Dimethyl-diphenyl-propanamide Derivatives As Nonsteroidal Dissociated Glucocorticoid Receptor Agonists

Abstract

A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.

Identification of Potent and Selective Diphenylpropanamide RORγ Inhibitors

“…20 The benzylic stereocenter is known to affect the biological activities of GR modulators. The enantiomers of 4n were separated by chiral HPLC to afford 4n(−) and 4n(+) , assigned according to their optical rotation.…”

Anti-inflammatory and Anti-ulcer Activities of New Fused Thiazole Derivatives Derived from 2-(2-Oxo-2H-chromen-3-yl)thiazol-4(5H)-one

“…Moreover, the 13 C NMR spectrum shoSheme 1. Synthesis of compounds 3, 6a-c and 7a-c wed beside the expected signals, δ 58.6 ppm indicating the presence of the thiazole CH 2 , two signals at δ 164.3, 168.6 ppm equivalent to the two CO groups and a signal at δ 170.3 ppm for the C=N.…”

“…The percentage of ulcer protection was determined as follows. UI was measured by using the following formula: (2) where UI is ulcer index; UN average number of ulcers per animal; US average number of severity score; UP percentage of animals with ulcers. Percentage inhibition of ulceration was calculated as below:…”

“…Thiazole derivatives also exhibit a broad spectrum of medicinal and biological properties, such as antibacterial, antifungal, 1 anti-inflammatory, 2 antiviral, In many report structural modification of the heterocyclic rings through the construction of new heterocyclic nuclei enhances the pharmaceutical applications of the resulting molecules. 15,16 This encouraged our efforts in this work to modify 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetonitrile through its reaction with salicyladehyde to produce a chromen-3-yl)thiazol which was used as the key starting compound for many further heterocyclic transformations.…”

The Uses of 2-Amino-4-Phenylthiazole in the Synthesis of Coumarin, Pyran, Pyridine and Thiazole Derivatives with Antitumor Activities

“…Thiazole derivatives also exhibit a broad spectrum of medicinal and biological properties, such as antibacterial, antifungal [1], anti-inflammatory [2], antiviral [3], antimalarial [4] and anti-HIV activities [5]. Thiazole analogs have also been reported as ligands at estrogen receptors [6], neuropeptide Y5 [7], adenosine receptors [8], and act as inhibitors of human platelet aggregation factor [9], urokinase [10] and poly (ADP-Ribose) polymerase-1 [11].…”