CN106132922A - 一类水溶性丙泊酚衍生物及其用途 - Google Patents

一类水溶性丙泊酚衍生物及其用途 Download PDF

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CN106132922A
CN106132922A CN201580008926.8A CN201580008926A CN106132922A CN 106132922 A CN106132922 A CN 106132922A CN 201580008926 A CN201580008926 A CN 201580008926A CN 106132922 A CN106132922 A CN 106132922A
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propofol
acid
fluoro
derivative
water
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CN106132922B (zh
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李勤耕
王涛
吴酮
曾令国
王元忠
毛伟
陈刚
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Jiangsu Nhwaluokang Pharmceutical Research And Development Co ltd
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    • C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
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    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
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Abstract

本发明公开了一类水溶性丙泊酚衍生物、其制备方法、使用其的麻醉方法、其作为前药的用途以及其在制备静脉麻醉药物中的用途。所述水溶性丙泊酚衍生物具有通式(I)：其中，X为H或F；Y为F或者被一个或多个F取代的烷基；n为1、2、3、4、5或6；W为W1或W2；W1为NR1R2·A或R1、R2各自独立地为H、任选地被苯基取代的烷基、或环烷基；m为0、1、2或3；A为药学可接受的酸；W2为COOM1/t或OPO3(M)2/t或PO3(M)2/t；M为可与酸根成盐的金属离子、铵离子或碱性氨基酸阳离子；t为M所带的电荷数。

Description

PCT国内申请，说明书已公开。

Claims (30)

  1. PCT国内申请，权利要求书已公开。
CN201580008926.8A 2014-02-17 2015-02-16 一类水溶性丙泊酚衍生物及其用途 Active CN106132922B (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
CN2014100538777 2014-02-17
CN201410053877 2014-02-17
CN2014100531299 2014-02-17
CN201410053129 2014-02-17
CN201410154994 2014-04-17
CN201410154956 2014-04-17
CN2014101549942 2014-04-17
CN2014101549567 2014-04-17
PCT/CN2015/073171 WO2015120821A1 (zh) 2014-02-17 2015-02-16 一类水溶性丙泊酚衍生物及其用途

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CN106132922B CN106132922B (zh) 2018-12-04

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116023284A (zh) * 2021-10-26 2023-04-28 中山万汉制药有限公司 丙泊酚衍生物与药学上可接受的酸的加成盐及其组合物与用途

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10239851B2 (en) 2014-02-17 2019-03-26 Qingeng Li Carboxylic acid derivatives and use thereof in the preparation of prodrugs
US11439653B1 (en) 2021-03-30 2022-09-13 Epalex Corporation Fospropofol formulations
US11547714B2 (en) 2020-02-05 2023-01-10 Epalex Corporation Fospropofol salts, methods and compositions
US11628178B2 (en) 2019-03-26 2023-04-18 Epalex Corporation Fospropofol methods and compositions
US11478490B1 (en) 2021-03-30 2022-10-25 Epalex Corporation Fospropofol formulations
WO2022133687A1 (zh) * 2020-12-21 2022-06-30 加拿大力邦制药有限公司 一种药物偶联物、及其制备方法和用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1907954A (zh) * 2006-08-16 2007-02-07 重庆医科大学医药研究所 麻醉药2,6－二异丙基苯酚的水溶性衍生物及其制备方法
CN101094840A (zh) * 2004-12-29 2007-12-26 韩美药品株式会社 抑制癌细胞生长的喹唑啉衍生物和制备其的方法
CN101361730A (zh) * 2008-09-19 2009-02-11 重庆医科大学医药研究所 异丙酚琥珀酸单酯钠盐在制备抗肿瘤药物中的用途
CN102020574A (zh) * 2009-09-14 2011-04-20 李勤耕 丙泊酚γ-氨基丁酸酯的衍生物及其制备方法

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6254853B1 (en) 1998-05-08 2001-07-03 Vyrex Corporation Water soluble pro-drugs of propofol
ZA200504940B (en) * 2003-01-28 2006-09-27 Xenoport Inc Amino acid derived prodrugs of propofol, compositions and uses thereof
US8173840B2 (en) * 2003-07-29 2012-05-08 Signature R&D Holdings, Llc Compounds with high therapeutic index
US7230003B2 (en) * 2003-09-09 2007-06-12 Xenoport, Inc. Aromatic prodrugs of propofol, compositions and uses thereof
WO2006017351A1 (en) * 2004-07-12 2006-02-16 Xenoport, Inc. Prodrugs of propofol, compositions and uses thereof
CN101313890A (zh) * 2007-05-28 2008-12-03 重庆医科大学医药研究所 2,6-二异丙基苯酚的n,n-二烷基氨基酸酯盐注射剂
CN101633671B (zh) * 2009-07-13 2011-10-05 杭州奥默医药技术有限公司 一种磷酰基羧酸丙泊酚酯衍生物及制备方法
CN101885735B (zh) * 2010-06-23 2012-09-12 四川大学华西医院 取代苯酚羟基酸酯的磷酸酯化合物、制备方法及在药物中的应用
CN102391137A (zh) * 2011-09-26 2012-03-28 成都一平医药科技发展有限公司 丙泊酚的氨基酸酯水溶性衍生物及其用途
US10239851B2 (en) * 2014-02-17 2019-03-26 Qingeng Li Carboxylic acid derivatives and use thereof in the preparation of prodrugs

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101094840A (zh) * 2004-12-29 2007-12-26 韩美药品株式会社 抑制癌细胞生长的喹唑啉衍生物和制备其的方法
CN1907954A (zh) * 2006-08-16 2007-02-07 重庆医科大学医药研究所 麻醉药2,6－二异丙基苯酚的水溶性衍生物及其制备方法
CN101361730A (zh) * 2008-09-19 2009-02-11 重庆医科大学医药研究所 异丙酚琥珀酸单酯钠盐在制备抗肿瘤药物中的用途
CN102020574A (zh) * 2009-09-14 2011-04-20 李勤耕 丙泊酚γ-氨基丁酸酯的衍生物及其制备方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116023284A (zh) * 2021-10-26 2023-04-28 中山万汉制药有限公司 丙泊酚衍生物与药学上可接受的酸的加成盐及其组合物与用途
CN116023284B (zh) * 2021-10-26 2023-09-22 中山万汉制药有限公司 丙泊酚衍生物与药学上可接受的酸的加成盐及其组合物与用途

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US20170050920A1 (en) 2017-02-23
EP3109229B1 (en) 2019-06-05
WO2015120821A1 (zh) 2015-08-20
CN106132922B (zh) 2018-12-04
EP3109229A1 (en) 2016-12-28
US9643917B2 (en) 2017-05-09
EP3109229A4 (en) 2017-07-12

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