Ripasudil

Base Information

• Chemical Name: Ripasudil
• CAS No.: 223645-67-8
• Molecular Formula: C15H18FN3O2S
• Molecular Weight: 323.39
• UNII: 11978226XX
• DSSTox Substance ID: DTXSID001025609
• Nikkaji Number: J3.122.028I
• Wikipedia: Ripasudil
• Wikidata: Q21098890
• NCI Thesaurus Code: C152226
• Pharos Ligand ID: 6CRF1W92FPCB
• Metabolomics Workbench ID: 154015
• ChEMBL ID: CHEMBL3426621
• Mol file: 223645-67-8.mol

Synonyms:Glanatec;K-115;K115 compound;ripasudil

Chemical Property of Ripasudil

Chemical Property:

• Boiling Point: 497.2±55.0 °C(Predicted)
• PKA: 9.70±0.40(Predicted)
• PSA: 70.68000
• Density: 1.293±0.06 g/cm3(Predicted)
• LogP: 3.09390
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• XLogP3: 1.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 323.11037616
• Heavy Atom Count: 22
• Complexity: 482

Purity/Quality:

97% ^*data from raw suppliers

K-115 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)F
• Isomeric SMILES: C[C@H]1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)F
• Recent ClinicalTrials: A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops After Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
• Recent EU Clinical Trials: A Double-Masked, Randomized, Placebo-Controlled, Parallel-Group, 12-Week Administration With Two-Week Gradual Dose Taper Phase and
• Recent NIPH Clinical Trials: Study for intraocular pressure elevation after glaucoma surgery
• Description: Ripasudil (Glanatec TM, Kowa Pharmaceutical), a close derivative of fasudil, is another Rho kinase inhibitor approved in Japan at the end of 2014 for the treatment of glaucoma and ocular hypertensionwhen other therapeutic agents are not effective or cannot be administered. Additionally, ripasudil has been tested in diabetic retinopathy clinical trials and shown to promote corneal endothelial cell proliferation, endothelium regeneration, and wound healing.

Technology Process of Ripasudil

There total 16 articles about Ripasudil which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.3%

(S)-tert-butyl 4-[(4-fluoroisoquinoline-5-yl)sulfonyl]-3-methyl-1,4-diazepane-1-carboxylate (1360538-86-8) → ripasudil (223645-67-8)

Guidance literature:

With hydrogenchloride; In ethyl acetate; for 2h; Inert atmosphere; Cooling with ice; Large scale;

Reference yield:

4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline hydrochloride (223644-02-8) → ripasudil (223645-67-8)

Guidance literature:

With sodium hydroxide; sodium dihydrogenphosphate; pH=6.0;

Reference yield:

(S)-6-benzyloxycarbonylamino-4-(tert-butoxycarbonyl)-4-azaheptan-1-ol (913625-37-3) → ripasudil (223645-67-8)

Guidance literature:

Multi-step reaction with 5 steps

1: triethylamine / dichloromethane / 16 h / 0 - 20 °C

2: sodium hydride / dimethyl sulfoxide; mineral oil / 2 h / 20 - 25 °C

3: palladium 10% on activated carbon; hydrogen / mineral oil; methanol / 19 h / 20 °C / Inert atmosphere

4: triethylamine / acetonitrile / 2 h / Inert atmosphere; Cooling with ice; Large scale

5: hydrogenchloride / ethyl acetate / 2 h / Inert atmosphere; Cooling with ice; Large scale

With hydrogenchloride; palladium 10% on activated carbon; hydrogen; sodium hydride; triethylamine; In methanol; dichloromethane; dimethyl sulfoxide; ethyl acetate; acetonitrile; mineral oil;

upstream raw materials:

4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline hydrochloride

(S)-4-fluoro-N-[1-(3-hydroxypropylamino)propan-2-yl]isoquinoline-5-sulfonamide

(S)-6-benzyloxycarbonylamino-4-(tert-butoxycarbonyl)-4-azaheptan-1-ol

(S)-6-benzyloxycarbonylamino-4-(tert-butoxycarbonyl)-4-azaheptyl methanesulfonate

Downstream raw materials:

4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline hydrochloride