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クリゾチニブ

クリゾチニブ  化学構造式
877399-52-5
CAS番号.
877399-52-5
化学名:
クリゾチニブ
别名:
クリゾチニブ;3-[(1R)-1-(2,6-ジクロロ-3-フルオロフェニル)エトキシ]-5-[1-(4-ピペリジニル)-1H-ピラゾール-4-イル]-2-ピリジンアミン;クリゾチニブ (JAN)
英語化学名:
Crizotinib
英語别名:
CS-164;Xalkori;Crizotini;Crozotinib;Crizotinib;PF 2341066;PF-02341066;(R)-Crizotinib;Crizotinib, >=98%;Crizotinib fandachem
CBNumber:
CB12473904
化学式:
C21H22Cl2FN5O
分子量:
450.34
MOL File:
877399-52-5.mol

クリゾチニブ 物理性質

融点 :
192 °C
沸点 :
599.2±50.0 °C(Predicted)
比重(密度) :
1.47±0.1 g/cm3(Predicted)
貯蔵温度 :
room temp
外見 :
powder
酸解離定数(Pka):
9.81±0.10(Predicted)
色:
white to tan
CAS データベース:
877399-52-5
安全性情報
  • リスクと安全性に関する声明
  • 危険有害性情報のコード(GHS)
Sフレーズ  24/25
RIDADR  UN 3077 9 / PGIII
WGK Germany  3
国連危険物分類  IRRITANT
HSコード  29333990
絵表示(GHS)
注意喚起語 Warning
危険有害性情報
コード 危険有害性情報 危険有害性クラス 区分 注意喚起語 シンボル P コード
H317 アレルギー性皮膚反応を起こすおそれ 感作性、皮膚 1 警告 P261, P272, P280, P302+P352,P333+P313, P321, P363, P501
H319 強い眼刺激 眼に対する重篤な損傷性/眼刺激 性 2A 警告 P264, P280, P305+P351+P338,P337+P313P
H341 遺伝性疾患のおそれの疑い 生殖細胞変異原性 2 警告 P201,P202, P281, P308+P313, P405,P501
H400 水生生物に強い毒性 水生環境有害性、急性毒性 1 警告 P273, P391, P501
注意書き
P273 環境への放出を避けること。
P280 保護手袋/保護衣/保護眼鏡/保護面を着用するこ と。
P305+P351+P338 眼に入った場合:水で数分間注意深く洗うこと。次にコ ンタクトレンズを着用していて容易に外せる場合は外す こと。その後も洗浄を続けること。

クリゾチニブ 価格 もっと(15)

メーカー 製品番号 製品説明 CAS番号 包装 価格 更新時間 購入
富士フイルム和光純薬株式会社(wako) W01COBQE-4059 クリゾチニブ
Crizotinib
877399-52-5 1g ¥57600 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01COBQE-4059 クリゾチニブ
Crizotinib
877399-52-5 5g ¥180000 2018-12-26 購入
Sigma-Aldrich Japan PZ0191 ≥98% (HPLC)
Crizotinib ≥98% (HPLC)
877399-52-5 5mg ¥18160 2021-03-23 購入
富士フイルム和光純薬株式会社(wako) W01TRCC785000 クリゾチニブ
Crizotinib
877399-52-5 10mg ¥18800 2018-12-26 購入
富士フイルム和光純薬株式会社(wako) W01TRCC785000 クリゾチニブ
Crizotinib
877399-52-5 25mg ¥23800 2018-12-26 購入

クリゾチニブ 化学特性,用途語,生産方法

用途

c-MET 及び ALK の強力な阻害剤です。さまざまながんモデルで抗がん作用を示します。 

用途

c-MET 及び ALK の強力な阻害剤です。様々ながんモデルで抗がん作用を示します。 ヒトがん細胞において、c-MET 依存性の細胞増殖、遊走、浸潤を阻害します(in vitro)。 経口活性があります。

効能

抗悪性腫瘍薬, 融合型チロシンキナーゼ阻害薬

商品名

ザーコリ (ファイザー)

説明

In August 2011, the United States FDA approved crizotinib (PF- 02341066) for the treatment of anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). Crizotinib is a dual ATP competitive inhibitor of tyrosine kinases c-MET (Mesenchymal-Epithelial Transition Factor) kinase (cellular IC50=8 nM) and ALK (cellular IC50=20 nM), both of which are important targets for cancer chemotherapy. When crizotinib was tested for selectivity versus other kinases it was found to have enzyme IC50's within 100-fold multiples of c-MET for 13 of the 120 kinases tested. In cellular assays, crizotinib was found to inhibit RON (recepteur d’origine nantais) kinase with a 10-fold selectivity window over c-MET.

化学的特性

White Solid

Originator

Pfizer (United States)

使用

A potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). A potential antitumor agent.

使用

Crizotinib is a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). Crizotinib is a potential antitumor agent.

