Action of sodium hydrogen sulphite on some quaternary salts of pyridine and its homologues

Structure of sodium hydrogen selenite-selenious acid (1:3) was solved by heavy-atom method and refined anisotropically to R = 0.098 for 1223 unique observed reflections. The title compound crystallizes in the Pc space group with a = 5.756(2), b = 4.911(2), c = 20.010(5) Å, β = 100.48(3)°, V = 556(1) Å3, T = 293 K, (a = 5.763(2), b = 4.878(1), c = 20.03(1) Å, β = 100.48(3)°, V = 554(1) Å3, T = 173 K), Z = 2. The structure consist of HSeO3- anions, molecules of selenious acid and Na+ cations which are octahedrally coordinated with oxygen atoms. The structure is stabilized by a system of hydrogen bonds.

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Screening of 5- and 6-Substituted Amiloride Libraries Identifies Dual-uPA/NHE1 Active and Single Target-Selective Inhibitors

International Journal of Molecular Sciences ◽

10.3390/ijms22062999 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2999

Author(s):

Benjamin J. Buckley ◽

Ashna Kumar ◽

Ashraf Aboelela ◽

Richard S. Bujaroski ◽

Xiuju Li ◽

...

Keyword(s):

Selectivity Ratio ◽

Dual Targeting ◽

Sodium Hydrogen ◽

Type Plasminogen Activator ◽

Single Target ◽

Urokinase Type Plasminogen Activator ◽

Anti Cancer ◽

Sodium Hydrogen Exchanger ◽

A Cell ◽

Cell Invasiveness

The K+-sparing diuretic amiloride shows off-target anti-cancer effects in multiple rodent models. These effects arise from the inhibition of two distinct cancer targets: the trypsin-like serine protease urokinase-type plasminogen activator (uPA), a cell-surface mediator of matrix degradation and tumor cell invasiveness, and the sodium-hydrogen exchanger isoform-1 (NHE1), a central regulator of transmembrane pH that supports carcinogenic progression. In this study, we co‑screened our library of 5- and 6-substituted amilorides against these two targets, aiming to identify single-target selective and dual-targeting inhibitors for use as complementary pharmacological probes. Closely related analogs substituted at the 6-position with pyrimidines were identified as dual-targeting (pyrimidine 24 uPA IC50 = 175 nM, NHE1 IC50 = 266 nM, uPA selectivity ratio = 1.5) and uPA-selective (methoxypyrimidine 26 uPA IC50 = 86 nM, NHE1 IC50 = 12,290 nM, uPA selectivity ratio = 143) inhibitors, while high NHE1 potency and selectivity was seen with 5-morpholino (29 NHE1 IC50 = 129 nM, uPA IC50 = 10,949 nM; NHE1 selectivity ratio = 85) and 5-(1,4-oxazepine) (30 NHE1 IC50 = 85 nM, uPA IC50 = 5,715 nM; NHE1 selectivity ratio = 67) analogs. Together, these amilorides comprise a new toolkit of chemotype-matched, non-cytotoxic probes for dissecting the pharmacological effects of selective uPA and NHE1 inhibition versus dual-uPA/NHE1 inhibition.

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THE QUATERNARY SALTS OF HEXAMETHYLENETETRAMINE

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)88181-9 ◽

1915 ◽

Vol 21 (2) ◽

pp. 455-464

Author(s):

Walter A. Jacobs ◽

Michael Heidelberger

Keyword(s):

Quaternary Salts

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