5-(N,N-HEXAMETHYLENE)-AMILORIDE CAS 1428-95-1

Introduction：Basic information about 5-(N,N-HEXAMETHYLENE)-AMILORIDE CAS 1428-95-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

5-(N,N-HEXAMETHYLENE)-AMILORIDE Basic information

• Product Name: 5-(N,N-HEXAMETHYLENE)-AMILORIDE
• Synonyms: 5-(N,N-HEXAMETHYLENE)-AMILORIDE;AMILORIDE,5-(N,N-HEXAMETHYLENE)-;3-AMINO-N-(AMINOIMINOMETHYL)-6-CHLORO-5-(HEXAHYDRO-1H-AZEPIN-1-YL)-PYRAZINE-CARBOXAMIDE;AMILORIDE, 5-(N,N-HEXAMETHYLENE) >93% NA +/H+ ANTIPORTER INH;hma;amipromizide;3-Amino-5-(1-azacycloheptane-1-yl)-6-chloro-N-(aminoiminomethyl)pyrazine-2-carboxamide;3-Amino-5-(hexahydro-1H-azepin-1-yl)-6-chloro-N-(aminoiminomethyl)-2-pyrazinecarboxamide
• CAS: 1428-95-1
• MF: C12H18ClN7O
• MW: 311.77
• Mol File: 1428-95-1.mol

5-(N,N-HEXAMETHYLENE)-AMILORIDE Chemical Properties

• 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
• pka: 8.81±0.46(Predicted)
• form: A crystalline solid
• 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 Information

• 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

5-(N,N-HEXAMETHYLENE)-AMILORIDE Usage And Synthesis

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/kgAdministration: 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