tert-butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[2-(3-chloroanilino)-2-oxoethyl]piperazine-1-carboxylate
• 化学式: C₁₇H₂₄ClN₃O₃
• 分子量: 353.849
• InChiKey: RZYUZEFSQJQMPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-(3-chlorophenyl)-2-(piperazin-1-yl)acetamide trifluoroacetate
  参考文献：
  名称：

  Enzyme Inhibitors

  摘要：

  式(I)的化合物是极光激酶抑制剂：其中X是—N—、—CH2—N—、—CH2—CH—或—CH—；R1是式(IA)的基团，其中Z是—CH2—、—NH—、-O-、—S(O)—、—S—、—S(O)2或具有3-7个环原子的二价单环碳环或杂环基团；Alk是任选取代的二价C1-C6亚烷基基团；A是氢或任选取代的具有5-7个环原子的单环碳环或杂环环；r、s和t独立地为0或1，前提是当A为氢时，至少一个r和s为1；R2是卤素、—CN、—CF3、—OCH3或环丙基；R3是式(IB)的基团，其中Q是氢或任选取代的苯基或具有5或6个环原子的单环杂环环；Z<1>是—S—、—S(O)—、—S(O)2—、—O—、—SO2NH—、—NHSO2—、NHC(═O)NH、—NH(C═S)NH—或—N(R4)—，其中R4是氢、C1-C3烷基、环烷基或苄基；Alk<1>和Alk<2>独立地是任选取代的二价C1-C3亚烷基基团；m、n和p独立地为0或1。数据来自esp@cenet数据库—Worldwide d77。

  公开号：

  US20090247507A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 TEA 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Lead discovery and optimization of T-type calcium channel blockers

  摘要：

  dA series of compounds were designed as T-type calcium channel blocker containing 6 or 5 pharmacophore features from structure-based virtual screening. To optimize the suggested structure, over 130 derivatives were synthesized and their inhibitory activities on T-type calcium channel were assayed using in vitro screening system with alpha 1(G) and alpha 1(H) clones. For the compounds with higher activities in FDSS assay system, the efficacy was measured by patch-clamp method. Among the library with 5 features, alkaneamide derivatives (7b, 9j, 11b, 11g, 11h) with 4-arylsubstituted piperazine showed better IC50 values than Mibefradil. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.004

文献信息

• Enzyme inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US08088761B2

  公开（公告）日：2012-01-03

  Compounds of formula (I), are aurora kinase inhibitors: wherein X is —N—, —CH2-N—, —CH2-CH—, or —CH—; R1 is a radical of formula (IA) wherein Z is —CH2-, —NH—, -0-, —S(O)— —S—, —S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, —CN, —CF3, —OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z&It;1> is —S—, —S(O)—, —S(O)2-, —O—, —SO2NH—, —NHSO2-, NHC(═O)NH, —NH(C═S)NH—, Or —N(R4)— wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk&It;1> and Alk&It;2> are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently 0 or 1.

  式（I）的化合物是极光激酶抑制剂：其中X是- N-，- CH2-N-，- -CH-或- CH-；R1是式（IA）的基团，其中Z是- -，- NH-，- 0-，- S（O）-，- S-，- S（O）2或具有3-7个环原子的二价单环芳环或杂环基团；Alk是可选取代的二价C1-C6烷基链基团；A是氢或具有5-7个环原子的可选取代的单环芳环或杂环；r，s和t独立地为0或1，前提是当A为氢时，至少有一个r和s为1；R2是卤素，- CN，- CF3，- OCH3或环丙基；R3是式（IB）的基团，其中Q是氢或可选取代的具有5或6个环原子的苯基或单环杂环；Z1是- S-，- S（O）-，- S（O）2-，- O-，- SO2NH-，- NHSO2-，NHC（=O）NH，- NH（C= S）NH-或- N（R4）-，其中R4是氢，C1-C3烷基，环烷基或苯甲基；Alk1和Alk2是独立的可选取代的二价C1-C3烷基链基团；m，n和p独立地为0或1。
• Imidazo[4,5-<i>b</i>]pyridine Derivatives As Inhibitors of Aurora Kinases: Lead Optimization Studies toward the Identification of an Orally Bioavailable Preclinical Development Candidate
  作者：Vassilios Bavetsias、Jonathan M. Large、Chongbo Sun、Nathalie Bouloc、Magda Kosmopoulou、Mizio Matteucci、Nicola E. Wilsher、Vanessa Martins、Jóhannes Reynisson、Butrus Atrash、Amir Faisal、Frederique Urban、Melanie Valenti、Alexis de Haven Brandon、Gary Box、Florence I. Raynaud、Paul Workman、Suzanne A. Eccles、Richard Bayliss、Julian Blagg、Spiros Linardopoulos、Edward McDonald

