223644-02-8

Usage

Uses

Used in Pharmaceutical Industry:
Ripasudil Hydrochloride is used as a therapeutic agent for the treatment of glaucoma and ocular hypertension. It is particularly effective when other therapeutic agents are not effective or cannot be administered, making it a valuable alternative for patients.
Application Reason:
The compound works by inhibiting Rho kinase, which plays a role in increasing the resistance of the trabecular meshwork to aqueous humor outflow. This inhibition helps to lower the intraocular pressure, providing relief from the symptoms of glaucoma and ocular hypertension.
Additionally, Ripasudil Hydrochloride has been tested in clinical trials for diabetic retinopathy, where it has shown potential in promoting corneal endothelial cell proliferation, endothelium regeneration, and wound healing. This suggests that the compound may have broader applications within the field of ophthalmology and could potentially benefit patients with other eye conditions related to impaired healing or cell regeneration.

Upstream product

• 223645-67-8 ripasudil 
• 1360538-86-8 (S)-tert-butyl 4-[(4-fluoroisoquinoline-5-yl)sulfonyl]-3-methyl-1,4-diazepane-1-carboxylate 
• 906820-08-4 4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride 
• 194032-32-1 tert-butyl (S)-3-methyl-1,4-diazepane-1-carboxylate 
• 906820-09-5 4-fluoroisoquinoline sulfate 
• 223644-12-0 (S)-(-)-4-fluoro-N-(1-hydroxypropan-2-yl)isoquinoline-5-sulfonamide 
• 394-67-2 4--fluoroisoquinoline 

Downstream Products

• 223645-67-8 ripasudil 

Relevant academic research and scientific papers

Method for preparing isoquinoline hydrochloride intermediate and Rho kinase inhibitor by using BTC/Ph3PO chlorination system

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.

Refinement method of (s)-4-[(4-fluoroisoquinolyl-5-yl)sulfonyl]-3-methyl-1,4-diazacycloheptane hydrochloride

The invention discloses a refinement method of (s)-4-[(4-fluoroisoquinolyl-5-yl)sulfonyl]-3-methyl-1,4-diazacycloheptane hydrochloride. The method comprises the following steps: adding a (s)-4-[(4-fluoroisoquinolyl-5-yl)sulfonyl]-3-methyl-1,4-diazacycloheptane hydrochloride crude product into a mixed solvent composed of ethanol and acetonitrile, carrying out heating under reflux until the (s)-4-[(4-fluoroisoquinolyl-5-yl)sulfonyl]-3-methyl-1,4-diazacycloheptane hydrochloride crude product is completely dissolved, carrying out stirring and cooling to crystallize, and carrying out filtering and drying to obtain the refined product. The method obviously enhances the liquid-phase purity and effective component content of the product, so that the purity of the refined product reaches 99.85% or above, and the content of any individual impurity is less than 0.1%. The method is also convenient for large-scale production of the product, and is convenient to operate and lower in cost.

A Practical synthesis of novel Rho-kinase inhibitor, (S)-4-fluoro-5-(2- methyl-1,4-diazepan-1-ylsulfonyl)-isoquinoline

A practical synthesis of novel Rho-kinase inhibitor, (S)-4-fluoro-5- (2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline hydrochloride dihydrate (1) was achieved in a pilot-scale production. We have demonstrated the regioselective chlorosulfonylation of 4-fluoroisoquinoline in an one-pot reaction to afford 4-fluoroisoquinoline-5-sulfonyl chloride and the asymmetric construction of the (S)-2-methyl-1,4-diazepane moiety as key steps. The Japan Institute of Heterocyclic Chemistry.

(S)-(-)-1-(4-FLUOROISOQUINOLIN-5-YL)SULFONYL-2-METHYL-1,4-HOMOPIPERAZINE HYDROCHLORIDE DIHYDRATE

(S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride dihydrate; a process for producing the dihydrate; and a medicinal composition containing the dihydrate. This compound has lower hygroscopicity than anhydrous crystals of (S)-(-)-1-(4-fluoroisoquinolin-5-yl)sulfonyl-2-methyl-1,4-homopiperazine hydrochloride and is superior in chemical stability. It is hence useful as a medicine.