105628-07-7 Usage
Description
Fasudil hydrochloride, also known as Fasudil monohydrochloride, is a novel calcium antagonistic vasodilator that was marketed for the treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). It is a potent inhibitor of myosin light chain kinase and protein kinase C, and it serves as a selective Rho-associated protein kinase (ROCK) inhibitor. Fasudil hydrochloride is used in the prevention and treatment of cardiovascular and cerebrovascular diseases, as well as in the inhibition of proliferation of vascular smooth muscle cells. It has an intracellular mode of action in relaxing vascular smooth muscle, which makes it distinct from other calcium channel blockers. Additionally, it protects against methyl mercury-induced axonal degeneration.
Uses
Used in Cardiovascular and Cerebrovascular Applications:
Fasudil hydrochloride is used as a vasodilator for the prevention and treatment of cardiovascular and cerebrovascular diseases. It acts as a potent Rho-kinase inhibitor, which helps in the inhibition of proliferation of vascular smooth muscle cells.
Used in Cerebral Vasospasm Treatment:
Fasudil hydrochloride is used as a treatment for cerebral vasospasm following subarachnoid hemorrhage (SAH). It helps in decreasing the occurrence of angiographic severe and symptomatic vasospasm and cerebral infarction without decreasing systemic blood pressure.
Used in Neurological Deficits:
Fasudil hydrochloride is used as a treatment for patients with neurological deficits due to vasospasm, providing relief and improving their condition.
Used in Clinical Trials:
Fasudil hydrochloride is reportedly in clinical trials for acute ischemic stroke, sequelae of cerebral vascular diseases, and angina pectoris, indicating its potential in treating a range of conditions related to blood flow and vascular health.
Brand Name:
Eril is the brand name under which Fasudil hydrochloride is marketed.
Indications and Usage
Fasudil Hydrochloride is a new drug with a wide range of pharmacological effects, developed by Asahi Kasei Corporation (Japan.) It is a cardiovascular and cerebrovascular drug which improves symptoms of ischemic cerebrovascular disease such as cerebral vasospasm following subarachnoid hemorrhage. It has significant neuroprotective and therapeutic effects for ischemic cerebrovascular disease, and is suited for clinical use, particularly at the grassroots level to reduce mortality and improve quality of life.
Mechanisms of Action
Fasudil Hydrochloride is an isoquinoline sulfonamide derivative which can relax separated cerebral blood vessels, inhibit the shrinkage of separated blood vessels caused by calcium influx, inhibit different mechanisms of brain blood vessel contraction from contractile agents, and inhibit intracellular calcium ion activity without reducing calcium ion concentration. Fasudil Hydrochloride is an RHO kinase inhibitor which dilates vessels, reduces tension of endothelial cells, and improves microcirculation of brain tissue without producing or exacerbating diversion of blood to the brain, by increasing activity of myosin light chain phosphatase. At the same time, it can protect nerves against apoptosis and promote their regeneration. Fasudil Hydrochloride promotes recovery of neural function and reduces clinical symptoms.
Adverse reactions
Adverse reactions after use can include intracranial hemorrhage, gastrointestinal bleeding, pulmonary hemorrhage, nasal bleeding, subcutaneous bleeding, and loss of consciousness, etc., as well as abnormal liver function. Low blood pressure, anemia, leukopenia, renal dysfunction, polyuria, rashes, and fever, etc. occur occasionally.
Warnings and Precautions
Patients with intracranial hemorrhage or possibility thereof, or low blood pressure, should not use. Patients with diabetes mellitus, cerebral arterial sclerosis, severe disturbance of consciousness, subarachnoid hemorrhages with cerebrovascular disorders, and liver or kidney dysfunction, or those over 70 years old, pregnant, or children should use with caution. Breastfeeding women should stop while using the drug. Fasudil Hydrochloride can only be administered via intravenous drip.
Originator
Asahi Chemical (Japan)
References
1) Davies et al. (2000), Specificity and mechanism of action of some commonly used protein kinase inhibitors; Biochem. J., 351 95
2) Anwar et al. (2013), Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed; Vascul. Pharmacol., 58 140
3) Jiang et al. (2012), Fasudil, a rho-kinase inhibitor, attenuates bleomycin-induced pulmonary fibrosis in mice; Int. J. Mol. Sci., 13 8293
Check Digit Verification of cas no
The CAS Registry Mumber 105628-07-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,5,6,2 and 8 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 105628-07:
(8*1)+(7*0)+(6*5)+(5*6)+(4*2)+(3*8)+(2*0)+(1*7)=107
107 % 10 = 7
So 105628-07-7 is a valid CAS Registry Number.
InChI:InChI=1/C14H17N3O2S.ClH/c18-20(19,17-9-2-6-15-8-10-17)14-4-1-3-12-11-16-7-5-13(12)14;/h1,3-5,7,11,15H,2,6,8-10H2;1H
105628-07-7Relevant articles and documents
Unconventional Synthetic Process of Fasudil Hydrochloride: Costly Homopiperazine Was Avoided
Niu, Jinming,Wang, Dingding,Wu, Weiting,Yang, Wu-Lin,Zhao, Jianhong
, (2021/12/06)
An efficient, robust, and cost-effective synthetic process of fasudil hydrochloride 1 was developed. Starting from readily available ethylenediamine and 5-isoquinoline sulfonyl chloride, the target product 1 was prepared through a six-step reaction, including sulfonamidation, protection, nucleophilic substitution, deprotection, cyclization, and salification. The process afforded 1 in 67.1% overall yield (based on 5-isoquinoline sulfonyl chloride) with 99.94% purity. Compared to the earlier published methodologies, the use of homopiperazine or its derivatives as intermediates was avoided. The salient features of this environmentally friendly synthetic route include easily available starting materials and operational simplicity, which could be suitable for large-scale industrial production.
Preparation method of fasudil hydrochloride
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Paragraph 0032-0049, (2020/07/13)
The invention belongs to the technical field of medicines, and relates to a preparation method of fasudil hydrochloride. The specific process of the method comprises the following steps: firstly reacting isoquinoline-5-sulfonic acid with 2-chloro-4, 6-dimethoxy-1, 3, 5-triazine in an organic solvent under the action of organic alkali, then reacting the obtained reaction product with homopiperazine, washing the obtained reaction product with water, washing the obtained reaction product with alkali, and salifying and recrystallizing the obtained reaction product to obtain the high-purity fasudilhydrochloride. The impurity content of the fasudil hydrochloride prepared by the method is lower than 0.1%, and the purity of the fasudil hydrochloride reaches 99.5% or above. The preparation methodcompletely avoids the problem of product pigments caused by acyl chloride corrosion and hydrolysis, has the advantages of safety, environmental protection, low production cost, high product quality, convenience in operation and the like, and is suitable for industrial production.
Method for purifying fasudil hydrochloride
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Page/Page column 4-6, (2019/05/15)
The invention provides a method for purifying fasudil hydrochloride. According to the method, diffluent fasudil hydrochloride is converted into slightly soluble fasudil dihydrogen phosphate in a water-methanol solution, so that high-content piperazine impurities, most pigment and other water-soluble impurities which are easily dissolved in water and methanol are removed. The method has controllable process parameters, convenient operation and a mild reaction.