| Identification | Back Directory | [Name]
5-(N,N-HEXAMETHYLENE)-AMILORIDE | [CAS]
1428-95-1 | [Synonyms]
hma
Amilo
5-HMA
HMA-5
amipromizide
Hexamethyleneamiloride
5-(N,N-HEXAMETHYLENE)-AMILORIDE
AMILORIDE,5-(N,N-HEXAMETHYLENE)-
HMA (5-(N,N-Hexamethylene)amiloride)
5-(N,N-HEXAMETHYLENE)-AMILORIDE USP/EP/BP
5-(N,N-Hexamethylene)amiloride Solution, 100ppm
AMILORIDE, 5-(N,N-HEXAMETHYLENE) >93% NA +/H+ ANTIPORTER INH
3-amino-5-(azepan-1-yl)-6-chloro-N-(diaminomethylene)pyrazinamide
3-amino-5-(azepan-1-yl)-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide
N-(Diaminomethylene)-3-amino-5-(hexamethyleneamino)-6-chloropyrazine-2-carboxamide
3-azanyl-5-(azepan-1-yl)-N-[bis(azanyl)methylidene]-6-chloro-pyrazine-2-carboxamide
3-Amino-5-(1-azacycloheptane-1-yl)-6-chloro-N-(aminoiminomethyl)pyrazine-2-carboxamide
3-AMINO-N-(AMINOIMINOMETHYL)-6-CHLORO-5-(HEXAHYDRO-1H-AZEPIN-1-YL)-PYRAZINE-CARBOXAMIDE
3-Amino-5-(hexahydro-1H-azepin-1-yl)-6-chloro-N-(aminoiminomethyl)-2-pyrazinecarboxamide
6-Chloro-3-amino-5-[(hexahydro-1H-azepin)-1-yl]-N-(diaminomethylene)-2-pyrazinecarboxamide
2-Pyrazinecarboxamide, 3-amino-N-(aminoiminomethyl)-6-chloro-5-(hexahydro-1H-azepin-1-yl)- | [Molecular Formula]
C12H18ClN7O | [MDL Number]
MFCD00069211 | [MOL File]
1428-95-1.mol | [Molecular Weight]
311.77 |
| Chemical Properties | Back Directory | [Melting point ]
224-225 °C | [density ]
1.63±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C
| [solubility ]
DMF: 3mg/mL; DMSO: 10mg/mL; DMSO:PBS (pH 7.2) (1:4): 0.2mg/mL | [form ]
A crystalline solid | [pka]
8.81±0.46(Predicted) | [color ]
Light yellow to yellow | [InChI]
1S/C12H18ClN7O/c13-8-10(20-5-3-1-2-4-6-20)18-9(14)7(17-8)11(21)19-12(15)16/h1-6H2,(H2,14,18)(H4,15,16,19,21) | [InChIKey]
RQQJJXVETXFINY-UHFFFAOYSA-N | [SMILES]
N\C(N)=N\C(=O)c1nc(Cl)c(nc1N)N2CCCCCC2 |
| Safety Data | Back Directory | [Hazard Codes ]
T | [Risk Statements ]
23/24/25 | [Safety Statements ]
22-36/37/39-45 | [RIDADR ]
2811 | [WGK Germany ]
3
| [HazardClass ]
6.1(b) | [PackingGroup ]
III | [Storage Class]
6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | [Hazard Classifications]
Acute Tox. 3 Dermal
Acute Tox. 3 Inhalation
Acute Tox. 3 Oral |
| Hazard Information | Back Directory | [Description]
5-(N,N-hexamethylene)-Amiloride (HMA) is a derivative of amiloride with diverse biological activities. It is an allosteric antagonist of adenosine A2A receptors (Ki = 3.3 μM). HMA inhibits the cation-selective ion channel formed by the HIV-1 viral protein Vpu when used at a concentration of 50 μM, as well as budding of virus-like particles in HeLa cells expressing the HIV-1 proteins Gag and Vpu when used at a concentration of 10 μM. It also blocks the cation-selective ion channels formed by the hepatitis C virus (HCV) protein p7. HMA (40 μM) induces necrosis in and reduces the viability of MCF-7, MDA-MB-231, T47D, SK-BR-3, Met-1, and NDL breast cancer cells but not cardiomyocytes or uterine, pulmonary, and renal epithelial cells. HMA protects against post-ischemic contractile dysfunction and reduces coronary effluent creatine phosphokinase activity in a model of ischemia-reperfusion injury using isolated rat right ventricular free walls. | [Uses]
5-(N,N-Hexamethylene)-amiloride (Hexamethylene amiloride) derives from an amiloride and is a potent Na+/H+ exchanger inhibitor, which decreases the intracellular pH (pHi) and induces apoptosis in leukemic cells. 5-(N,N-Hexamethylene)-amiloride (Hexamethylene amiloride) is also an inhibitor of the HIV-1 Vpu virus ion channel and inhibits mouse hepatitis virus (MHV) replication and human coronavirus 229E (HCoV229E) replication in cultured L929 cells with EC50s of 3.91 μM and 1.34 μM, respectively[1][2]. | [Definition]
ChEBI: A member of the class of pyrazines that is amiloride in which the two amino hydrogens at position N-5 are replaced by a hexamethylene moiety, resulting in the formation of an azepane ring. | [Biochem/physiol Actions]
Inhibitor of Na+/H+ antiport. | [in vivo]
5-(N,N-Hexamethylene)-amiloride (2.5 mg/kg; i.v.; single dose) shows short half-life and lowly oral bioavailability of 4.5%[3].
In vivo pharmacokinetics in mice or rat model[3]
Dosage: 2.5 mg/kg
Administration: Intravenous injection; single does; collected 10 min and 60 min after treatment.
| t1/2 (h) | Plasma CLint (mL/min/kg) | Plasma Vss (L/kg) | Plasma AUC0-inf (h·μM) | B/P ratio | Blood CL (mL/min/kg) | Blood Vss (L/kg) | | Female Balb/c mice | 0.62 | 86 | 2.0 | 1.5 | 1.5 | 59 | 1.4 | | Sprague Dawley rats | 3.2 | 83.5 | 5.3 | 1.6 | 1.8 | 46.2 | 2.9 | | % IV dose excreted in urine (0-24 h) | Renal Blood CL (mL/min/kg) | Non-Renal Blood CL (mL/min/kg) | | | | | | Sprague Dawley rats | 0.5 | 0.2 | 46.0 | | | | |
Note: B/P means blood-to-plasma partitioning ratio; female Balb/c mice (17-27 g, non-fasted); male Sprague Dawley rats (238-325 g, overnight-fasted).
| [IC 50]
HIV-1 | [References]
[1] Rich IN, et al. Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na(+)/H(+) exchanger. Blood. 2000 Feb 15;95(4):1427-34. PMID:10666221
[2] Wilson L, et al. Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication. Virology. 2006 Sep 30;353(2):294-306. Epub 2006 Jul 3. DOI:10.1016/j.virol.2006.05.028
[3] Buckley BJ, et al. Systematic evaluation of structure-property relationships and pharmacokinetics in 6-(hetero)aryl-substituted matched pair analogs of amiloride and 5-(N,N-hexamethylene)amiloride. Bioorg Med Chem. 2021 May 1;37:116116. DOI:10.1016/j.bmc.2021.116116 |
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