4-フルオロ-5-{[(2S)-2-メチル-1,4-ジアゼパン-1-イル]スルホニル}イソキノリン
Ripasudil
基本情報
- CAS
223645-67-8- 標準SMILES
C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12- InChIKey
QSKQVZWVLOIIEV-NSHDSACASA-N- 分子式
- C15H18FN3O2S
- 平均分子量
- 323.4 g/mol
- 単同位体質量
- 323.11037616
概要
Ripasudil is a member of isoquinolines.
名称と識別子
- 優先名称
- Ripasudil
- IUPAC
- 4-fluoro-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline
- 現地名
- 4-フルオロ-5-{[(2S)-2-メチル-1,4-ジアゼパン-1-イル]スルホニル}イソキノリン
- 英語名
- Ripasudil
- 分子式
- C15H18FN3O2S
- 分子量
- 323.39
名称と別名
Ripasudil223645-67-84-fluoro-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinolineK-321 anhydrous free base11978226XXDTXSID0010256091H-1,4-Diazepine, 1-((4-fluoro-5-isoquinolinyl)sulfonyl)hexahydro-2-methyl-, (2S)-Isoquinoline, 4-fluoro-5-(((2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl)sulfonyl)-ripasudilum4-fluoro-5-(((2S)-2-methyl-1,4-diazepan-1-yl)sulfonyl)isoquinoline1H-1,4-Diazepine, 1-[(4-fluoro-5-isoquinolinyl)sulfonyl]hexahydro-2-methyl-, (2S)-Isoquinoline, 4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]-
名称をさらに表示
4-フルオロ-5-[[(2S)-2β-メチルヘキサヒドロ-1H-1,4-ジアゼピン-1-イル]スルホニル]イソキノリン4-フルオロ-5-{[(2S)-2-メチル-1,4-ジアゼパン-1-イル]スルホニル}イソキノリン4-フルオロ-5-[[(2S)-2-メチルヘキサヒドロ-1H-1,4-ジアゼピン-1-イル]スルホニル]イソキノリンリパスジルCS-1564K-115, RipasudilRIPASUDIL HYDROCHLOIDEK 115 FREE BASE4-Fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline
RefChem:179484DTXCID001509873K-115 free baseRipasudil free basek115 Free baseRipasudil [INN](S)-4-Fluoro-5-((2-methyl-1,4-diazepan-1-yl)sulfonyl)isoquinolineCHEMBL3426621
データベース識別子
- CAS
223645-67-8- PubChem CID
- 9863672
- DTXSID
DTXSID001025609- ChEMBL
CHEMBL3426621- ChEBI
CHEBI:136046- UNII
- 11978226XX
- Nikkaji
- J3.122.028I
物性
構造計算による物性
- XLogP
- 1.5
- 極性表面積
- 70.7 Ų
- 水素結合供与体数
- 1
- 水素結合受容体数
- 6
- 回転可能結合数
- 2
- 重原子数
- 22
- 形式電荷
- 0
- 複雑度
- 482
実験および物理化学的性質
Drugs
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Sensory organs -> Ophthalmologicals
物理化学的性質
- 沸点
- 497.2 · 497.2±55.0 °C(Predicted)
- 比重(密度)
- 1.293 · 1.293±0.06 g/cm3(Predicted)
- 貯蔵温度
- 2 · under inert gas (nitrogen or Argon) at 2–8 °C
- 溶解性
- Soluble in DMSO
- 外見
- powder
- 酸解離定数(Pka)
- 9.7 · 9.70±0.40(Predicted)
- 色
- white to beige
- 水溶解度
- 2 O: · H2O: 2mg/mL, clear
- 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
- InChIKey
- QSKQVZWVLOIIEV-NSHDSACASA-N
- SMILES
- Fc1c2c(cnc1)cccc2[S](=O)(=O)N3[C@H](CNCCC3)C
安全と法規制
安全情報は参考情報です。供給元の安全データシート（SDS）、適用法令、専門家による評価に代わるものではありません。
安全データ
- wgk
- WGK 3
- ストレージクラス
- 11 - Combustible Solids
化学と産業
薬理情報
ATC Code
S - Sensory organs
QS - Sensory organs
Protein BindingThe plasma protein binding rate of Ripasudil is 55.4-59.8%
PharmacodynamicsRipasudil 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.
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 Schlemm’s 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 Schlemm’s 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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