5-甲基-2-(4-甲基-1-哌嗪)苯胺 | 946731-22-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5-甲基-2-(4-甲基-1-哌嗪)苯胺
• 英文名称: 2-(4-methylpiperazin-1-yl)-5-methylaniline
• 英文别名: 5-Methyl-2-(4-methyl-1-piperazinyl)aniline；5-methyl-2-(4-methylpiperazin-1-yl)aniline
• CAS: 946731-22-2
• 化学式: C₁₂H₁₉N₃
• mdl: MFCD10686569
• 分子量: 205.303
• InChiKey: MDPCCBRUVCKNEY-UHFFFAOYSA-N

物化性质

• 沸点：
  350.5±42.0 °C(Predicted)
• 密度：
  1.073±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-甲基-2-(4-甲基-1-哌嗪)苯胺 在 1-甲基吡咯烷 、 吡啶 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 N-(5-methyl-2-(4-methylpiperazin-1-yl)phenyl)-N'-(4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)urea
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468
• 作为产物：
  描述：

  4-氟-3-硝基甲苯 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 20.0~122.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 生成 5-甲基-2-(4-甲基-1-哌嗪)苯胺
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468

文献信息

• 8,9-DIHYDROIMIDAZOLE[1,2-A]PYRIMIDO[5,4-E]PYRIMIDINE-5(6H)-KETONE COMPOUND
  申请人：Impact Therapeutics, Inc

  公开号：EP3543242A1

  公开（公告）日：2019-09-25

  Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

  所公开的是 8,9-二氢咪唑并[1,2-a]嘧啶并[5,4-e]嘧啶-5(6H)-酮化合物，具体由式 I 表示： 或其药学上可接受的盐或原药，其中 A 和 R1-R7 在此定义。具有式 I 的化合物是 Wee1 激酶抑制剂。因此，本公开的化合物可用于治疗由 Wee1 活性异常引起的疾病。
• [EN] NOVEL ARYLPIPERAZINE DERIVED FROM PIPERIDINE AS ANTIDEPRESSANT MEDICINES<br/>[FR] NOUVELLES ARYLPIPERAZINES DERIVEES DE PIPERIDINE COMME MEDICAMENTS ANTIDEPRESSEURS
  申请人：PIERRE FABRE MEDICAMENT

  公开号：WO1998031669A1

  公开（公告）日：1998-07-23

  (EN) The invention concerns compounds of formula (I) in which in particular, R1 represents R'1, OR'1, SR'1, NHR'1, COR'1, CHOHR'1, CH2R'1, in which R'1 represents an aryl radical selected among a phenyl, a naphthyl or a pyridyl; R2 represents a halogen (Cl, F, Br), OH, NH2, CN, NO2, R'2, OR'2, SR'2, NHR'2, COR'2, CHOHR'2, COOR'2, NHCOR'2, NHCOOR'2, NHSO2R'2, OCONHR'2, in which R'2 represents an alkyl chain linear or branched, an aryl or an arylalkyl; Z represents CO-(CH2)n-O, CO-(CH2)n-NH, (CH2)m-O,(CH2)m-NH, CO-(CH2)p-CONH-, (CH2)p-CONH, CO-(CH2)p-NHCONH-, (CH2)m-NHCONH, -CO(CH2)p-OCONH-, (CH2)m-OCONH, -CO(CH2)p-NHCOO, (CH2)m-NHCOO, in which n represents zero or a whole number ranging between 1 and 8, m represents a whole number ranging between 2 and 8 and p represents a whole number ranging between 1 and 8; Ar represents an aromatic radical such as a phenyl or a naphthyl; R3 represents an alkyl radical linear or branched containing 1 to 6 carbon atoms: These compounds are particularly useful as antidepressant drugs.(FR) La présente invention concerne les composés de formule (I) dans laquelle notamment, R1 représente R'1, OR'1, SR'1, NHR'1, COR'1, CHOHR'1, CH2R'1, dans lesquels R'1 represente un reste aryle choisi parmi un phényle, un naphtyle ou un pyridyle; R2 représente un halogène (Cl, F, Br), OH, NH2, CN, NO2, R'2, OR'2, SR'2, NHR'2, COR'2, CHOHR'2, COOR'2, NHCOR'2, NHCOOR'2, NHSO2R'2, OCONHR'2, dans lesquels R'2 représente une chaîne alkyle linéaire ou ramifiée, un aryle ou un alkylaryle; Z représente CO-(CH2)n-O, CO-(CH2)n-NH, (CH2)m-O, (CH2)m-NH, CO-(CH2)p-CONH-, (CH2)p-CONH, CO-(CH2)p-NHCONH-, (CH2)m-NHCONH, -CO(CH2)p-OCONH-, (CH2)m-OCONH, -CO(CH2)p-NHCOO-, (CH2)m-NHCOO, dans lesquels n représente zéro ou un nombre entier compris entre 1 et 8, m représente un nombre entier compris entre 2 et 8 et p représente un nombre entier compris entre 1 et 8; Ar représente un radical aromatique tel qu'un phényle ou un naphtyle; R3 représente un radical alkyle linéaire ou ramifié comprenant de 1 à 6 atomes de carbone. Ces composés sont notamment utiles comme médicaments antidépresseurs.