ChemicalBook > CAS DataBase List > Ripasudil hydrochloride dihydrate

Ripasudil hydrochloride dihydrate

Product Name: Ripasudil hydrochloride dihydrate
CAS No.: 887375-67-9
Chemical Name: Ripasudil hydrochloride dihydrate
Synonyms: K-115 HCL;K 115; K115;K115 HCL 2H2O;K-115 (HCl H2O);Ripasudil (K-115);K115 HCl Dihydrate;Ripasudil free base;K 155 HCl dihydrate;RipasudilHCl Hydrate;Ripasudil HCl Dihydrate
CBNumber: CB52667596
Molecular Formula: C15H21ClFN3O3S
Formula Weight: 377.86
MOL File: 887375-67-9.mol

Less

Ripasudil hydrochloride dihydrate Property

storage temp.: Store at -20°C
solubility: insoluble in EtOH; ≥123.2 mg/mL in DMSO; ≥41.7 mg/mL in H2O
form: solid
color: White to off-white
Stability:: Hygroscopic

Less

Safety

Risk Statements: 24/25-26-28
Safety Statements: 28-38-41-48
HS Code: 29339900

Less

Hazard and Precautionary Statements (GHS)

Less

N-Bromosuccinimide Price

TRC

Product number: R517900
Product name: RipasudilHydrochloride
Packaging: 100mg
Price: $1815
Updated: 2021/12/16

Biosynth Carbosynth

Product number: FR162274
Product name: Ripasudil HCl hydrate
Packaging: 2mg
Price: $125
Updated: 2021/12/16

ApexBio Technology

Product number: B4809
Product name: K-115
Packaging: 5mg
Price: $135
Updated: 2021/12/16

ChemScene

Product number: CS-3401
Product name: Ripasudil
Purity: 99.75%
Packaging: 5mg
Price: $192
Updated: 2021/12/16

AK Scientific

Product number: 3757AH
Product name: K-115
Packaging: 5mg
Price: $200
Updated: 2021/12/16

Less

Ripasudil hydrochloride dihydrate Chemical Properties,Usage,Production

Description

Ripasudil hydrochloride hydrate (Glanatec®) was approved in Japan in 2014 for the treatment of glaucoma and ocular hypertension. Originally discovered by D. Western Therapeutics Institute, Inc. and licensed by the Kowa Company, Ltd, ripasudil functions as a selective Rho-kinase inhibitor and reduces intraocular pressure by stimulation of aqueous humour drainage of the trabecular meshwork. While this recent approval allows for use of ripasudil as a twice-daily monotherapy treatment when other drugs cannot be used or are not effective, clinical trials using ripasudil as a combination therapy with other glaucoma drugs have shown promising results in the treatment of primary open-angle glaucoma or ocular hypertension. Currently, the Kowa Company is also pursuing trials focused on the use of ripasudil for the treatment of diabetic retinopathy and diabetic macular edema.

Uses

Ripasudil Hydrochloride Dihydrate is a derivative of fasudil and a rho kinase inhibitor (1,2). It is used for the treatment of glaucoma and ocular hypertension.

Uses

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.

Synthesis

While initial synthetic routes to ripasudil were carried out via a stepwise functionalization of 4-fluoroisoquinoline-5-sulfonyl chloride (238), more recent reports describe an efficient route to ripasudil employing a late stage-coupling of Boc-diazepane (237) with 4-fluoroisoquinoline-5-sulfonyl chloride (238), enabling synthesis on multi-kilogram scale and isolation of the drug in high purity. This optimized route to ripasudil begins with 2-nitrobenzene sulfonyl chloride (NsCl)- mediated protection of (S)-2-amino-1-propanol (234) in 82% yield. In this case, use of the NaHCO3/THF/H2O conditions were essential for preventing bis-nosylation.228 Alcohol activation with methanesulfonyl chloride (MsCl) in N-methyl morpholine (NMM) took place smoothly to give the corresponding mesylate 235 in 91% yield. Direct mesylate displacement with 3-aminopropanol and subsequent amine protection as the carbamate ((Boc)2O) in a one-pot fashion provided the corresponding Boc-amino propanol product 236 in 95% yield over 2 steps. With the acyclic diazepane precursor 236 in hand, employment of the intramolecular Fukuyama-Mitsunobu N-alkyl cyclization conditions (diisopropyl azodicarboxylate (DIAD)/PPh3) allowed generation of the diazepane in 75% yield. Nosyl group cleavage with thiophenol/K2CO3 provided the Boc-diazepane 237 in 65% overall yield and 98% purity following a pH-controlled aqueous workup. Finally, 4-fluoroisoquinoline- 5-sulfonyl chloride (238)?aprepared via subjection of 4- fluoroisoquinoline (239) to sulfur trioxide and sulfuric acid followed by treatment with thionyl chloride and finally 4 N HCl in ethyl acetate?awas involved in a 1-pot, two-step procedure in which this sulfonyl chloride was coupled with diazepane 237 (TEA/MeCN) to access the ripasudil framework in quantitative yield. Synthesis of the final drug target by deprotection with 4 M HCl in ethyl acetate followed by neutralization with aqueous sodium hydroxide provided the free base of ripasudil in 93% yield and 99.8% purity. Conversion to the more stable hydrochloride dihydrate form could be performed by treatment of the free base with 1 M HCl/EtOH and subsequent heating of the hydrochloride in H2O/acetone to provide ripasudil hydrochloride dihydrate XXIX in 83% yield.

