103745-39-7

Basic information

• Product Name: FASUDIL
• Synonyms: FASUDIL;1-(5-ISOQUINOLINE-SULFONYL)-HOMOPIPERAZINE;at877;hexahydro-1-(5-isoquinolinylsulfonyl)-1h-4-diazepine;HA-1077 DIHYDROCHLORIDE NOVEL VASODILATO R AGE;HA 1077, DIHYDROCHLORIDE, 99+%;Hexahydro-1-(5-isoquinolinylsulfonyl)-1H-1,4-diazepine;HA-1077：Eril
• CAS NO: 103745-39-7
• Molecular Formula: C₁₄H₁₇N₃O₂S
• Molecular Weight: 291.37
• EINECS: 1308068-626-2
• Product Categories: Protein Kinase Inhibitors and Activators;Protein Kinase;Signalling;Angiogenesis and Metastasis;Intracellular signaling;APIs;ERIL;Fasudil ada@tuskwei.com sky;18031153937@189.cn;Glutaraldehyde ada@tuskwei.com whatsapp;8618031153937
• Mol File: 103745-39-7.mol

Chemical Properties

• Boiling Point: 506.2 °C at 760 mmHg
• Flash Point: 259.9 °C
• Appearance: white/solid
• Density: 1.289 g/cm³
• Vapor Pressure: 2.55E-12mmHg at 25°C
• Storage Temp.: Store at RT
• Solubility: H2O: >200 mg/mL
• PKA: 9.73±0.20(Predicted)
• Water Solubility: Soluble in water or DMSO
• CAS DataBase Reference: FASUDIL(CAS DataBase Reference)
• NIST Chemistry Reference: FASUDIL(103745-39-7)
• EPA Substance Registry System: FASUDIL(103745-39-7)

Safety Data

• WGK Germany: 3
• RTECS: HM4031166
• Hazardous Substances Data: 103745-39-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Fasudil is used as a vasodilator for cerebral arteries, helping to improve blood flow and reduce the risk of stroke or other vascular issues. It acts as a potent calcium antagonist vasodilator, inhibiting calcium ionophore A23187-induced contraction in arterial strips and phenylephrine-induced contraction in calcium-free media, suggesting its site of action is in the intracellular space.
Used in Hepatitis Treatment:
Fasudil is used as a protein kinase A inhibitor and may be used in medicinal combinations for hepatitis treatment, providing a potential therapeutic option for patients suffering from this condition.
Used in Cell Culture and Research:
Fasudil is used to prevent apoptosis and enhance the survival and cloning efficiency of dissociated human embryonic stem cells (hES cells) without affecting their pluripotency, making it a valuable tool in stem cell research and development.
Used in Drug Delivery Systems:
Fasudil's properties as a calcium antagonist and vasodilator make it a potential candidate for drug delivery systems, particularly in the development of novel therapies for various medical conditions.

Biological Activity

Cyclic nucleotide-dependent protein kinase inhibitor and Rho-associated kinase inhibitor (IC50 = 10.7 μM). Ca2+ antagonist and vasodilator. Also inhibits proliferation of vascular smooth muscle cells.

Biochem/physiol Actions

Cell permeable: yes

in vitro

the inhibitory effects of fasudil on contractile responses to various agonists were examined on strips of rabbit aorta. the concentration-response curves to 5-hydroxytryptamine, prostaglandin f2alpha, histamine, angiotensin ii, noradrenaline and dopamine were concentration-dependently shifted to the right in the presence of fasudil [1].

in vivo

intra-coronary administration of fasudil to dog dose-dependently increased coronary blood flow, with no effect on mean blood pressure or heart rate. intra-coronary infusion of atropine, diphenhydramine or propranolol did not modify the in vivo coronary vasodilator response to fasudil [1].

references

[1] asano t, suzuki t, tsuchiya m, satoh s, ikegaki i, shibuya m, suzuki y, hidaka h. vasodilator actions of ha1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase. br j pharmacol. 1989 dec;98(4):1091-100.[2] zhao j, zhou d, guo j, ren z, zhou l, wang s, zhang y, xu b, zhao k, wang r, mao y, xu b, zhang x; fasudil aneurysmal subarachnoid hemorrhage study group. efficacy and safety of fasudil in patients with subarachnoid hemorrhage: final results of a randomized trial of fasudil versus nimodipine. neurol med chir (tokyo). 2011;51(10):679-83.

InChI:InChI=1/C14H17N3O2S.2ClH/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;2*1H

Upstream product

• 505-66-8 1,4-Diazacycloheptane 
• 105627-79-0 isoquinoline-5-sulfonyl chloride hydrochloride 
• 27655-40-9 isoquinoline-5-sulfonic acid 
• 105628-07-7 fasudil hydrochloride 
• 84468-15-5 5-isoquinolinesulfonyl chloride 

Downstream Products

• 1415682-32-4 C₂₀H₂₁N₃O₂S 
• 105628-07-7 fasudil hydrochloride 
• 141543-79-5 [4-(Isoquinoline-5-sulfonyl)-[1,4]diazepan-1-yl]-phenyl-methanone; hydrochloride 

Relevant articles and documents

Synthesis and biological activity evaluation of novel fasudil derivatives

A series of isoquinoline Rho kinase inhibitors were designed and synthesized based on the ligand-binding pocket model with fasudil as the lead compound. Their biological activity including Rho kinsase inhibitory activity, cell viability were systematically evaluated on (3-[4,5-dimethyltyhiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) assay and lactate deyhydrogenase (LDH) assay. Among these analogues, compounds 2, 3 and 6 not only exhibited Rho kinase inhibitory activity, but also promoted better cell viability. Therefore, they are potential candidates for the future drug discovery. Keywords: (3-[4,5-Dimethyltyhiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) assay and lactate deyhydrogenase (LDH) assay.

