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Chemistry

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Also known as: 223645-67-8, K-115 free base, K115 free base, Ripasudil [inn], Ripasudil free base, K-115 (free base)
Molecular Formula
C15H18FN3O2S
Molecular Weight
323.4  g/mol
InChI Key
QSKQVZWVLOIIEV-NSHDSACASA-N
FDA UNII
11978226XX

Ripasudil
Ripasudil, as hydrochloride hydrate (K-115), is a specifc Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor used for the treatment of glaucoma and ocular hypertension. It was first approved for treatment in Japan in September 2014. This medication is available in the form of a 0.4% eye drop solution under the brand name Glanatec. Ripasudil is a well tolerated medication that is used when other drugs have been proven to be non-effective or cannot be administered.
1 2D Structure

Ripasudil

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
4-fluoro-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline
2.1.2 InChI
InChI=1S/C15H18FN3O2S/c1-11-8-17-6-3-7-19(11)22(20,21)14-5-2-4-12-9-18-10-13(16)15(12)14/h2,4-5,9-11,17H,3,6-8H2,1H3/t11-/m0/s1
2.1.3 InChI Key
QSKQVZWVLOIIEV-NSHDSACASA-N
2.1.4 Canonical SMILES
CC1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)F
2.1.5 Isomeric SMILES
C[C@H]1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)F
2.2 Other Identifiers
2.2.1 UNII
11978226XX
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Glanatec

2. K-115

3. K115 Compound

2.3.2 Depositor-Supplied Synonyms

1. 223645-67-8

2. K-115 Free Base

3. K115 Free Base

4. Ripasudil [inn]

5. Ripasudil Free Base

6. K-115 (free Base)

7. Chembl3426621

8. 4-fluoro-5-[[(2s)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline

9. 11978226xx

10. (s)-4-fluoro-5-((2-methyl-1,4-diazepan-1-yl)sulfonyl)isoquinoline

11. 1h-1,4-diazepine, 1-((4-fluoro-5-isoquinolinyl)sulfonyl)hexahydro-2-methyl-, (2s)-

12. Isoquinoline, 4-fluoro-5-(((2s)-hexahydro-2-methyl-1h-1,4-diazepin-1-yl)sulfonyl)-

13. Unii-11978226xx

14. K 115 Free Base

15. Ripasudil [mi]

16. Ripasudil [who-dd]

17. Schembl31542

18. Gtpl10423

19. Chebi:136046

20. Dtxsid001025609

21. Bcp11083

22. Ex-a3647

23. Zinc3940873

24. Bdbm50087135

25. Hy-15685a

26. Mfcd28291829

27. Nsc800869

28. Cs-3402

29. Db13165

30. Nsc-800869

31. Ncgc00496843-01

32. Ac-36873

33. As-35170

34. K-115 (ripasudil Hydrochloride Dihydrate)

35. Q21098890

36. (s)-(-)-1-(4-fluoro-5-isoquinolinesulfonyl)-2-methyl-1,4-homopiperazine

37. 4-fluoro-5-[[(2s)-2beta-methylhexahydro-1h-1,4-diazepine-1-yl]sulfonyl]isoquinoline

2.4 Create Date
2006-10-25
3 Chemical and Physical Properties
Molecular Weight 323.4 g/mol
Molecular Formula C15H18FN3O2S
XLogP31.5
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count6
Rotatable Bond Count2
Exact Mass323.11037616 g/mol
Monoisotopic Mass323.11037616 g/mol
Topological Polar Surface Area70.7 Ų
Heavy Atom Count22
Formal Charge0
Complexity482
Isotope Atom Count0
Defined Atom Stereocenter Count1
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Ripasudil has been proven to be effective in the twice daily treatment of glaucoma and ocular hypertension. It is currently in studies to be approved for both diabetic retinopathy and diabetic macular oedema.


Treatment of corneal dystrophy


5 Pharmacology and Biochemistry
5.1 Pharmacology

Ripasudil has high intraocular permeability and works by decreasing intraocular pressure (IOP) in a dose-dependent manner and increasing flow facility. The maximum reduction of IOP occurs after 1 to 2 hours.


5.2 ATC Code

S - Sensory organs

S01 - Ophthalmologicals

S01E - Antiglaucoma preparations and miotics

S01EX - Other antiglaucoma preparations

S01EX07 - Ripasudil


5.3 Absorption, Distribution and Excretion

Route of Elimination

Riapsudil is cleared by the kidneys at a rate of 7.112L/h.


Clearance

Ripasudil has a renal clearance of 7.112 L/h.


5.4 Biological Half-Life

The half life of Ripasudil is 0.455 hrs.