  DOI：10.1021/jm100262j

  日期：2010.7.22

  Lead optimization studies using 7 as the starting point led to a new class of imidazo[4,5-b]pyridine-based inhibitors of Aurora kinases that possessed the 1-benzylpiperazinyl motif at the 7-position, and displayed favorable in vitro properties. Cocrystallization of Aurora-A with 40c (CCT137444) provided a clear understanding into the interactions of this novel class of inhibitors with the Aurora kinases. Subsequent physicochemical property refinement by the incorporation of solubilizing groups led to the identification of 3-((4-(6-bromo-2-(4-(4-methylpiperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)methyl)-5-methylisoxazole (51, CCT137690) which is a potent inhibitor of Aurora kinases (Aurora-A IC(50) = 0.015 +/- 0.003 muM, Aurora-B IC(50) = 0.025 muM, Aurora-C IC(50) = 0.019 muM). Compound 51 is highly orally bioavailable, and in in vivo efficacy studies it inhibited the growth of SW620 colon carcinoma xenografts following oral administration with no observed toxicities as defined by body weight loss.
• ENZYME INHIBITORS
  申请人：Cancer Research Technology Limited

  公开号：EP1963315B1

  公开（公告）日：2014-10-08
• US8088761B2
  申请人：——

  公开号：US8088761B2

  公开（公告）日：2012-01-03
• [EN] ENZYME INHIBITORS<br/>[FR] INHIBITEURS D'ENZYMES
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2007072017A2

  公开（公告）日：2007-06-28

  [EN] Compounds of of formula (I), are aurora kinase inhibitors:wherein X is -N-, -CH₂-N-, -CH₂-CH-, or -CH-; R₁ is a radical of formula (IA) wherein Z is -CH₂-, -NH-, -0-, -S(O)- -S-, -S(O)₂ or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C₁-C₆ alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1 , provided that when A is hydrogen then at least one of r and s is 1 ; R₂ is halogen, -CN, -CF₃, -OCH₃, or cyclopropyl; and R₃ is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z¹ is -S-, -S(O)-, -S(O)₂-, -O-, -SO₂NH-, -NHSO₂-, NHC(=O)NH, -NH(C=S)NH-, Or -N(R₄)- wherein R₄ is hydrogen, C₁-C₃ alkyl, cycloalkyl, or benzyl; and Alk¹ and Alk² are, independently, optionally substituted divalent C1-C₃ alkylene radicals; and m, n and p are independently 0 or 1.
  [FR] L'invention concerne des composés représentés par la formule générale (I). Ces composés sont des inhibiteurs d'Aurora kinases. Dans ladite formule, X désigne un groupe -N-, -CH₂-N-, -CH₂-CH-, ou -CH-°; R₁ désigne un radical représenté par la formule générale (IA), dans laquelle Z désigne un groupe -CH₂-, -NH-, -O-, -S(O)- -S-, -S(O)₂ ou un radical hétérocyclique ou carbocyclique monocyclique divalent comportant 3-7 atomes par cycle°; Alk désigne un radical alkylène C₁-C₆ divalent éventuellement substitué ; A désigne un atome d'hydrogène ou un noyau hétérocyclique ou carbocyclique monocyclique éventuellement substitué comportant 5-7 atomes par cycle°; r, s et t valent chacun 0 ou 1, à condition que lorsque A désigne un atome d'hydrogène, alors r et/ou s vaut 1 ; R₂ désigne un groupe halogène, -CN, -CF₃, -OCH₃, ou cyclopropyle°; et R₃ désigne un radical représenté par la formule générale (IB), dans laquelle Q désigne un atome d'hydrogène ou un noyau hétérocyclique monocyclique ou phényle éventuellement substitué comportant 5-6 atomes par cycle ; Z¹ désigne un groupe -S-, -S(O)-, -S(O)₂-, -O-, -SO₂NH-, -NHSO₂-, NHC(=O)NH, -NH(C=S)NH-, ou -N(R₄)-, R₄ désignant un atome d'hydrogène, un groupe alkyle C₁-C₃, cycloalkyle, ou benzyle°; et Alk¹ et Alk² désignent, chacun des radicaux alkylène C₁-C₃ divalents éventuellement substitués ; et m, n et p valent chacun 0 ou 1.