<1S-(1α,2α,3α,4α)>-2-<<3-<4-<(pentylamino)carbonyl>-2-oxazolyl>-7-oxabicyclo<2.2.1>hept-2-yl>methyl>benzenepropanoic acid methyl ester | 142663-84-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: <1S-(1α,2α,3α,4α)>-2-<<3-<4-<(pentylamino)carbonyl>-2-oxazolyl>-7-oxabicyclo<2.2.1>hept-2-yl>methyl>benzenepropanoic acid methyl ester
• 英文别名: methyl 3-[2-[[(1S,2R,3S,4R)-3-[4-(pentylcarbamoyl)-1,3-oxazol-2-yl]-7-oxabicyclo[2.2.1]heptan-2-yl]methyl]phenyl]propanoate
• CAS: 142663-84-1
• 化学式: C₂₆H₃₄N₂O₅
• 分子量: 454.566
• InChiKey: AZYMEZDFBRMQIG-KZDDHRSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  90.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  <1S-(1α,2α,3α,4α)>-2-<<3-<4-<(pentylamino)carbonyl>-2-oxazolyl>-7-oxabicyclo<2.2.1>hept-2-yl>methyl>benzenepropanoic acid methyl ester 在 sodium hydroxide 、 HI 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成 伊非曲班
  参考文献：
  名称：

  Method for preparing 7-oxabicycloheptyl substituted oxazole amide

  摘要：

  本方法提供一种制备结构式为##STR1##（其中R为烷基）的噁唑中间体的方法，其中使用氧化剂如溴化亚铜、碱如1,8-二氮杂双环[5.4.0]十一烷（DBU）和非氢供体胺碱如六亚甲基四胺（HMTA）氧化结构式为##STR2##的噁唑啉。所得的噁唑可以水解成最终的抗血栓-抗血管痉挛化合物。

  公开号：

  US05281716A1
• 作为产物：
  描述：

  <1S-1α,2α,3α,4α>-2-<<3-(hydroxymethyl)-7-oxabicyclo<2.2.1>hept-2-yl>methyl>benzenepropanoic acid, methyl ester 在 palladium hydroxide - carbon chromium(VI) oxide 、 四氯化碳 、 草酰氯 、 硫酸 、 氢气 、 1-羟基苯并三唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 copper(ll) bromide 作用下， 以 二氯甲烷 、 氯仿 、 乙酸乙酯 、 丙酮 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 49.17h， 生成 <1S-(1α,2α,3α,4α)>-2-<<3-<4-<(pentylamino)carbonyl>-2-oxazolyl>-7-oxabicyclo<2.2.1>hept-2-yl>methyl>benzenepropanoic acid methyl ester
  参考文献：
  名称：

  Interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles. Highly potent, selective, and long-acting thromboxane A2 receptor antagonists

  摘要：

  A series of interphenylene 7-oxabicyclo[2.2.1]heptane oxazoles (2) were prepared and evaluated for their thromboxane (TxA2) antagonistic activity in vitro and duration of action in vivo. Examination of the carboxyl side chain indicated that the interphenylene ring substitution pattern and, to a lesser extent, chain length were important factors in determining TxA2 antagonistic potency. For the carboxyl side chain, ortho substitution, a single methylene spacer between the interphenylene and oxabicycloheptane rings, and a propionic acid side-chain length were determined to be optimal. With respect to the oxazole side chain a wide range of amide substituents with diverse structures and lipophilicities were compatible with potent antagonistic activity. Finally. an acidic functional group on the alpha-chain and a hydrogen bond acceptor on the 4-position of the oxazole ring were critical for potent activity. From the analogs prepared 42 {BMS-180,291: [(+)-1S-(1alpha,2alpha,3alpha,4alpha)]-2-[[3-[4-[(n-pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2.1]hept-2-yl]methyl]benzenepropanoic acid} was found to be a potent, selective, and orally-active TxA2 antagonist with a long duration of action and has been selected as a candidate for clinical development. In human platelet-rich plasma, 42 inhibited arachidonic acid (800 muM) and U-46,619 (10 muM) induced aggregation with I50 values of 7 and 21 nM, respectively. Radioligand binding studies of 42 with [H-3]-SQ 29,548 showed a K(d) value of 4.0 +/- 1.0 nM in human platelet membranes. Both in vitro and in vivo studies indicated 42 was devoid of direct agonistic activity. In vivo 42 (0.2 mg/kg, po) showed extended protection (T50 = 14.4 h) from U-46,619 (2 mg/kg, iv) induced death in mice, and a single oral dose of 42 (3 mg/kg) abolished U46,619-induced platelet aggregation ex vivo in African green monkeys for >24 h.