in vivo

in optic nerve crush (nc) c57bl/6 mice model, oral administration of k-115 (1 mg/kg/d) increased 34 ± 3% survival of rgcs after nc [2].

IC 50

ROCK2: 19 nM (IC₅₀); ROCK1: 51 nM (IC₅₀); CaMKIIa: 370 nM (IC₅₀); PKACa: 2.1 μM (IC₅₀); PKC: 27 μM (IC₅₀)

References

shimokawa h, takeshita a. rho-kinase is an important therapeutic target in cardiovascular medicine[j]. arteriosclerosis, thrombosis, and vascular biology, 2005, 25(9): 1767-1775.yamamoto k, maruyama k, himori n, et al. the novel rho kinase (rock) inhibitor k-115: a new candidate drug for neuroprotective treatment in glaucomanovel rho kinase inhibitor[j]. investigative ophthalmology & visual science, 2014, 55(11): 7126-7136.tanihara h, inoue t, yamamoto t, et al. phase 1

Ripasudil hydrochloride dihydrate Preparation Products And Raw materials

Raw materials

Preparation Products

Less

Ripasudil hydrochloride dihydrate Suppliers

China 98 India 2 United Kingdom 2 United States 9 Global 111

Chemvon Biotechnology Co., Ltd

Tel: 021-50790412
Fax: +86-21-50790419
Email: info@chemvon.com
Country: China
ProdList: 371
Advantage: 57

Dalian Meilun Biotech Co., Ltd.

Tel: 0411-62910999 13889544652
Email: sales@meilune.com
Country: China
ProdList: 4747
Advantage: 58

Shanghai Topbiochem Technology Co., Ltd

Tel: 021-58170097
Email: info@topbiochem.com
Country: China
ProdList: 9510
Advantage: 58

Haoyuan Chemexpress Co., Ltd.

Tel: 021-58950125
Fax: (86) 21-58955996
Email: info@chemexpress.com
Country: China
ProdList: 7552
Advantage: 61

UHN Shanghai Research & Development Co., Ltd.

Tel: 021-58958002 18930822973
Fax: +86 (21) 5895-8628
Email: sales@uhnshanghai.com
Country: China
ProdList: 998
Advantage: 58

Hygeia (Chengdu) pharmaceutical technique Co., Ltd

Tel: 028-84502008 13568869383
Fax: 028-66476329
Email: sales@hygeiapharm.com
Country: China
ProdList: 296
Advantage: 55

Suzhou Haiheng Biological Pharmaceutical Co., Ltd.

Tel: 0512-65045967 15365387483
Fax: 15365387483
Email: sales@haihengpharm.com
Country: China
ProdList: 95
Advantage: 55

SPIRO PHARMA

Tel
Fax: -
Email: eric_feng1954@126.com
Country: China
ProdList: 9248
Advantage: 55

Pharmacodia (Beijing) Co.,Ltd

Tel: +86-400-851-9921
Fax: +86-10-82826195
Email: sales@pharmacodia.com
Country: China
ProdList: 2317
Advantage: 55

Shanghai EFE Biological Technology Co., Ltd.

Tel: 021-65675885 18964387627
Fax: 021-65675885
Email: info@efebio.com
Country: China
ProdList: 9803
Advantage: 58

Guangzhou QiYun Biotechnology Co., Ltd.

Tel: 020-61288194 61288195
Fax: 020-61288700
Email: 505721671@qq.com
Country: China
ProdList: 3866
Advantage: 58

Shanghai YuanYe Biotechnology Co., Ltd.

