methyl 2-chloro-3-<4-<2-(2-benzoxazolylmethylamino)ethoxy>benzene>propanoate | 153939-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: methyl 2-chloro-3-<4-<2-(2-benzoxazolylmethylamino)ethoxy>benzene>propanoate
• 英文别名: methyl 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-chloropropanoate；methyl 3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-chloropropanoate
• CAS: 153939-24-3
• 化学式: C₂₀H₂₁ClN₂O₄
• 分子量: 388.851
• InChiKey: CCNFURFASZUTNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-chloro-3-<4-<2-(2-benzoxazolylmethylamino)ethoxy>benzene>propanoate 在 ammonium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-chloropropanamide
  参考文献：
  名称：

  Heterocyclic compounds and their use in the treatment of Type-II diabetes

  摘要：

  一种具有以下结构的化合物：A.sup.1 --X--(CH.sub.2).sub.n --O--A.sup.2 --A.sup.3 --CO.R.sup.2 (I)或其互变异构体和/或其药学上可接受的盐，和/或其药学上可接受的溶剂，其中：A.sup.1代表取代或未取代的芳香杂环基团；A.sup.2代表具有三个可选取代基团的苯环；A.sup.3代表具有式--(CH.sub.2).sub.m --CHR.sup.1 --的基团，其中R.sup.1代表卤素原子或式S(O).sub.p A.sup.4的基团，其中A.sup.4代表氢、取代或未取代的烷基、芳基、芳基烷基、烷基羰基或芳香杂环基团，p代表零或整数1或2，m代表零或范围在1到5之间的整数，或A.sup.3代表具有式--CH.dbd.CR.sup.1 --的基团，其中R.sup.1如上定义；R.sup.2代表OR.sup.3，其中R.sup.3代表氢、烷基、芳基或芳基烷基，或R.sup.2代表--NR.sup.4 R.sup.5，其中R.sup.4和R.sup.5各自独立地代表氢或烷基，或R.sup.4和R.sup.5与它们连接的氮原子一起形成杂环环；X代表O、S或NR，其中R代表氢原子、烷基、酰基、芳基烷基，其中芳基可能是取代或未取代的，或取代或未取代的芳基；n代表范围在2到6之间的整数；一种制备这种化合物的方法，包括这种化合物的药物组合物和这种化合物及组合物在医学中的用途。

  公开号：

  US05589492A1
• 作为产物：
  描述：

  2-氯苯并恶唑 在 吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 methyl 2-chloro-3-<4-<2-(2-benzoxazolylmethylamino)ethoxy>benzene>propanoate
  参考文献：
  名称：

  [[.omega.-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents

  摘要：

  A series of [(ureidoethoxy)benzyl]-2,4-thiazolidinediones and [[(heterocyclylamino)alkoxy]-benzyl]-2,4-thiazolidinediones was synthesized from the corresponding aldehydes. Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045). The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies. Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 Bl/6 ob/ob mice. From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.

  DOI：

  10.1021/jm00049a017

文献信息

• Non thiazolidinedione antihyperglycaemic agents. 1: α-Heteroatom substituted β-phenylpropanoic acids
  作者：D.R. Buckle、B.C.C. Cantello、M.A. Cawthorne、P.J. Coyle、D.K. Dean、A. Faller、D. Haigh、R.M. Hindley、L.J. Jefcott、C.A. Lister、I.L. Pinto、H.K. Rami、D.G. Smith、S.A. Smith

  DOI：10.1016/0960-894x(96)00383-6

  日期：1996.9

  The 5-benzylthiazolidine-2,4-dione moiety of insulin sensitising antidiabetic agents can be replaced by a range of alpha-heteroatom functionalised beta-phenylpropanoic acids. alpha-Oxy-carboxylic acids show potent antidiabetic activity and one compound, the alpha-ethoxyacid 15 (SE 213068), is one of the mast potent antihyperglycaemic agents yet reported. Copyright (C) 1996 Elsevier Science Ltd
• HETEROCYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF TYPE II-DIABETES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0635007A1

