g, and 4h) were exhibiting excellent stimulatory activities against Erwinia carotovora l-asparaginase. The most potent activator, compound 4h displayed the following kinetic parameters, Km = 75 μM and Vmax = 1000 μmol mg-1 min-1 and KA = 0.985 μM. Furthermore, these compounds (4g, 4h, 4c, 4f, 4a, and 4d) have also shown promising 2,2′-diphenyl-1-picrylhydrazyl (DPPH) reducing antioxidant activity (21-36%) at 1 mM concentration as compared to standard butylated hydroxyl anisole (72% at 1 mM).
Willgerodt-kindler's microwave-enhanced synthesis of thioamide derivatives
Poupaert, Jacques H.,Duarte, Sandro,Colacino, Evelina,Depreux, Patrick,McCurdy, Christopher R.,Lambert, Didier L.
, p. 1959 - 1973 (2007/10/03)
The Willgerodt-Kindler reaction was applied to a series of aromatic aldehydes and ketones. The reactions were performed in a dipolar aprotic solvent (mainly DMF) in the presence of a base catalyst (4-methylmorpholine) and utilized microwave (mw) irradiation. The pulsed mw technique rather than the continuous irradiation was preferred because it limited side reactions and hydrogen sulfide production. While not always superior to the thermal activation of the reaction, the procedure involving repetitive short pulses of microwave irradiation was found to be faster and result in consistently cleaner products. The technique can be easily applied in a fast parallel synthesis process.
A facile synthesis of phenylacetic acids via Willgerodt-Kindler reaction under PTC condition
Alam, Mujahid,Adapa, Srinivas R.
, p. 59 - 63 (2007/10/03)
Phenylacetic acids are efficiently synthesized from acetophenones via thiomorpholides under Phase Transfer Catalytic (PTC) condition. The reaction proceeds efficiently by using triethyl benzyl ammonium chloride (TEBA) as PTC and the reaction time decreased dramatically upto 1/5th (24-5) to afford pure products in good to excellent yield.