Tel: 021-61312847; 18021002903
Fax: QQ:3008007432
Email: 3008007409@qq.com
Country: China
ProdList: 71826
Advantage: 60

ShangHai Biochempartner Co.,Ltd

Tel: 177-54423994 17754423994
Fax: QQ:2853530913
Email: 2853530910@QQ.com
Country: China
ProdList: 8000
Advantage: 62

Beijing Solarbio Science & Tecnology Co., Ltd.

Tel: 010-50973130 18101056239
Email: 3193328036@qq.com
Country: China
ProdList: 29759
Advantage: 68

Amadis Chemical Company Limited

Tel: 571-89925085
Fax: 0086-571-89925065
Email: sales@amadischem.com
Country: China
ProdList: 131957
Advantage: 58

Medi-tech Bioscientific Co., Ltd.

Tel: 0519-83246372 13585352506
Fax: 0519-83246372
Country: China
ProdList: 1844
Advantage: 58

Lynnchem

Tel: 86-(0)29-85992781 17792393971
Email: info@lynnchem.com
Country: China
ProdList: 4587
Advantage: 58

Shanghai Jizhi Biochemical Technology Co. Ltd.

Tel: 4009004166/18616739031 18616739031
Email: 3007523370@qq.com
Country: China
ProdList: 52687
Advantage: 58

Fan De(Beijing) Biotechnology Co., Ltd.

Tel: 15911056312
Email: liming@bio-fount.com
Country: China
ProdList: 9729
Advantage: 58

Guangzhou Tomums Life Science Co., Ltd.

Tel: 020-31155029 18902330969
Fax: 020-31155029
Email: sales@tomums.cn
Country: China
ProdList: 4696
Advantage: 58

Dayang Chem (Hangzhou) Co.,Ltd.

Tel: +86-0571-88938639 +8617705817739
Fax: +86-571-88938652，+86-571- 88492614
Email: info@dycnchem.com
Country: China
ProdList: 52846
Advantage: 58

AFINE CHEMICALS LIMITED

Tel: +86-0571-85134551
Fax: 008657185134895
Email: sales@afinechem.com
Country: China
ProdList: 15107
Advantage: 58

Shanxi Xuanran Import and Export Trade Co., Ltd.

Tel: +8617735180244
Email: mike_yan@xuanranglobal.com
Country: CHINA
ProdList: 4017
Advantage: 58

Career Henan Chemica Co

Tel: +86-0371-86658258 +8613203830695
Fax: 0371-86658258
Email: laboratory@coreychem.com
Country: China
ProdList: 30229
Advantage: 58

Shanghai Jiegu Biotechnology Co., Ltd.

Tel: 021-51698675
Email: sales@jiejiegroup.com
Country: China
ProdList: 8020
Advantage: 58

Absin Bioscience Inc.

Tel: 021-38015121 18438616290
Email: lanwu@univ-bio.com
Country: China
ProdList: 24731
Advantage: 58

Shanghai hongqu biomedical technology co. LTD

Tel: 88888888888
Email: hongquchem@qq.com
Country: China
ProdList: 5132
Advantage: 58

Shanghai Luofa Biochemical Technology Co., Ltd.

Tel: 021-51111890 15317326293
Email: sales@molnova.com
Country: China
ProdList: 4195
Advantage: 58

Chunchuang (Wuhan) Technology Co., Ltd

Tel: 15727060112
Email: yutianchun2007@126.com
Country: China
ProdList: 9814
Advantage: 58

Wuhan Yanzhe Technology Co., Ltd

Tel: 15527250409
Fax: QQ：2692360204
Email: wenhaotian12@163.com
Country: China
ProdList: 4171
Advantage: 58

MedBioPharmaceutical Technology Inc

Tel: 021-69568360 18916172912
Email: order@med-bio.cn
Country: China
ProdList: 8140
Advantage: 58

Suzhou QIHANG Biotechnology Co., Ltd

Tel: 18662190603
Email: 437347250@qq.com
Country: China
ProdList: 4674
Advantage: 58

Wuhan Topule

Tel: +86-02787215551 +86-19945035818
Fax: 027-87215551
Email: 2936752263@qq.com
Country: China
ProdList: 7984
Advantage: 58

Shanghai Sunway Pharmaceutical Technology Co.,Ltd.

Tel: 021-51816796-820 13611835272
Fax: 021-5161 3951
Email: sales2@sunwaypharm.com
Country: China
ProdList: 44119
Advantage: 58

Abmole Bioscience Inc.

