5-(4-((5-amino-1,3,4-thiadiazol-2-yl)oxy)piperidin-1-yl)-1,3,4-thiadiazol-2-amine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-(4-((5-amino-1,3,4-thiadiazol-2-yl)oxy)piperidin-1-yl)-1,3,4-thiadiazol-2-amine
• 英文别名: 5-{4-[(5-Amino-1,3,4-thiadiazol-2-yl)oxy]piperidin-1-yl}-1,3,4-thiadiazol-2-amine；5-[4-[(5-amino-1,3,4-thiadiazol-2-yl)oxy]piperidin-1-yl]-1,3,4-thiadiazol-2-amine
• 化学式: C₉H₁₃N₇OS₂
• 分子量: 299.381
• InChiKey: RUDRLRZJXZZCQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  环丙乙酸 、 5-(4-((5-amino-1,3,4-thiadiazol-2-yl)oxy)piperidin-1-yl)-1,3,4-thiadiazol-2-amine 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以51%的产率得到2-cyclopropyl-N-(5-(4-((5-(2-cyclopropylacetamido)-1,3,4-thiadiazol-2-yl)oxy)piperidin-1-yl)-1,3,4-thiadiazol-2-yl)acetamide
  参考文献：
  名称：

  [EN] GLUTAMINASE INHIBITORS
  [FR] INHIBITEURS DE GLUTAMINASE

  摘要：

  一种化合物，或其药学上可接受的盐，其结构如下：公式A，其中A是一个环；Y1和Y2分别独立地是N或C，具有适当的价；X1和X2分别独立地是-NH-、-O-、-CH2-O-、-NH-CH2-或-N(CH3)-CH2-，但是当X1和X2中至少有一个是-CH2-O-、-NH-CH2-或-N(CH3)-CH2-时，那么-CH2-直接连接到A；a和b分别独立地是0或1；c和d分别独立地是0或1；Z1和Z2分别独立地是一个杂环；R1和R2分别独立地是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、氨基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；但是如果Y1和Y2分别是C，则a为1且b为1；如果Y1和Y2分别是N，则a为0且b为0；如果Y1是N且Y2是C，则a=0且b=1；如果Y1是C且Y2是N，则a=1且b=0；如果c=0且d=0，则R1和R2都是氨基；如果c为1且d为1，则R1和R2都不是氨基；如果c为0且d为1，则R1是氨基且R2是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；如果c为1且d为0，则R2是氨基且R1是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基。

  公开号：

  WO2016054388A1
• 作为产物：
  描述：

  tert-butyl 4-(((methylthio)carbonothioyl)oxy)piperidine-1-carboxylate 在 盐酸 、 三乙胺 、 肼 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 反应 5.0h， 生成 5-(4-((5-amino-1,3,4-thiadiazol-2-yl)oxy)piperidin-1-yl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  [EN] GLUTAMINASE INHIBITORS
  [FR] INHIBITEURS DE GLUTAMINASE

  摘要：

  一种化合物，或其药学上可接受的盐，其结构如下：公式A，其中A是一个环；Y1和Y2分别独立地是N或C，具有适当的价；X1和X2分别独立地是-NH-、-O-、-CH2-O-、-NH-CH2-或-N(CH3)-CH2-，但是当X1和X2中至少有一个是-CH2-O-、-NH-CH2-或-N(CH3)-CH2-时，那么-CH2-直接连接到A；a和b分别独立地是0或1；c和d分别独立地是0或1；Z1和Z2分别独立地是一个杂环；R1和R2分别独立地是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、氨基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；但是如果Y1和Y2分别是C，则a为1且b为1；如果Y1和Y2分别是N，则a为0且b为0；如果Y1是N且Y2是C，则a=0且b=1；如果Y1是C且Y2是N，则a=1且b=0；如果c=0且d=0，则R1和R2都是氨基；如果c为1且d为1，则R1和R2都不是氨基；如果c为0且d为1，则R1是氨基且R2是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；如果c为1且d为0，则R2是氨基且R1是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基。

  公开号：

  WO2016054388A1

文献信息

• [EN] GLUTAMINASE INHIBITORS<br/>[FR] INHIBITEURS DE GLUTAMINASE
  申请人：UNIV PITTSBURGH

  公开号：WO2016054388A1

  公开（公告）日：2016-04-07

  A compound, or a pharmaceutically acceptable salt thereof, having a structure of: Formula A wherein A is a ring; Y1 and Y2 are each independently N or C with the proper valency; X1 and X2 are each independently -NH-, -0-, -CH2-0-, -NH-CH2-, or -N(CH3)-CH2-, provided that when at least one of X1 and X2 is -CH2-0-, -NH-CH2-, or -N(CH3)-CH2- then the - CH2- is directly connected to A; a and b are each independently 0 or 1; c and d are each independently 0 or 1; Z1 and Z2 are each independently a heterocyclic; and R1 and R2 are each independently optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, amino, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; provided that if Y1 and Y2 are each C, then a is 1 and b is 1; provided that if Y1 and Y2 are each N, then a is 0 and b is 0; provided that if Y1 is N and Y2 is C, then a=0 and b=l; provided that if Y1 is C and Y2 is N, then a=l and b=0; provided that if c=0 and d=0, then R1 and R2 are both amino; provided that if c is 1 and d is 1, then both R1 and R2 are not amino; provided that if c is 0 and d is 1, then R1 is amino and R2 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; and provided that if c is 1 and d is 0, then R2 is amino and R1 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl.

  一种化合物，或其药学上可接受的盐，其结构如下：公式A，其中A是一个环；Y1和Y2分别独立地是N或C，具有适当的价；X1和X2分别独立地是-NH-、-O-、-CH2-O-、-NH-CH2-或-N(CH3)-CH2-，但是当X1和X2中至少有一个是-CH2-O-、-NH-CH2-或-N(CH3)-CH2-时，那么-CH2-直接连接到A；a和b分别独立地是0或1；c和d分别独立地是0或1；Z1和Z2分别独立地是一个杂环；R1和R2分别独立地是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、氨基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；但是如果Y1和Y2分别是C，则a为1且b为1；如果Y1和Y2分别是N，则a为0且b为0；如果Y1是N且Y2是C，则a=0且b=1；如果Y1是C且Y2是N，则a=1且b=0；如果c=0且d=0，则R1和R2都是氨基；如果c为1且d为1，则R1和R2都不是氨基；如果c为0且d为1，则R1是氨基且R2是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基；如果c为1且d为0，则R2是氨基且R1是可选择地取代的烷基、可选择地取代的芳基烷基、可选择地取代的环烷基、可选择地取代的杂芳基烷基、可选择地取代的烷基氧基、可选择地取代的烷基芳基氧基、可选择地取代的芳基、可选择地取代的杂芳基、或可选择地取代的杂环烷基。
• Glutaminase inhibitors
  申请人：University of Pittsburgh—Of the Commonwealth System of Higher Education

  公开号：US10245254B2

  公开（公告）日：2019-04-02

  A compound, or a pharmaceutically acceptable salt thereof, having a structure of: wherein A is a ring; Y1 and Y2 are each independently N or C with the proper valency; X1 and X2 are each independently —NH—, —O—, —CH2—O—, —NH—CH2—, or —N(CH3)—CH2—, provided that when at least one of X1 and X2 is —CH2—O—, —NH—CH2—, or —N(CH3)—CH2— then the —CH2— is directly connected to A; a and b are each independently 0 or 1; c and d are each independently 0 or 1; Z1 and Z2 are each independently a heterocyclic; and R1 and R2 are each independently optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, amino, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; provided that if Y1 and Y2 are each C, then a is 1 and b is 1; provided that if Y1 and Y2 are each N, then a is 0 and b is 0; provided that if Y1 is N and Y2 is C, then a=0 and b=1; provided that if Y1 is C and Y2 is N, then a=1 and b=0; provided that if c=0 and d=0, then R1 and R2 are both amino; provided that if c is 1 and d is 1, then both R1 and R2 are not amino; provided that if c is 0 and d is 1, then R1 is amino and R2 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; and provided that if c is 1 and d is 0, then R2 is amino and R1 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl.

