Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship

Abstract

A series of novel indolizine 2-oxoacetamides were designed and synthesized as PDE4 inhibitors. Preliminary SAR of this new class of compounds revealed key structural features required for high potency. Compounds 1ab and 2a are among the most potent inhibitors of PDE4 with low single nM IC 50 . Cellular activity was demonstrated by the inhibition of TNFa production from human PBMC with IC 50 ranging from 14 to 72 nM. Docking analyses suggest the OH group in 1ab enhance the binding via an H-bond interaction with the PDE4 enzyme.

Invisibility cloaking using pseudomagnetic field for photon

“…An invisibility cloak, which hinders the detection of an object by an external observer, is an old fantasy shown in many movies and sci-fi novels but has only recently become practical through the introduction of transformation optics (TO) and metamaterials [1][2][3][4][5][6][7][8][9][10][11][12]. The key feature of an invisibility cloak is that the waves outside the cloak are left undisturbed as if it is just free space, under arbitrary forms of excitations.…”

Three-dimensional polarization-independent visible-frequency carpet invisibility cloak

“…Our 2010 work [9] demonstrated a microscopic 3D carpet cloak for unpolarized light down to wavelengths of about 1:5 μm. More recent work [12,13] by other groups has demonstrated macroscopic carpet cloaks at visible frequencies, however, only for one linear polarization of light (due to the birefringent calcite used) and in an effectively twodimensional configuration. In this Letter, we miniaturize our 2010 structure by more than a factor of 2, leading to what we believe to be the first 3D carpet cloak for unpolarized visible light.…”

“…The strength of this tool is emphasized by invisibility cloaking [1][2][3], which was long believed to be impossible. In particular, the carpet-cloak concept [4] has inspired experiments by several groups [5][6][7][8][9][10][11][12][13]. In brief, by tailoring a refractive-index profile, the carpet cloak makes a bump in a metal mirror (the carpet) appear flat.…”

Achieving bifunctional cloak via combination of passive and active schemes

“…[1][2][3][4][5][6][7][8] Since the invisibility cloak was experimentally realized in 2006, 3 considerable efforts have been devoted to the realization of practical cloak in various frequencies and much progress has been made. [4][5][6][7][8] In general, almost all reported investigations are limited to a single scheme, which is either the passive one or the active one. The most intensively studied scheme is the passive one, where the object is wrapped with specifically designed materials or structures to make the wave flow round it without any distortion.…”