105628-07-7 Usage
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.
Description
Fasudil hydrochloride, a novel calcium antagonistic vasodilator, was marketed
for the treatment of cerebral vasospasm following subarachnoid hemorrhage
(SAH). Fasudil is also a potent inhibitor of myosin light chain kinase and protein kinase
C. In contrast to other calcium channel blockers, which regulate the influx of calcium
ions through the cell membrane but not involved in the intracellular regulatory
mechanism of the calcium, fasudil was suggested to have an intracellular mode of
action in relaxing vascular smooth muscle. In patients with neurological deficits due to
vasospasm, fasudil decreased the occurrence of angiographic severe and
symptomatic vasospasm and cerebral infarction without decreasing systemic blood
pressure. Fasudil is reportedly in clinical trials for acute ischemic stroke, sequelae of
cerebral vascular diseases and angina pectoris.
Originator
Asahi Chemical (Japan)
Uses
Different sources of media describe the Uses of 105628-07-7 differently. You can refer to the following data:
1. Fasudil monohydrochloride is used in the prevention and treating cardiovascular and cerebrovascular diseases. It is also used in the inhibition of proliferation of vascular smooth muscle cells. It serves as a selective Rho-associated protein kinase (ROCK) inhibitor. Further, it protects against methyl mercury-induced axonal degeneration.
2. vasodilator, potent Rho-kinase inhibitor
Brand name
Eril
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.
Method for preparing isoquinoline hydrochloride intermediate and Rho kinase inhibitor by using BTC/Ph3PO chlorination system
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Paragraph 0112-0127, (2020/11/23)
The invention discloses a method for preparing an isoquinoline hydrochloride intermediate and an Rho kinase inhibitor by using a BTC/Ph3PO chlorination system, which comprises the following steps: putting an isoquinoline 5-sulfonic acid compound, BTC and a catalytic amount of Ph3PO into a reaction bottle, adding an organic solvent A, uniformly mixing all the components, and heating the mixture toreact; after the reaction is finished, carrying out suction filtration and drying to obtain a white solid isoquinoline hydrochloride intermediate, which is the isoquinoline 5-sulfonylchloride hydrochloride compound; concentrating a mother liquor part of the filtrate for separating out Ph3PO at a low temperature, and washing Ph3PO with a low-polarity solvent for recycling use. The method has the advantages of few side reactions, high product quality, less three-waste pollution, high atom economy and the like, the invention also provides a method for further preparing the Rho kinase inhibitor byutilizing the prepared isoquinoline hydrochloride intermediate; the impurities in the Rho kinase inhibitor prepared by the method are obviously lower than those in medicines obtained by a traditionalmethod.
Preparation method of Fasudil hydrochloride
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Paragraph 0032; 0036; 0042; 0043; 0048; 0049; 0053; 0054, (2019/04/17)
The invention belongs to the technical field of preparation of heterocyclic compounds, and particularly relates to a preparation method of Fasudil hydrochloride. The preparation method includes the following steps: 1) reacting isoquinoline-5-sulfonyl chloride hydrochloride, homopiperazine and liquid ammonia in an organic solvent at the temperature of 10-15 DEG C for 2-4 hours, subjecting a reactedreaction system to water extraction separation, and concentrating an oil-phase separation product to obtain an intermediate; 2) subjecting the intermediate obtained in the step 1) and hydrochloric acid to a salt formation reaction to obtain the Fasudil hydrochloride. The preparation method has the advantages that the isoquinoline-5-sulfonyl chloride hydrochloride as a raw material directly reactswith the homopiperazine to obtain the intermediate, so that the operation steps are reduced and the preparation process is simple.
