Synthesis, Structure–Activity Relationship Studies, and ADMET Properties of 3‐Aminocyclohex‐2‐en‐1‐ones as Chemokine Receptor 2 (CXCR2) Antagonists

Herein we describe the synthesis and structure–activity relationships of 3‐aminocyclohex‐2‐en‐1‐one derivatives as novel chemokine receptor 2 (CXCR2) antagonists. Thirteen out of 44 derivatives were found to inhibit CXCR2 downstream signaling in a Tango assay specific for CXCR2, with IC50 values less than 10 μm. In silico ADMET prediction suggests that all active compounds possess drug‐like properties. None of these compounds show significant cytotoxicity, suggesting their potential application in inflammatory mediated diseases. A structure–activity relationship (SAR) map has been generated to gain better understanding of their binding mechanism to guide further optimization of these new CXCR2 antagonists.Combating inflammatory disease: New derivatives of 3‐aminocyclohex‐2‐en‐1‐ones were synthesized and evaluated for their CXCR2 inhibition. Structure– activity relationship studies of these compounds were performed. Several compounds display CXCR2 IC50 values less than 10 μm, and also show selectivity against CXCR2 and low cytotoxicity. In silico ADMET prediction suggests most active compounds possess good drug‐like properties.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143675/1/cmdc201800027.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143675/2/cmdc201800027_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143675/3/cmdc201800027-sup-0001-misc_information.pd

On the Circular Polarisation of Repeating Fast Radio Bursts

Fast spinning (e.g., sub-second) neutron star with ultra-strong magnetic fields (or so-called magnetar) is one of the promising origins of repeating fast radio bursts (FRBs). Here we discuss circularly polarised emissions produced by propagation effects in the magnetosphere of fast spinning magnetars. We argue that the polarisation-limiting region is well beyond the light cylinder, suggesting that wave mode coupling effects are unlikely to produce strong circular polarisation for fast spinning magnetars. Cyclotron absorption could be significant if the secondary plasma density is high. However, high degrees of circular polarisation can only be produced with large asymmetries in electrons and positrons. We draw attention to the non-detection of circular polarisation in current observations of known repeating FRBs. We suggest that the circular polarisation of FRBs could provide key information on their origins and help distinguish different radiation mechanisms.Comment: ApJ accepte

CRAFTS for Fast Radio Bursts : extending the dispersion-fluence relation with new FRBs detected by FAST

We report three new FRBs discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST), namely FRB 181017.J0036+11, FRB 181118, and FRB 181130, through the Commensal Radio Astronomy FAST Survey (CRAFTS). Together with FRB 181123, which was reported earlier, all four FAST-discovered FRBs share the same characteristics of low fluence (1000 pc cm(-3)), consistent with the anticorrelation between DM and fluence of the entire FRB population. FRB 181118 and FRB 181130 exhibit band-limited features. FRB 181130 is prominently scattered (tau(s) 8 ms) at 1.25 GHz. FRB 181017.J0036+11 has full-bandwidth emission with a fluence of 0.042 Jy ms, which is one of the faintest FRB sources detected so far. CRAFTS has started to build a new sample of FRBs that fills the region for more distant and fainter FRBs in the fluence-DME diagram, previously out of reach of other surveys. The implied all-sky event rate of FRBs is 1.24(-0.90)(+1.94) x 5 sky(-1) day(-1) at the 95% confidence interval above 0.0146 Jy ms. We also demonstrate here that the probability density function of CRAFTS FRB detections is sensitive to the assumed intrinsic FRB luminosity function and cosmological evolution, which may be further constrained with more discoveries

Atypical radio pulsations from magnetar SGR 1935+2154

Magnetars are neutron stars with extremely strong magnetic fields, frequently powering high-energy activity in X-rays. Pulsed radio emission following some X-ray outbursts have been detected, albeit its physical origin is unclear. It has long been speculated that the origin of magnetars' radio signals is different from those from canonical pulsars, although convincing evidence is still lacking. Five months after magnetar SGR 1935+2154's X-ray outburst and its associated Fast Radio Burst (FRB) 20200428, a radio pulsar phase was discovered. Here we report the discovery of X-ray spectral hardening associated with the emergence of periodic radio pulsations from SGR 1935+2154 and a detailed analysis of the properties of the radio pulses. The complex radio pulse morphology, which contains both narrow-band emission and frequency drifts, has not been seen before in other magnetars, but is similar to those of repeating FRBs - even though the luminosities are many orders of magnitude different. The observations suggest that radio emission originates from the outer magnetosphere of the magnetar, and the surface heating due to the bombardment of inward-going particles from the radio emission region is responsible for the observed X-ray spectral hardening.Comment: 47 pages, 11 figure

A repeating fast radio burst associated with a persistent radio source

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately 903−111+72 parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications