1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea | 1116743-47-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea
• 英文别名: 1-(2-Morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea；1-(2-morpholin-4-ylethyl)-3-(6-sulfanyl-1,3-benzothiazol-2-yl)urea
• CAS: 1116743-47-5
• 化学式: C₁₄H₁₈N₄O₂S₂
• 分子量: 338.455
• InChiKey: KZLFKBSRGMYSGY-UHFFFAOYSA-N

物化性质

• 密度：
  1.399±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  95.7
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea 在 吡啶 、 potassium carbonate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 48.2h， 生成 phenyl [6-(imidazo[1,2-a]pyrimidin-3-ylsulphanyl)-1,3-benzothiazol-2-yl]carbamate
  参考文献：
  名称：

  NOVEL IMIDAZO[1,2-a]PYRIMIDINE DERIVATIVES, METHOD FOR THE PREPARATION THEREOF, USE THEREOF AS MEDICAMENTS, PHARMACEUTICAL COMPOSITIONS AND NOVEL USE, IN PARTICULAR AS MET INHIBITORS

  摘要：

  该披露涉及公式(I)的咪唑[1,2-a]嘧啶衍生物及其同分异构体和药用盐。还披露了制备这些化合物的方法、药物组合物和治疗方法。

  公开号：

  US20110263593A1
• 作为产物：
  描述：

  N-(2-氨基乙基)吗啉 在 potassium dihydrogenphosphate 、 1,4-dithio-D,L-threitol 、 水 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 42.0h， 生成 1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea
  参考文献：
  名称：

  NOVEL IMIDAZO[1,2-a]PYRIMIDINE DERIVATIVES, METHOD FOR THE PREPARATION THEREOF, USE THEREOF AS MEDICAMENTS, PHARMACEUTICAL COMPOSITIONS AND NOVEL USE, IN PARTICULAR AS MET INHIBITORS

  摘要：

  该披露涉及公式(I)的咪唑[1,2-a]嘧啶衍生物及其同分异构体和药用盐。还披露了制备这些化合物的方法、药物组合物和治疗方法。

  公开号：

  US20110263593A1
• 作为试剂：
  描述：

  2-{[(2-morpholin-4-ylethyl)carbamoyl]amino}-1,3-benzothiazol-6-yl thiocyanate 、 1,4-二巯基-2,3-丁二醇 在 potassium dihydrogenphosphate 1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea 作用下， 以633 mg of 1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea are thus obtained in the form of a white solid的产率得到1-(2-morpholin-4-ylethyl)-3-(6-sulphanyl-1,3-benzothiazol-2-yl)urea
  参考文献：
  名称：

  6-triazolopyridazine sulfanyl benzothiazole derivatives as MET inhibitors

  摘要：

  本公开涉及式(I)的化合物：其中，A，W，X和Ra如本公开所定义，以及其盐，以及包含该化合物的制药组合物，制备它们的过程以及它们作为药物的用途，特别是作为MET抑制剂。

  公开号：

  US08546393B2

文献信息

• NOVEL 6-TRIAZOLOPYRIDAZINESULFANYL BENZOTHIAZOLE AND BENZIMIDAZOLE DERIVATIVES, METHOD FOR PRODUCTION THEREOF AND APPLICATION AS MEDICAMENTS AND PHARMNACEUTICAL COMPOSITIONS AND NOVEL USE AS MET INHIBITORS
  申请人：ALBERT Eva

  公开号：US20100298315A1

  公开（公告）日：2010-11-25

  The disclosure relates to compounds of formula (I): wherein , A, W, X, and Ra are as defined in the disclosure, and salts thereof, and to pharmaceutical compositions comprising said compounds, to processes for preparing them, and to their use as medicaments, in particular as MET inhibitors.

  该公开涉及式(I)的化合物： 其中 ，A、W、X和Ra如公开所定义，并其盐，以及包含所述化合物的药物组合物，用于制备它们的方法，以及它们作为药物的用途，特别是作为MET抑制剂。
• NOVEL IMIDAZO[1,2-A]PYRIDINE DERIVATIVES, METHOD FOR THE PREPARATION THEREOF, USE THEREOF AS MEDICAMENTS, PHARMACEUTICAL COMPOSITIONS AND NOVEL USE IN PARTICULAR AS MET INHIBITORS
  申请人：Damour Dominique

  公开号：US20110257171A1

  公开（公告）日：2011-10-20

  The invention relates to the novel products of formula (I): in which: Ra is H, Hal, aryl or heteroaryl, which are optionally substituted; Rb is H, Rc, —COORc-CO-Rc or —CO—NRcRd; where Rc is alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, all optionally substituted; Rd is H, alk or cycloalkyl; these products being in all the isomer forms and the salts, as medicaments, in particular as MET inhibitors.