  DOI：

  10.1021/jm00062a013

文献信息

• Method for preparing 7-oxabicycloheptyl substituted oxazole amide
  申请人：Bristol-Myers Squibb Company

  公开号：US05281716A1

  公开（公告）日：1994-01-25

  A method is provided for preparing oxazole intermediates of the structure ##STR1## (wherein R is alkyl) wherein an oxazoline of the structure ##STR2## is oxidized employing an oxidizing agent such as cupric bromide, a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and a non-hydride donor amine base such as hexamethylenetetraamine (HMTA). The resulting oxazole may be hydrolyzed to the final anti-thrombotic - anti-vasospastic compounds.

  本方法提供一种制备结构式为##STR1##（其中R为烷基）的噁唑中间体的方法，其中使用氧化剂如溴化亚铜、碱如1,8-二氮杂双环[5.4.0]十一烷（DBU）和非氢供体胺碱如六亚甲基四胺（HMTA）氧化结构式为##STR2##的噁唑啉。所得的噁唑可以水解成最终的抗血栓-抗血管痉挛化合物。
• Method for preparing 7-oxabicycloheptyl substituted bromooxazole amide
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05260449A1

  公开（公告）日：1993-11-09

  A method is provided for preparing bromooxazole intermediates of the structure ##STR1## wherein a vinyl compound of the structure ##STR2## wherein X.sup.1 and X.sup.2 are independently H and Br, is treated with a metal halide such as cupric bromide, and a base such as 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU). The resulting bromooxazole may be hydrolyzed and hydrogenolyzed to the final anti-thrombotic-anti-vasospastic compounds.

  提供了一种制备结构为##STR1##的溴氧唑中间体的方法，其中结构为##STR2##的乙烯基化合物，其中X.sup.1和X.sup.2独立地为H和Br，经过金属卤化物（如溴化铜）和碱（如1,8-二氮杂双环[5.4.0]十一烯（DBU））处理。所得的溴氧唑可以水解和氢解为最终的抗血栓和抗血管痉挛化合物。
• Novel methods for syntheses of substituted oxazoles by cyclization of vinyl bromides
  作者：Jagabandhu Das、Joyce A. Reid、David R. Kronenthal、Janak Singh、Paul D. Pansegrau、Richard H. Mueller

  DOI：10.1016/s0040-4039(00)74756-3

  日期：1992.12

  Several methods for converting vinyl bromides and vinyl dibromides to oxazoles are described. Cyclization of vinyl bromide 6 with cesium carbonate in dioxane forms oxazole 7 while 6 is converted to the corresponding bromooxazole 12 by treatment with CuBr2/DBU.
• A “Bottom-Up” Approach to Process Development:  Application of Physicochemical Properties of Reaction Products toward the Development of Direct-Drop Processes
  作者：Chien-Kuang Chen、Ambarish K. Singh

  DOI：10.1021/op0102114

  日期：2001.9.1

  The "bottom-up" approach to development of direct-drop processes is a powerful, yet simple, strategy that every process chemist should consider for the development of efficient, cost-effective, and environmentally friendly processes. This approach is aided by a "parallel crystallization" technique, which allows for rapid identification of multiple solvent systems for the crystallization of the desired product using a minimal amount of material and solvent. This "bottom-up" approach is illustrated by several examples where the desired product is crystallized directly from the reaction mixture.
• Cupric bromide mediated oxidation of 4-carboxyoxazolines to the corresponding oxazoles
  作者：Joel C. Barrish、Janak Singh、Steven H. Spergel、Wen Ching Han、Thomas P. Kissick、David R. Kronenthal、Richard H. Mueller

  DOI：10.1021/jo00068a059

  日期：1993.7