40580-59-4

Basic information

• Product Name: Guanadrel
• Synonyms: Guanadrel;1-(1,4-Dioxaspiro[4.5]decan-2-ylmethyl)guanidine;C07035;N-(1,4-Dioxaspiro[4.5]dec-2-ylmethyl)guanidine
• CAS NO: 40580-59-4
• Molecular Formula: C10H19N3O2
• Molecular Weight: 213.2768
• Mol File: 40580-59-4.mol

Chemical Properties

• Boiling Point: 387.9°Cat760mmHg
• Flash Point: 188.4°C
• Appearance: /
• Density: 1.39g/cm³
• Vapor Pressure: 3.2E-06mmHg at 25°C
• Refractive Index: 1.618
• CAS DataBase Reference: Guanadrel(CAS DataBase Reference)
• NIST Chemistry Reference: Guanadrel(40580-59-4)
• EPA Substance Registry System: Guanadrel(40580-59-4)

Safety Data

• Hazardous Substances Data: 40580-59-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Guanadrel is used as an antihypertensive agent for managing essential hypertension. It is particularly useful for treating hypertension in patients who do not respond to thiazide diuretics.
Used in Hypertension Treatment:
Guanadrel is used as an adjuvant drug in thiazide treatment for reaching an optimal level of blood pressure in patients who do not adequately respond to thiazide diuretics alone.

Originator

Hylorel,Pennwalt,US,1983

Manufacturing Process

A mixture of 10.5 g of 1,4-dioxaspiro[4.5]decane-2-methylamine and 8.6 g of 2-methyl-2-thiopseudourea sulfate in 40 ml of water was heated on the steam bath for 4 hours during which 2.0 g of methylmercaptan was collected in a dry ice bath connected to the reaction flask through a water cooled reflux condenser. The reaction mixture was then evaporated at 15 mm pressure to a solid residue which was then dissolved in 80 ml of 50/50 methanol-ethanol. The solution was filtered and evaporated to approximately 50 ml volume and allowed to cool and crystallize, giving a crop melting at 213.5°C to 215°C of 1,4-dioxaspiro[4.5]decan-2-ylmethyl)-guanidine sulfate.

Therapeutic Function

Antihypertensive

Synthesis

Guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine (12.3.8), is synthesized when cyclohexanone undergoes ketalization by 3-chloro-1,2-proandiol, forming 2- chloromethyl-1,4-dioxyspiro[4,5]decane (12.3.5), which is further akylated by sodium phthalimide. After alkyline hydrazinolysis, the resulting phthalimide derivative (12.3.6) is transformed into 2-aminomethyl-1,4-dioxyspiro[4,5]decane (12.3.7), which is reacted with S-methylthiourea, giving the desired guanadrel (12.3.8) [80–82].

InChI:InChI=1/C10H19N3O2/c11-9(12)13-6-8-7-14-10(15-8)4-2-1-3-5-10/h8H,1-7H2,(H4,11,12,13)

Upstream product

• 108-94-1 cyclohexanone 
• 247226-17-1 N-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)acetamide 
• 45982-66-9 1,4-Dioxaspiro[4,5]dec-2-ylmethanamine 
• 374535-64-5 1,4-dioxa-spiro[4.5]dec-2-ylmethyl-cyanamide 
• 247226-18-2 N-(1,4-Dioxaspiro[4,5]dec-2-ylmethyl)-N',N''-bis(benzyloxycarbonyl)guanidine 

Relevant articles and documents

COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE

To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.

N-Hydroxyl derivatives of guanidine based drugs as enzymatic NO donors

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H2O2. These compounds also displayed vasodilatory activity. Elsevier Science Ltd. All rights reserved.

Synthesis of biologically important guanidine-containing molecules using triflyl-diurethane protected guanidines

The guanidine-containing biologically important molecules, guanadrel, guanoxan, guanethidine and smimovine have been synthesized using the recently developed triflyl-diurethane protected guanidines.