使用

PF-2341066 (Crizotinib) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM, respectivley

定義

ChEBI: A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients wi h locally advanced or metastatic non-small cell lung cancer (NSCLC)

適応症

Crizotinib (Xalkori(R), Pfizer), approved in 2011, was the first approved inhibitor targeting anaplastic lymphoma kinase (ALK). ROS protooncogene 1-encoded kinase (ROS1) of the tyrosine kinase insulin receptor class and MET proto-oncogene-encoded kinase of the hepatocyte growth factor receptor (HGFR) class are other kinases targeted by crizotinib.When approved in 2011, crizotinib was the first drug specifically targeting NSCLC patients. However, resistance to crizotinib was usually observed in approximately 8 months after initial application and more than half of crizotinib-treated patients experienced gastrointestinal side effects. In 2016,crizotinib was additionally approved for ROS1-positive NSCLC by FDA.

brand name

Xalkori

臨床応用

More recent studies have shown that patients with MET amplification and no ALK rearrangement treated with crizotinib have responded well in NSCLC and squamous cell lung carcinoma.
Crizotinib is a potent and selective mesenchymal epithelial transition factor/anaplastic lymphoma kinase (cMET/ALK) inhibitor. Marketed under the brand name Xalkori, crizotinib was discovered and developed by Pfizer and is approved for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) that is caused by the echinoderm microtubule associated proteinlike 4 (EML4) mutation of ALK. Crizotinib is also undergoing clinical evaluation against additional cancers which express the ALK mutation, such as advanced disseminated anaplastic large-cell lymphoma and neuroblastoma.

Chemical Synthesis

Several synthetic routes for the preparation of crizotinib have been reported, each employing a very similar convergent strategy. The synthesis utilized to prepare over 100 kg is described in the scheme.


Mesylation of tert-butyl-4-hydroxypiperidine-1-carboxylate (116) followed by displacement with 4-iodopyarazole (117) provided iodopyrazine 118 in 50–60% overall yield for the two steps. Reaction of iodide 118 with i-PrMgCl furnished the corresponding Grignard reagent, which was quenched with borolane 119 to give the arylboronate 120 in 70–80% yield after crystallization from ethanol/water. The Suzuki coupling partner of 120 (bromide 126) was prepared in several steps starting with enzymatic reduction of 2,6-dichloro-3-fluoroacetophenone (121) using an engineered ketoreductase process, providing alcohol 122 in 94% yield and in >99% ee. Mitsunobu reaction with 3-hydroxy-2-nitropyridine (123) provided nitropyridine 124 in 80–85% yield after crystallization from ethanol and with no loss in enantiopurity. Chemoselective reduction of the nitro group was accomplished through hydrogenation using 10% sponge-nickel catalyst to give amine 125 in 95% yield after crystallization from methanol. Regioselective bromination of 125 using NBS in CH3CN/CH2Cl2, followed by a bisulfate quench and Et3N wash (to purge residual succinimide) and subsequent crystallization from methanol provided Suzuki- Miyaura coupling partner 126 in 80–85% yield. Coupling of arylbromide 126 with arylboronate 120 was accomplished using 0.8 mol % PdCl2(dppf)CH2Cl2 as the catalyst, followed by treatment with cysteine on silica-alumina to purge residual palladium. Crystallization of the resulting mixture from heptanes provided the coupled product in 76–80% yield, which upon acid-promoted removal of the Boc protecting group and crystallization from CH3CN/H2O produced crizotinib (X) in 75–80% yield.

クリゾチニブ 上流と下流の製品情報

原材料

準備製品


クリゾチニブ 生産企業

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877399-52-5(クリゾチニブ )キーワード:


  • 877399-52-5
  • 3-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]-2-aMinopyridine
  • (R)-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H- pyrazol-4-yl)pyridin-2-ylaMine
  • [3-[[(R)-1-(2,6-Dichloro-3- fluorophenyl)ethyl]oxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-yl]aMine
  • 2-PyridinaMine, 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-
  • Crozotinib
  • Crizotinib,PF-02341066
  • Xalkori
  • Crizotinib Xalkori
  • 3-[(1R)-1-(2,6-DICHLORO-3-FLUOROPHENYL)ETHOXY]-5-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]PYRIDIN-2-AMINE
  • 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
  • (R)-Crizotinib
  • PF 2341066; PF2341066
  • CS-164
  • PF 02341066 - Crizotinib | PF 2341066
  • Crizotinib ? ?3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
  • Crizotinib (PF2341066)
  • PF-02341066 Crizotinib
  • 3-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine
  • k-ras(g12c) inhibitor 6 NA Crizotinib
  • Crizotinib, >=98%
  • 3-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridin
  • 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-Pyridinamine
  • (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine
  • 3-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]pyridin-2-amine
  • Crizotinib
  • PF 2341066
  • PF-02341066
  • PF-2341066/Crizotinib
  • 3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine
  • Crizotinib fandachem
  • クリゾチニブ
  • 3-[(1R)-1-(2,6-ジクロロ-3-フルオロフェニル)エトキシ]-5-[1-(4-ピペリジニル)-1H-ピラゾール-4-イル]-2-ピリジンアミン
  • クリゾチニブ (JAN)
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