  这项发明涉及公式(I)的新型产品：其中：Ra为H、Hal、芳基或杂环芳基，可以是可选择取代的；Rb为H、Rc、—COORc-CO-Rc或—CO—NRcRd；其中Rc为烷基、环烷基、杂环烷基、芳基和杂环芳基，均可选择取代；Rd为H、烷基或环烷基；这些产品以所有异构体形式和盐形式存在，作为药物，特别是作为MET抑制剂。
• DERIVATIVES OF 6-(6-NH-SUBSTITUTED-TRIAZOLOPYRIDAZINE-SULFANYL) BENZOTHIAZOLES AND BENZIMIDAZOLES, PREPARATION THEREOF, USE THEREOF AS DRUGS, AND USE THEREOF AS MET INHIBITORS
  申请人：Bacque Eric

  公开号：US20120040987A1

  公开（公告）日：2012-02-16

  The invention relates to novel products of the formula (I) where: (II) is a single or double bond; Rb is a hydrogen or fluorine atom; Ra is a NH-Rc radical in which Rc is an optionally substituted heterocycloalkyl, aryl, heteroaryl or -alkylcycloalkyl radical; X is S, SO, or SO2; A is NH or S; W is H, alkyl, or COR with R being cycloalkyl; alkyl; alkoxy; O-phenyl; —O— (CH2)n-phenyl with n=1 to 4; or NR1R2 with R1 being H or alk and R2 is H, cycloalkyl or alkyl; or R1, R2 form a cycle together with N optionally containing O, S, N and/or NH; all of said radicals being optionally substituted; wherein said products can be in any isomer or salt form, and can be used as drugs, in particular as MET inhibitors.

  本发明涉及式(I)的新型产物，其中：(II)是单键或双键；Rb是氢或氟原子；Ra是NH-Rc基团，其中Rc是可选取代的杂环烷基、芳基、杂芳基或-烷基环烷基基团；X是S、SO或SO2；A是NH或S；W是H、烷基或COR，其中R是环烷基、烷基、烷氧基、O-苯基、-O-(CH2)n-苯基，其中n为1至4，或NR1R2，其中R1为H或烷基，R2为H、环烷基或烷基；或R1、R2与N一起形成含有O、S、N和/或NH的环；所述基团均可选取代；其中所述产物可以是任何异构体或盐形式，并可用作药物，特别是作为MET抑制剂。
• NOVEL 6-TRIAZOLOPYRIDAZINE SULFANYL BENZOTHIAZOLE DERIVATIVES AS MET INHIBITORS
  申请人：Albert Eva

  公开号：US20140005189A1

  公开（公告）日：2014-01-02

  The disclosure relates to compounds of formula (I): wherein , A, W, X, and Ra are as defined in the disclosure, and salts thereof, and to pharmaceutical compositions comprising said compounds, to processes for preparing them, and to their use as medicaments, in particular as MET inhibitors.

  本公开涉及式(I)的化合物：其中，A、W、X和Ra如本公开所定义的那样，以及其盐，以及包含所述化合物的制药组合物，制备它们的过程，以及它们作为药物的用途，特别是作为MET抑制剂的用途。
• Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-<i>b</i>]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844)
  作者：Antonio Ugolini、Mireille Kenigsberg、Alexey Rak、Francois Vallée、Jacques Houtmann、Maryse Lowinski、Cécile Capdevila、Jean Khider、Eva Albert、Nathalie Martinet、Conception Nemecek、Sandrine Grapinet、Eric Bacqué、Manfred Roesner、Christine Delaisi、Loreley Calvet、Fabrice Bonche、Dorothée Semiond、Coumaran Egile、Hélène Goulaouic、Laurent Schio

  DOI：10.1021/acs.jmedchem.6b00280

  日期：2016.8.11

  The HGF/MET pathway is frequently activated in a variety of cancer types. Several selective small molecule inhibitors of the MET kinase are currently in clinical evaluation, in particular for NSCLC, liver, and gastric cancer patients. We report herein the discovery of a series of triazolopyridazines that are selective inhibitors of wild-type (WT) MET kinase and several clinically relevant mutants. We provide insight into their mode of binding and report unprecedented crystal structures of the Y1230H variant. A multiparametric chemical optimization approach allowed the identification of compound 12 (SAR125844) as a development candidate. In this chemical series, absence of CYP3A4 inhibition was obtained at the expense of satisfactory oral absorption. Compound 12, a promising parenteral agent for the treatment of MET-dependent cancers, promoted sustained target engagement at tolerated doses in a human xenograft tumor model. Preclinical pharmacokinetics conducted in several species were predictive for the observed pharmacokinetic behavior of 12 in cancer patients.