Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acrylamides

Abstract

A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, (E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- (6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.

Synthesis and Biological Evaluation of a Novel Series of 6,8‐Dibromo‐4(3H)quinazolinone Derivatives as Anticancer Agents

“…In the last few years, the attention was oriented towards the synthesis and biological evaluation of quinazoline derivatives as they exhibit a broad spectrum of biological activities. Indeed, several quinazoline derivatives have been reported to possess anticonvulsant , sedative, antihypertensive , vasodilatory , anti‐inflammatory , antibiosis , phosphodiesterase inhibitory , fibrinogen receptor antagonistic , and antitumor activity . Anilinoquinazoline containing compounds were recently approved for the treatment of HER2‐positive metastatic breast cancer .…”

Synthesis of Some <i>N</i>-[(4-Substituted-1-Piperazinyl)-Oxo(Alkyl and Ethylcarbamoyl)]-3-(2-Thiophenyl)Acrylamides as Non-Steroidal Anti-Allergic and Anti-Inflammatory Agents

“…Traditionally symptomatic treatment of allergies and bronchial asthma has been provided by β-sympathomimetic agents, methylxanthines, corticosteroids, and anticholinergics [1][2][3]. Japanese authors have synthesized a series of acrylamide derivatives linked with different piperazines via alkyl chains and proved them as promising anti-allergic candidates (Figure 1(A)) [4][5][6][7].…”

Alkylation of 2,4-(1H,3H)-Quinazolinediones with Dialkyl Carbonates Under Microwave Irradiations

“…Our group has been working on the synthesis of quinazolinone and quinazolinedione derivatives, which are of considerable interest because of their wide array of pharmacological properties [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. We have synthesized heterocycles containing the quinazoline-2,4-dione backbone, which are known to exhibit potential anti-hypertensive properties [ 21 , 22 , 23 , 24 , 25 ]. We have described the synthesis of pelanserine ( 5f ), a potent anti-hypertensive agent [ 26 ], and a several quinazoline-2,4-diones with amino acids and dipeptide, which when tested showed mild to no antihypertensive properties [ 27 ].…”