5.5 Mechanism of Action

Ripasudil is a highly selective and potent Rho-associated coiled/coil-containing kinase protein (ROCK) inhibitor. Rho-kinase (ROCK) is an effector protein of Rho which binds with Rho to form a Rho/Rho-kinase complex. This complex then regulates many physiological functions including smooth muscle contractions, chemotaxis, neural growth and gene expression. ROCK comes in 2 isoforms: ROCK-1 and ROCK-2 and these two isoforms are distributed widely in our tissues including ocular tissues such as the iris, retina, trabecular meshwork and ciliary muscles. Atypical regulation of ROCK levels is involved in the pathogenesis of diseases such as glaucoma, ocular hypertension, cataracts and other retinal disorders. Ripasudil acts as very highly selective and potent inhibitor with an IC50 of Ripasudil with ROCK-1 of 0.051 umol/L and with ROCK-2 of 0.019 umol/L. ROCK inhibitors have efficacy in reducing IOP by acting on the trabecular meshwork in the eye directly to increase conventional outflow through the Schlemms canal. Ripasudil will inhibit ROCK and induce cytoskeletal changes including the retraction and rounding of cell bodies and cause disruption of actin bundles in this trabecular meshwork. This can reduce the compaction of trabecular meshwork tissue and eventually result in increased aqueous outflow in the eye and reduced resistance to fluid flow. Thus, Ripasudil is effective by inducing cytoskeletal changes which are depending on ROCK inhibition. Ripasudil decreases IOP by increasing outflow facility along with modulating the behavior of trabecular meshwork cells and Schlemms canal endothelial (SCE) cell permeability along with a disruption of the tight junction. When Ripasudil is used in combination with prostaglandin analogues it results in increased uveoscleral outflow and when used in combination with beta blockers it results in reduced aqueous production.


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01

FARMAK, a.s

Czech Republic
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Virtual BoothFarmak works in the development, production and marketing of APIs, Intermediates & Specialties// FDA inspected.

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Ripasudil

About the Company : Farmak, A.S. is a privately held chemical and pharmaceutical company based in the Czech Republic. It specializes in researching, developing and producing active pharmaceutical ingr...

Farmak, A.S. is a privately held chemical and pharmaceutical company based in the Czech Republic. It specializes in researching, developing and producing active pharmaceutical ingredients (APIs), intermediates and specialized chemicals. The company primarily focuses on exporting its products, with the main markets being the EU, USA, India, Japan and Latin America. Additionally, Farmak offers contract manufacturing and custom synthesis services through its R&D department to support the clients.
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Virtual BoothJinan Tantu Chemicals offers customized R&D services & production of small molecule APIs & pharmaceutical intermediates.

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Ripasudil

About the Company : Jinan Tantu Chemicals Co., Ltd. operates as a Contract Development and Manufacturing Organization (CDMO) that serves pharmaceutical companies worldwide. Our core services include c...

Jinan Tantu Chemicals Co., Ltd. operates as a Contract Development and Manufacturing Organization (CDMO) that serves pharmaceutical companies worldwide. Our core services include customized R&D as well as the production of small molecule pharmaceutical intermediates and Active Pharmaceutical Ingredients (APIs) for both international and domestic pharmaceutical firms. Our capabilities span from laboratory-scale kilograms to commercial ton-scale production. Additionally, we are committed to independent research and development, as well as the production and sales of high-end pharmaceutical intermediates and API products.
Jinan Tantu Chemicals

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Ripasudil

About the Company : Established in 2011 and situated in Hangzhou, Zhejiang, China, Hangzhou Longshine Bio-Tech CO., Ltd is dedicated to providing services for pharmaceutical and chemical products, cat...

Established in 2011 and situated in Hangzhou, Zhejiang, China, Hangzhou Longshine Bio-Tech CO., Ltd is dedicated to providing services for pharmaceutical and chemical products, catering to both export and import markets. The company consists of two primary business departments: the Professional Sourcing/Product Team and the Quality Team. Backed by experienced partners, Longshine has evolved into a trustworthy supplier of high-quality products and received ISO9001:2008 certification in 2017.
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01-Oct-2022
13-Sep-2024
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ABOUT THIS PAGE

Ripasudil Manufacturers

A Ripasudil manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Ripasudil, including repackagers and relabelers. The FDA regulates Ripasudil manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Ripasudil API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Ripasudil manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Ripasudil Suppliers

A Ripasudil supplier is an individual or a company that provides Ripasudil active pharmaceutical ingredient (API) or Ripasudil finished formulations upon request. The Ripasudil suppliers may include Ripasudil API manufacturers, exporters, distributors and traders.

click here to find a list of Ripasudil suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Ripasudil GMP

Ripasudil Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Ripasudil GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Ripasudil GMP manufacturer or Ripasudil GMP API supplier for your needs.

Ripasudil CoA

A Ripasudil CoA (Certificate of Analysis) is a formal document that attests to Ripasudil's compliance with Ripasudil specifications and serves as a tool for batch-level quality control.

Ripasudil CoA mostly includes findings from lab analyses of a specific batch. For each Ripasudil CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Ripasudil may be tested according to a variety of international standards, such as European Pharmacopoeia (Ripasudil EP), Ripasudil JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Ripasudil USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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