15001-13-5Relevant articles and documents
Synthesis, crystal structure, magnetic properties and DFT calculations of a mononuclear copper(II) complex: Relevance of halogen bonding for magnetic interaction
Silva, Cassiano P.,Junior, Henrique C.S.,Santos, Igor F.,Bernardino, Alice M.R.,Cassaro, Rafael A.A.,Novak, Miguel A.,Vaz, Maria G.F.,Guedes, Guilherme P.
, p. 395 - 401 (2018)
The synthesis, crystal structure, magnetic properties and DFT calculations of a new mononuclear copper(II) complex containing a pyrazole-based ligand are reported. In the crystal structure of the [CuCl2L2] complex (L = Ethyl 5-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylate), a network of hydrogen bonds connects the molecular units in the crystal packing. The magnetic studies revealed predominant antiferromagnetic interactions among molecular units. Since there are multiple intermolecular contacts that can act as pathway for magnetic interactions, DFT calculations revealed the fundamental role of N–H?Cl short intermolecular contacts in magnetic behavior. Supported by DFT calculation, the magnetic data above 7.0 K was modeled as a regular Heisenberg chain (H=-2J∑i=1n-1S→Ai·S→Ai+1) resulting in a weak magnetic coupling constant (J) of ?2.6 cm?1. Below this temperature, an unusual magnetic behavior for mononuclear copper(II) complexes was observed: divergence between zero-field cooled (ZFC) and field cooled (FC) magnetic susceptibilities and magnetic hysteresis cycles at low temperatures attributed to spin canting along the chain.
The optimization and characterization of functionalized sulfonamides derived from sulfaphenazole against Mycobacterium tuberculosis with reduced CYP 2C9 inhibition
Chen, Hui,Wang, Bin,Li, Peng,Yan, Hong,Li, Gang,Huang, Haihong,Lu, Yu
supporting information, (2021/03/26)
In this study, a series of sulfonamide compounds was designed and synthesized through the systematic optimization of the antibacterial agent sulfaphenazole for the treatment of Mycobacterium tuberculosis (M. tuberculosis). Preliminary results indicate that the 4-aminobenzenesulfonamide moiety plays a key role in maintaining antimycobacterial activity. Compounds 10c, 10d, 10f and 10i through the optimization on phenyl ring at the R2 site on the pyrazole displayed promising antimycobacterial activity paired with low cytotoxicity. In particular, compound 10d displayed good activity (MIC = 5.69 μg/mL) with low inhibition of CYP 2C9 (IC50 > 10 μM), consequently low potential risk of drug-drug interaction. These promising results provide new insight into the combination regimen using sulfonamide as one component for the treatment of M. tuberculosis.
Targeting Pim Kinases and DAPK3 to Control Hypertension
Carlson, David A.,Singer, Miriam R.,Sutherland, Cindy,Redondo, Clara,Alexander, Leila T.,Hughes, Philip F.,Knapp, Stefan,Gurley, Susan B.,Sparks, Matthew A.,MacDonald, Justin A.,Haystead, Timothy A.J.
, p. 1195 - 32,1207 (2018/07/06)
Sustained vascular smooth muscle hypercontractility promotes hypertension and cardiovascular disease. The etiology of hypercontractility is not completely understood. New therapeutic targets remain vitally important for drug discovery. Here we report that Pim kinases, in combination with DAPK3, regulate contractility and control hypertension. Using a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim/DAPK3 inhibitor (HS56) and selective DAPK3 inhibitors (HS94 and HS148) were developed to provide mechanistic insight into the polypharmacology of hypertension. In vitro and ex vivo studies indicated that Pim kinases directly phosphorylate smooth muscle targets and that Pim/DAPK3 inhibition, unlike selective DAPK3 inhibition, significantly reduces contractility. In vivo, HS56 decreased blood pressure in spontaneously hypertensive mice in a dose-dependent manner without affecting heart rate. These findings suggest including Pim kinase inhibition within a multi-target engagement strategy for hypertension management. HS56 represents a significant step in the development of molecularly targeted antihypertensive medications. Carlson et al. use crystal structure-guided medicinal chemistry techniques to develop a dual Pim/DAPK3 inhibitor (HS56) that reduces myosin phosphorylation and contractility in smooth muscle. Their findings reveal the contribution of Pim kinases to the pathology of hypertension, suggesting a novel multi-target engagement strategy for molecularly targeted antihypertensive medications.
