(4,4-difluoro-2,7-diazaoct-2-yl)methanoate-2-methylpropan-2-yl ester | 122632-07-9

• 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: (4,4-difluoro-2,7-diazaoct-2-yl)methanoate-2-methylpropan-2-yl ester
• 英文别名: Methyl-(4-methylamino-butyl)-carbamic acid tert-butyl ester；tert-butyl N-methyl-N-[4-(methylamino)butyl]carbamate
• CAS: 122632-07-9
• 化学式: C₁₁H₂₄N₂O₂
• 分子量: 216.324
• InChiKey: FKJWKSFJVZBEEB-UHFFFAOYSA-N

物化性质

• 沸点：
  284.3±19.0 °C(Predicted)
• 密度：
  0.941±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P310,P332+P313,P362,P403+P233,P405,P501
• 危险品运输编号：
  1760
• 危险性描述：
  H315,H318,H335
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  (4,4-difluoro-2,7-diazaoct-2-yl)methanoate-2-methylpropan-2-yl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 N,N,N'-三甲基-1,4-丁二胺
  参考文献：
  名称：

  In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers

  摘要：

  The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.049
• 作为产物：
  描述：

  N,N'-二-BOC-1,4-丁二胺 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (4,4-difluoro-2,7-diazaoct-2-yl)methanoate-2-methylpropan-2-yl ester
  参考文献：
  名称：

  In vitro cytotoxicity on human ovarian cancer cells by T-type calcium channel blockers

  摘要：

  The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Ca(v)3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c-6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G(1) phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G(1) phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.049

文献信息

• New amino acid derivatives, processes for the preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0300189A2

  公开（公告）日：1989-01-25

  A compound of the formula : wherein R1 is lower alkyl optionally substituted with a substituent selected from the group consisting of acyl,hydroxy, lower alkoxy, aryl, lower alkylthio and a group of the formula : in which R5 is hydrogen or acyl and R6 is hydrogen or lower alkyl; aryl; or amino optionally substituted with substituent(s) selected from the group consisting of lower alkyl and acyl; and R2 is hydrogen or lower alkyl; or R1 and R2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with substituent(s) selected from the group consisting of lower alkyl, hydroxy(lower)alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl; R3 is hydrogen or lower alkyl; and R4 is lower alkyl; and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same.

  一种式如下的化合物 其中 R1 是低级烷基，可任选被选自以下组别的取代基取代：酰基、羟基、低级烷氧基、芳基、低级烷硫基和一个式......的基团： 其中 R5 为氢或酰基，且 R6 是氢或低级烷基；芳基；或被选自低级烷基和酰基的取代基任选取代的氨基；以及 R2 是氢或低级烷基；或 R1 和 R2 与所连接的氮原子一起形成杂环基团，该杂环基团可任选被选自由低级烷基、羟基（低级）烷基、低级烷氧基（低级）烷基、酰基（低级）烷基、氧代和酰基组成的取代基取代； R3 是氢或低级烷基；和 R4 是低级烷基； 及其药学上可接受的盐、制备工艺和包含这些成分的药物组合物。
• [EN] PYRIMIDINE HETEROCYCLIC COMPOUND, PREPARATION METHOD THEREFOR AND USE THEREOF IN MEDICINE<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE DE PYRIMIDINE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION EN MÉDECINE<br/>[ZH] 嘧啶杂环化合物，其制法与医药上的用途
  申请人：[en]INSILICO MEDICINE IP LIMITED;[zh]英矽智能科技知识产权有限公司

  公开号：WO2023116761A1

  公开（公告）日：2023-06-29

  一种嘧啶杂环化合物，其制法与医药上的用途。具体地，结构如式（A）所示的嘧啶杂环化合物或其药学上可接受的盐，各基团定义如说明书中所定义；包含所述化合物的药物组合物以及所述化合物在治疗细胞增殖性疾病（例如癌症）等中的用途。
• The total synthesis of argiotoxins 636, 659 and 673
  作者：V.John Jasys、Paul R. Kelbaugh、Deane M. Nason、Douglas Phillips、Nicholas A. Saccomano、Robert A. Volkmann

  DOI：10.1016/s0040-4039(00)82310-2

  日期：1988.1
• JASYS, V. JOHN;KELBAUGH, PAUL R.;NASON, DEANE M.;PHILLIPS, DOUGLAS;SACCOM+, TETRAHEDRON LETT., 29,(1988) N 48, C. 6223-6226
  作者：JASYS, V. JOHN、KELBAUGH, PAUL R.、NASON, DEANE M.、PHILLIPS, DOUGLAS、SACCOM+

  DOI：——

  日期：——
• SUBSTITUTED 4-PHENYL PYRIDINE COMPOUNDS AS NON-SYSTEMIC TGR5 AGONISTS
  申请人：Ardelyx, Inc.

  公开号：EP3390382B1

  公开（公告）日：2021-12-01