  一种化合物或其药学上可接受的盐，具有以下结构： 其中 A 是一个环； Y1 和 Y2 各自独立地为具有适当价态的 N 或 C； X1和X2各自独立地为-NH-、-O-、-CH2-O-、-NH-CH2-或-N(CH3)-CH2-，条件是当X1和X2中至少有一个为-CH2-O-、-NH-CH2-或-N(CH3)-CH2-时，该-CH2-与A直接相连； a 和 b 各自独立地为 0 或 1； c 和 d 各自独立地为 0 或 1； Z1 和 Z2 各自独立地为杂环；以及 R1和R2各自独立地为任选取代的烷基、任选取代的芳基、任选取代的环烷基、氨基、任选取代的杂芳基、任选取代的烷氧基、任选取代的烷芳基氧基、任选取代的芳基、任选取代的杂芳基或任选取代的杂环烷基； 如果 Y1 和 Y2 均为 C，则 a 为 1，b 为 1； 如果 Y1 和 Y2 均为 N，则 a 为 0，b 为 0； 如果 Y1 是 N，Y2 是 C，则 a=0 和 b=1； 如果 Y1 是 C，Y2 是 N，则 a=1 和 b=0； 如果 c=0 和 d=0，则 R1 和 R2 都是氨基； 如果 c 为 1，d 为 1，则 R1 和 R2 都不是氨基； 如果 c 为 0，d 为 1，则 R1 为氨基，R2 为任选取代的烷基、任选取代的芳基、任选取代的环烷基、任选取代的杂烷基、任选取代的烷基烷氧基、任选取代的烷芳基氧基、任选取代的芳基、任选取代的杂芳基或任选取代的杂环烷基；和 条件是，如果 c 是 1，d 是 0，则 R2 是氨基，R1 是任选取代的烷基、任选取代的芳基、任选取代的环烷基、任选取代的杂烷基、任选取代的烷基烷氧基、任选取代的烷芳基氧基、任选取代的芳基、任选取代的杂芳基或任选取代的杂环烷基。
• GLUTAMINASE INHIBITORS
  申请人：University of Pittsburgh - Of the Commonwealth System of Higher Education

  公开号：US20170290815A1

  公开（公告）日：2017-10-12

  A compound, or a pharmaceutically acceptable salt thereof, having a structure of: wherein A is a ring; Y 1 and Y 2 are each independently N or C with the proper valency; X 1 and X 2 are each independently —NH—, —O—, —CH 2 —O—, —NH—CH 2 —, or —N(CH 3 )—CH 2 —, provided that when at least one of X 1 and X 2 is —CH 2 —O—, —NH—CH 2 —, or —N(CH 3 )—CH 2 — then the —CH 2 — is directly connected to A; a and b are each independently 0 or 1; c and d are each independently 0 or 1; Z 1 and Z 2 are each independently a heterocyclic; and R 1 and R 2 are each independently optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, amino, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; provided that if Y 1 and Y 2 are each C, then a is 1 and b is 1; provided that if Y 1 and Y 2 are each N, then a is 0 and b is 0; provided that if Y 1 is N and Y 2 is C, then a=0 and b=1; provided that if Y 1 is C and Y 2 is N, then a=1 and b=0; provided that if c=0 and d=0, then R 1 and R 2 are both amino; provided that if c is 1 and d is 1, then both R 1 and R 2 are not amino; provided that if c is 0 and d is 1, then R 1 is amino and R 2 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl; and provided that if c is 1 and d is 0, then R 2 is amino and R 1 is optionally substituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkyl, optionally substituted alkylalkoxy, optionally substituted alkylaryloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl.
• Design and evaluation of novel glutaminase inhibitors
  作者：Lee A. McDermott、Prema Iyer、Larry Vernetti、Shawn Rimer、Jingran Sun、Melissa Boby、Tianyi Yang、Michael Fioravanti、Jason O’Neill、Liwei Wang、Dylan Drakes、William Katt、Qingqiu Huang、Richard Cerione

  DOI：10.1016/j.bmc.2016.03.009

  日期：2016.4

  A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes. (C) 2016 Elsevier Ltd. All rights reserved.