乙酰胺,N-(6-溴-2,3-二氢-3-羰基-1H-茚-5-基)- | 170456-57-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 中文名称: 乙酰胺,N-(6-溴-2,3-二氢-3-羰基-1H-茚-5-基)-
• 英文名称: 6-acetamido-5-bromo-1-indanone
• 英文别名: 6-acetylamino-5-bromo-1-indanone；5-acetamido-6-bromoindan-1-one；Acetamide, N-(6-bromo-2,3-dihydro-3-oxo-1H-inden-5-yl)-；N-(6-bromo-3-oxo-1,2-dihydroinden-5-yl)acetamide
• CAS: 170456-57-2
• 化学式: C₁₁H₁₀BrNO₂
• 分子量: 268.11
• InChiKey: QXKFCOLJFYLSIC-UHFFFAOYSA-N

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：
  0.27
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N1-(2,3-二氢-1H-茚-5-基)乙酰胺 在 chromium(VI) oxide 、 溴 、 溶剂黄146 作用下， 反应 0.5h， 生成 乙酰胺,N-(6-溴-2,3-二氢-3-羰基-1H-茚-5-基)-
  参考文献：
  名称：

  Cyclooxygenase-2 Inhibitors. Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives

  摘要：

  The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing nonsteroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)thio]-5-methanesulfonamido-1-indanone (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted B-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t(1/2) in squirrel monkeys, and seems less ulcergenic than 2 in rats.

  DOI：

  10.1021/jm00025a007

文献信息

• Antifolate chemistry: synthesis of 4-{N-[(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid via a (propargyl)Co2(CO)6+ complex
  作者：Vassilios Bavetsias、Rainer Clauss、Elisa A. Henderson

  DOI：10.1039/b301989f

  日期：——

  A new route to compound 3 (4-[N-(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino]benzoic acid), a crucial intermediate for the synthesis of potent inhibitors of thymidylate synthase (TS), is described. In this sequence the C6-N10 bond was constructed first, by the reductive amination of 5-acetamido-6-bromoindan-1-one 6 with tert-butyl 4-aminobenzoate, then

  化合物3（4- [N-（6RS）-2-甲基-4-氧代-3,4,7,8-四氢-6H-环戊[g]喹唑啉-6-基] -N-（描述了丙-2-炔基）氨基]苯甲酸（丙-2-炔基）氨基]苯甲酸）的重要中间体。在该序列中，首先通过用4-氨基苯甲酸叔丁酯对5-乙酰氨基-6-溴茚满-1-一6进行还原胺化反应来构建C6-N10键，然后形成环戊[g]喹唑啉酮环并生成炔丙基使用（炔丙基）Co 2（CO）6+络合物作为亲电炔丙基试剂，在N10位引入基团。
• [EN] PROCESS FOR THE PREPARATION OF CYCLOPENTA[g]QUINAZOLINE DERIVATIVES<br/>[FR] PROCEDE DE SYNTHESE
  申请人：BTG INT LTD

  公开号：WO2003020706A1

  公开（公告）日：2003-03-13

  Cyclopenta[g]quinazolines of formula (I), and esters and amides thereof may be made by reacting an ester or amide of formula (II), or a protected derivative thereof with a complex containing the (propargyl)Co2(CO)6+ion.

  公式(I)的环戊基[g]喹唑啉，以及其酯和酰胺可以通过将公式(II)的酯或酰胺或其保护衍生物与含有(propargyl)Co2(CO)6+离子的配合物反应而制得。
• [EN] ANTI-CANCER CYCLOPENTA[G]QUINAZOLINE COMPOUNDS<br/>[FR] COMPOSES DE CYCLOPENTA[G]QUINAZOLINE ANTICANCEREUX
  申请人：BTG INT LTD

  公开号：WO2003020748A1

  公开（公告）日：2003-03-13

  Cyclopenta[g]quinazolines of the formula (I):- wherein: A is a group OR or NR0R1 wherein R?0 and R1¿ are each independently hydrogen C¿l-4? alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or Cl-4 cyanoalkyl, or R?0 and R1¿ together with the intermediate N form a five- or six-membered heterocyclic ring; p is an integer in the range 1 to 4; R2 is hydrogen, C¿1-4? alkyl, C3-4 alkenyl, C3-4 alkynyl, C2-4 hydroxyalkyl, C2-4 halogenoalkyl or Cl-4 cyanoalkyl; Ar?l¿ is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C¿l-4? alkyl and Cl-4 alkoxy; and R?3¿ is a group of one of the following formulae: -A?1-Ar2-A2-Y1 -A5¿-CON(R)CH(Y?4)Y5 -A8-X-Ar4¿ and pharmaceutically acceptable salts or esters thereof are of therapeutic value particularly in the treatment of cancer.