Tel: 021-50967598 02150967598
Email: sales@abmole.cn
Country: China
ProdList: 4494
Advantage: 58

Beijing Jin Ming Biotechnology Co., Ltd.

Tel: 010-60605840 15801484223;
Email: psaitong@jm-bio.com
Country: China
ProdList: 29757
Advantage: 58

Foshan Treasure Biotechnology Co., Ltd

Tel: 0757-85921206 18520245316
Email: 2329783215@qq.com
Country: China
ProdList: 12661
Advantage: 58

JinOu Biomedical (Nanjing) Co., Ltd.

Tel: 13000000000
Fax: jinoupharma@163
Email: jinoupharma@163.com
Country: China
ProdList: 11721
Advantage: 58

Nantong Feiyu Biological Technology CO.,LTD

Tel: 0513-68819626; 15152877458
Fax: 0513-68669626
Email: feiyubio@163.com
Country: China
ProdList: 4817
Advantage: 58

Hubei Kele Fine Chemical Co., Ltd

Tel: 027-59101668 19945030958
Fax: 027-59101668
Email: 2881924765@qq.com
Country: China
ProdList: 7936
Advantage: 58

ChemeGen

Tel: 18818260767
Fax: QQ 3610331285
Email: 2625930290@qq.com
Country: China
ProdList: 6973
Advantage: 58

Bide Pharmatech Ltd.

Tel: 400-1647117 13681763483
Email: product02@bidepharm.com
Country: China
ProdList: 59936
Advantage: 58

Wuhan Yingnuo Pharmaceutical Technology Co., Ltd.

Tel: 15387063101
Email: 2881924050@qq.com
Country: China
ProdList: 9957
Advantage: 58

Henan Alpha Chemical Co., Ltd.

Tel: 0371-55013243 15324716602
Email: 2853979810@qq.com
Country: China
ProdList: 9898
Advantage: 58

https://hanhongsci.com/

Tel: 021-54306202 18917919676
Email: info@hanhongsci.com
Country: China
ProdList: 29995
Advantage: 58

Wuhan Acumen Bio-Technology Co.,ltd

Tel: 027-027-16602739303 16602739303
Email: 673003916@qq.com
Country: China
ProdList: 2935
Advantage: 58

Hangzhou Bingochem Co., Ltd.

Tel: 0571-8512-5372
Email: sales@bingochem.com
Country: China
ProdList: 21669
Advantage: 58

Nanjing Shizhou Biology Technology Co.,Ltd

Tel: 025-85560043 15850508050
Fax: 025-85563444
Email: cindy.huang@synzest.com
Country: China
ProdList: 12000
Advantage: 58

Shanghai Aladdin Biochemical Technology Co.,Ltd.

Tel: 400-6206333 13167063860
Email: anhua.mao@aladdin-e.com
Country: China
ProdList: 48457
Advantage: 58

Shanghai jerryxing Biomedical Technology Co., Ltd

Tel: 17721492509; 17721492509
Email: 643638326@qq.com
Country: China
ProdList: 4970
Advantage: 58

887375-67-9, Ripasudil hydrochloride dihydrateRelated Search:

4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile Riociguat LEE011 Ripasudil Ripasudil Hydrochloride

K-115 HCL

Ripasudil free base

RipasudilHCl Hydrate

K115 HCl Dihydrate

RIPASUDIL HYDROCHLORIDE HYDRATE

(2S)-1-[(4-Fluoro-5-isoquinolinyl)sulfonyl]hexahydro-2-methyl-1H-1,4-diazepine monohydrochloride dihydrate

K-115 (HCl H2O)

Ripasudil HCl Dihydrate

K115 HCL 2H2O

Ripasudil Hydrochloride Dihydrate

Ripasudil (K-115)

K-115 Hydrochloride Dihydrate

Ripasudil (K-115), 98%, a highly selective and potent Rho-kinase inhibitor

Ripasudil(K-115)hydrochloridedihydrate

Ripasudil (K115) dihydrate

K 115; K115

Ripasudil dihydrate (K15)

Ripasudil Monohydrochloride Dihydrate

Ripasudil hydrochloride dihydrate（ K115 ）

4-Fluoro-5-[(2S)-2-methyl-1,4-diazepane-1-sulfonyl]isoquinoline dihydrate hydrochloride

Ripasudil (K-115) HCl dihydrate

K 155 HCl dihydrate

K-115|||Ripasudil hydrochloride dihydrate

Ripasudil, 10 mM in DMSO

887375-67-9

C15H23ClFN3O4S

C15H18FN3O2SHCl2H2O

C15H18FN3O2SClH2H2O