Design, Synthesis, and Biological Evaluations of Several Fasudil Analogues

In our previous work, (S)-6H-1-(5-isoquinolinesulfonyl)-2-hydroxymethyl-1-pyrrolidine and (S)-6H-1-(5-isoquinolinesulfonyl)-2-chloromethyl-1-pyrrolidine displayed potent inhibitory activity. Therefore, with these two substances as lead compounds, we designed and synthesized their enantiomers to reveal the inhibitory effects of chirality on Rho kinase. It is found that their enantiomers exhibited much better Rho kinase inhibitory activity and strongly promoted synapse formation. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. With added antigens, the changes from C57BL/6 mice's limbs and tail was observed and scored by clinical evaluation. The synthetic compounds may simultaneously reduce symptoms of experimental autoimmune encephalomyelitis and inhibit inflammatory infiltration of the central nervous system. Thus, these compounds may be potential candidates for inhibition of Rho kinase and should be considered for further experimental study in relation to multiple sclerosis.

Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis

Hybrid compounds containing structural fragments of the Rho kinase inhibitor fasudil and the NRF2 inducers caffeic and ferulic acids were designed with the aid of docking and molecular mechanics studies. Following the synthesis of the compounds using a peptide-coupling methodology, they were characterized for their ROCK2 inhibition, radical scavenging, effects on cell viability (MTT assay), and NRF2 induction (luciferase assay). One of the compounds (1d) was selected in view of its good multitarget profile and good tolerability. It was able to induce the NRF2 signature, promoting the expression of the antioxidant response enzymes HO-1 and NQO1, via a KEAP1-dependent mechanism. Analysis of mRNA and protein levels of the NRF2 pathway showed that 1d induced the NRF2 signature in control and SOD1-ALS lymphoblasts but not in sALS, where it was already increased in the basal state. These results show the therapeutic potential of this compound, especially for ALS patients with a SOD1 mutation.

Preparation method of Fasudil hydrochloride

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.

Refining method of Fasudil hydrochloride

The invention discloses a synthetic refining method of Fasudil hydrochloride. The method includes: taking 5-isoquinolinesulfonic acid as the raw material, adopting DMF as the catalyst, using thionyl chloride as the chlorinating agent and solvent, conducting reflux concentration, then performing dichloromethane pulping to obtain isoquinoline-5-sulfonyl chloride hydrochloride, conducting neutralization and extraction to obtain a dichloromethane solution of isoquinoline-5-sulphonyl chloride, adding the dichloromethane solution of isoquinoline-5-sulphonyl chloride dropwise into a dichloromethane solution of homopiperazine, carrying out low temperature reaction to obtain 1-(5-isoquinoline sulfonyl)homopiperazine, adding dilute hydrochloric acid dropwise into the reaction solution, performing cooling to precipitate a solid Fasudil hydrochloride crude product 1, neutralizing the aqueous solution of the crude product 1, then conducting dichloromethane extraction, using an HCl-ethanol solutionto adjust acid to obtain a Fasudil hydrochloride crude product 2, and carrying out ethanol aqueous solution refining and drying so as to obtain a high purity final product meeting the requirements. The method provided by the invention can remove thionyl chloride in large quantities, facilitates subsequent operation and enlarged production, also precipitates the Fasudil hydrochloride crude product1 in a two-phase solvent directly by cooling, and can remove a large number of pigment impurities.

Isoquinoline derivative as well as preparation method and application thereof

The invention relates to an isoquinoline derivative expressed by a general formula (I) or pharmaceutically acceptable salts thereof, wherein Y represents for carbonyl or sulfonyl. The invention also relates to a preparation method of the compound and application to preparation of medicines for treating NK/T cell malignant tumor. The formula is as shown in the description.

THERAPEUTIC AGENT FOR OCULAR FUNDUS DISEASE

Disclosed herein is a prophylactic or therapeutic agent for ocular fundus disease, especially diabetic retinopathy or age-related macular degeneration. The prophylactic or therapeutic agent for ocular fundus disease comprising: (S)-(?)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine, a salt thereof, or a solvate thereof, as an active ingredient.

FASUDIL-CONTAINING PREPARATION AND METHOD OF IMPROVING STABILITY THEREOF

Fasudil-containing preparations that despite the use of a container excelling in the visibility of contents without particularly blocking of light, exhibit high stability against light; and a method of improving the stability of the preparations against light, or storing the same. By regulating the pH value of aqueous solution of fasudil charged in a colorless transparent container to ≦ 5.5, there can be provided fasudil-containing preparations excelling in stability against light; and can be provided a method of improving the stability of the aqueous solution of fasudil against light, or storing the same.

1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride hydrates

Disclosed is a 1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride hydrate having a water content of from 2.5 to 15.5% by weight represented by the following formula (I): STR1 wherein n means a number in the range of from 1/2 to 3. Since the 1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride hydrate of the present invention has excellent shapeability as compared to a 1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride anhydride, a tablet having satisfactory hardness can be obtained even with a relatively low compression pressure in a tableting process. Further, due to a reduction in the compression pressure needed for tableting, various advantages are brought about, such as improved disintegratability of the resultant tablet when the tablet is orally taken, so that good dissolution of 1-(5-isoquinolinesulfonyl)homopiperazine hydrochloride from the tablet can be achieved, as well as suppression of abrasion of the die and punch used in producing tablets by compression, and the like.