Synthesis of new cyclic imides derivatives with potential hypolipidemic activity

Abstract

Certain new nitrogen-substituted derivatives of cyclic imides phthalimide (a), 1, 8-naphthalimide (b), and diphenimide (c), were synthesized aiming to obtain potent hypolipidemic agents. Thus, 2-(N-imido) propanoic acids, 2-(N-phthalimido)-2-methylpropionic acid, and their ethyl esters were synthesized (Target derivative A). Also their corresponding N-substituted-2-(N-imido) propionamides and 2-(N-phthalimido)-2-methylpropionamides were prepared (Target derivative B). In addition, N-phthalimidomethyleneoxy acetate was prepared. Some of the newly prepared compounds were subjected to 3D studies and were found to be superimposed on Clofibrate, which is the first generation of fibrate drugs. The preliminary evaluation of hypolipidemic activity of the newly prepared compounds against triton WR-1339-induced hyperlipidemia in rat showed that several derivatives have demonstrated significant lowering of serum total cholesterol and triglyceride levels at dose of 150 mg/kg/i.p. comparing with Fenofibrate which is one of the second generations of fibrate drugs.

Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis

“…[ 53 ] Next, thioacetic acid derivatives 5a–d were prepared by heating the appropriate potassium salt 3a–d with chloroacetic acid 4 in dry dimethylformamide/potassium iodide mixture using a water bath. The final compounds 8a–d were furnished using a mixed anhydride method [ 54–57 ] which involves reaction of the appropriate thioacetic acid derivatives 5a–d with ethyl chloroformate 6 followed by 3‐aminopiperidine‐2,6‐dione 7 using 2 mole equivalent of Et 3 N. Infrared (IR) spectra of compounds 8a–d showed the presence of bands for NH, amide, and imide carbonyls and the absence of bands for the carboxylic group. Also, the 1 H nuclear magnetic resonance (NMR) spectra showed two signals at about 8.72 and 10.85 ppm attributed to amide and imide protons, respectively and lacked the signal assigned for carboxylic proton.…”

“…[53] Next, thioacetic acid derivatives 5a-d were prepared by heating the appropriate potassium salt 3a-d with chloroacetic acid 4 in dry dimethylformamide/potassium iodide mixture using a water bath. The final compounds 8a-d were furnished using a mixed anhydride method [54][55][56][57] which involves reaction of the appropriate thioacetic acid derivatives 5a-d with ethyl chloroformate 6 followed On the other hand, the ester derivatives 11a,b were prepared by refluxing the appropriate acid 5b,d in absolute ethanol in the presence of sulfuric acid. [58] Then, the acid hydrazides 12a,b were prepared by stirring the appropriate ethyl acetate ester 11a,b in ethanol at room temperature for 30 min.…”

Synthesis of N‐aminophalimides derived from α‐amino acids: Theoretical study to find them as HDAC8 inhibitors by docking simulations and in vitro assays

“…Phthalimide is an aromatic imide with two carbonyl groups bounded to amine moiety and used in organic synthesis for the preparation of a wide variety of compounds with different substituents in both the aromatic ring and the nitrogen atom. These compounds are attractive for their biological activities (Sharma et al, 2010) among them, as antibacterial, antifungal, antimicrobial, anticancer (Ahmed et al, 2016; Akgün et al, 2012; Santos et al, 2009; Tandon et al, 2009; Wang et al, 2013), as platelet aggregation, tryptase inhibitors (Krysko et al, 2013; Tetsuhashi et al, 2010), anti‐inflammatory and immunomodulatory prototypes (Leite et al, 2014), hypolipidemic activity (El‐Zahabi et al, 2012), antiangiogenic activity (Nagarajan et al, 2013), and HDAC's inhibitors (Lee et al, 2007; Shinji et al, 2005, 2006).…”

Design, synthesis, spectral analysis and molecular docking studies of some cyclic imide as potential anti breast and cervical cancer agents

“…The cyclic imides are an important class of chemical compounds with wide applications in many fields if they are characterized by their widespread uses in therapeutic activities [9]. The building blocks are distinguished in the preparation of natural products, agricultural chemicals, pharmaceutical drugs and polymers [10][11][12].…”