  公开（公告）日：1995-01-25
• US5589492A
  申请人：——

  公开号：US5589492A

  公开（公告）日：1996-12-31
• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF TYPE II-DIABETES<br/>[FR] COMPOSES HETEROCYCLIQUES ET LEUR UTILISATION POUR LE TRAITEMENT DU DIABETE DU TYPE II
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1993021166A1

  公开（公告）日：1993-10-28

  (EN) A compound of the formula A1-X-(CH2)n-O-A2-A3-CO.R2 (I) or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; A2 represents a benzene ring having three optional substituents; A3 represents a moiety of formula -(CH2)m-CHR1- wherein R1 represents a halogen atom or a moiety of formula S(O)pA4 wherein A4 represents hydrogen, substituted or unsubstituted alkyl, aryl, aralkyl, alkylcarbonyl or an aromatic heterocyclyl group and p represents zero or an integer 1 or 2 and m represents zero or an integer in the range of from 1 to 5, or A3 represents a moiety of formula -CH=CR1- wherein R1 is as defined above; R2 represents OR3 wherein R3 represents hydrogen, alkyl, aryl or aralkyl, or R2 represents -NR4R5 wherein R4 and R5 each independently represent hydrogen or alkyl or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring; X represents O, S or NR wherein R represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; and n represents an integer in the range of from 2 to 6; a process for the preparation of such a compound, a pharmaceutical composition comprising such a compound and the use of such a compound and composition in medicine.(FR) L'invention concerne un composé de la formule A1-X-(CH2)n-O-A2-A3-CO.R2 (I); ou une forme tautomère de celui-ci et/ou un sel de celui-ci acceptable sur le plan pharmaceutique et/ou un solvate de celui-ci acceptable sur le plan pharmaceutique, où A1 représente un groupe hétérocyclyle aromatique, substitué ou non; A2 représente un noyau benzénique ayant, le cas échéant, trois substituants; A3 représente un groupe de la formule -(CH2)m-CHR1- où R1 représente un atome d'halogène ou un groupe de la formule S(O)pA4, où A4 représente un hydrogène, un groupe alkyle, aryle, aralkyle, alkylcarbonyle, ou hétérocyclyle aromatique substitué ou non, p représente le zéro ou le nombre entier 1 ou 2 et m représente le zéro ou un nombre entier compris entre 1 et 5, ou A3 représente un groupe de la formule -CH=CR1, où R1 est comme défini ci-dessus; R2 représente OR3 où R3 représente un hydrogène, un groupe alkyle, aryle ou aralkyle, ou R2 représente -NR4R5 où R4 et R5 constituent ensemble avec un atome d'azote auquel ils sont liés un groupe hétérocyclique; X représente O, S, ou NR où R représente un atome d'hydrogène, un groupe alkyle, acyle, ou aralkyle où le groupe aryle peut être substitué ou non, ou un groupe aryle substitué ou non; et n représente un nombre entier compris entre 2 et 6. L'invention concerne également un procédé pour la préparation d'un tel composé, une composition pharmaceutique le contenant et l'utilisation d'un tel composé ou d'une telle composition en médecine.
• [[.omega.-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents
  作者：Barrie C. C. Cantello、Michael A. Cawthorne、Graham P. Cottam、Peter T. Duff、David Haigh、Richard M. Hindley、Carolyn A. Lister、Stephen A. Smith、Peter L. Thurlby

  DOI：10.1021/jm00049a017

  日期：1994.11

  A series of [(ureidoethoxy)benzyl]-2,4-thiazolidinediones and [[(heterocyclylamino)alkoxy]-benzyl]-2,4-thiazolidinediones was synthesized from the corresponding aldehydes. Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045). The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies. Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 Bl/6 ob/ob mice. From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.