  式(I)的环戊- [g]喹唑啉：其中：A是OR或NR0R1基团，其中R?0和R1¿各自独立地为氢，C¿l-4?烷基，C3-4烯基，C3-4炔基，C2-4羟基烷基，C2-4卤代烷基或Cl-4氰基烷基，或者R?0和R1¿与中间的N一起形成一个五元或六元杂环；p是1至4之间的整数；R2是氢，C¿1-4?烷基，C3-4烯基，C3-4炔基，C2-4羟基烷基，C2-4卤代烷基或Cl-4氰基烷基；Ar?l¿是苯撑，噻吩二基，噻唑二基，吡啶二基或嘧啶二基，可以选择地带有一个或两个取代基，所选取代基为卤代，羟基，氨基，硝基，氰基，三氟甲基，C¿l-4?烷基和Cl-4烷氧基；R?3¿是以下公式之一的基团：-A?1-Ar2-A2-Y1，-A5¿-CON(R)CH(Y?4)Y5，-A8-X-Ar4¿以及其药学上可接受的盐或酯，在癌症治疗中具有治疗价值。
• Anti-cancer cyclopenta (g)quinazoline compounds
  申请人：——

  公开号：US20040242606A1

  公开（公告）日：2004-12-02

  Cyclopenta[g]quinazolines of the formula (I):- wherein: A is a group OR or NR 0 R 1 wherein R 0 and R 1 are each independently hydrogen C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 2-4 hydroxyalkyl, C 2-4 halogenoalkyl or C 1-4 cyanoalkyl, or R 0 and R 1 together with the intermediate N form a five- or six-membered heterocyclic ring, p is an integer in the range 1 to 4, R 2 is hydrogen, C 1-4 alkyl, C 3-4 alkenyl, C 3-4 alkynyl, C 2-4 hydroxyalkyl, C 2-4 halogenoalkyl or C 1-4 cyanoalkyl; Ar 1 is phenylene, thiophenediyl, thiazolediyl, pyridinediyl or pyrimidinediyl which may optionally bear one or two substituents selected from halogeno, hydroxy, amino, nitro, cyano, trifluoromethyl, C 1-4 alkyl and C 1-4 alkoxy, and R 3 is a group of one of the following formulae: -A 1 -Ar 2 -A 2 -Y 1 -A 5 -CON(R)CH(Y 4 )Y 5 -A 8 -X—Ar 4 and pharmaceutically acceptable salts or esters thereof are of therapeutic value particularly in the treatment of cancer. 1

  公式（I）的环戊[g]喹唑啉：其中：A是OR或NR0R1基团，其中R0和R1各自独立地为氢、C1-4烷基、C3-4烯基、C3-4炔基、C2-4羟基烷基、C2-4卤代烷基或C1-4氰基烷基，或者R0和R1与中间的N一起形成五元或六元杂环；P是1至4范围内的整数，R2是氢、C1-4烷基、C3-4烯基、C3-4炔基、C2-4羟基烷基、C2-4卤代烷基或C1-4氰基烷基；Ar1是苯基、噻吩基、噻唑基、吡啶基或嘧啶基，其中可以选择带有卤素、羟基、氨基、硝基、氰基、三氟甲基、C1-4烷基和C1-4烷氧基的一个或两个取代基；R3是下列式中的一种基团：-A1-Ar2-A2-Y1-A5-CON(R)CH(Y4)Y5-A8-X—Ar4及其药学上可接受的盐或酯在治疗癌症方面具有治疗价值。
• Process for the preparation of cyclopenta[g]quinazoline derivatives
  申请人：——

  公开号：US20040266798A1

  公开（公告）日：2004-12-30

  Cyclopenta[g]quinazolines of formula (I), and esters and arnides thereof may be made by reacting an ester or amide of formula (II); or a protected derivative thereof with a complex containing the (propargyl)Co 2 (CO) 6 + ion. 1

  公式（I）的环戊[g]喹唑啉及其酯和酰胺可以通过将公式（II）的酯或酰胺或其保护衍生物与含（丙炔基）Co2（CO）6+离子的配合物反应而制得。