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
• Article Data: 11

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

Chemical Properties

White Crystalline Solid

Uses

Different sources of media describe the Uses of 103745-39-7 differently. You can refer to the following data:
1. vasodilator (cerebral), Ca antagonist
2. A potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits (1) calcium ionophore A23187 induced co ntraction in arterial strips and (2) phenylephrine induced contraction in calcium free media suggesting that its site of action is in the intracellular space. Also reported to potently inhibit Rho- associated Kinase (ROCK IC50= 10.7 uM).
3. Fasudil is a protein kinase A inhibitor and may be used in medicinal combinations for hepatitis treatment.

General Description

A cell-permeable, reversible, and ATP-competitive Ca2+ antagonist with anti-vasospastic properties. Inhibits protein kinase A (Ki = 1.6 μM), protein kinase G (Ki = 1.6 μM), and myosin light chain kinase (Ki = 3.6 μM). Also reported to potently inhibit Rho-associated kinase (ROCK; IC50 = 10.7 μM). Prevents apoptosis and enhances the survival and cloning efficiency of dissociated hES cells without affecting their pluripotency.

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 
• 105628-07-7 fasudil hydrochloride 
• 27655-40-9 isoquinoline-5-sulfonic acid 
• 84468-15-5 5-isoquinolinesulfonyl chloride 

Downstream Products

• 105628-07-7 fasudil hydrochloride 
• 1415682-32-4 C₂₀H₂₁N₃O₂S 
• 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.

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.

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.