rac-ethyl 5-sec-butyl-1,3-oxazole-4-carboxylate | 1249460-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: rac-ethyl 5-sec-butyl-1,3-oxazole-4-carboxylate
• 英文别名: Ethyl 5-butan-2-yl-1,3-oxazole-4-carboxylate
• CAS: 1249460-54-5
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: NTUYYOJTBSPTEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  rac-ethyl 5-sec-butyl-1,3-oxazole-4-carboxylate 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 19.0h， 生成 (3Z,6Z)-3-benzylidene-6-((5-sec-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione trifluoroacetate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure

  摘要：

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.

  DOI：

  10.1021/jm2009088
• 作为产物：
  描述：

  2-甲基丁酸 在 草酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 rac-ethyl 5-sec-butyl-1,3-oxazole-4-carboxylate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure

  摘要：

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.

  DOI：

  10.1021/jm2009088

文献信息

• [EN] SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS<br/>[FR] HYDANTOÏNAMIDES SUBSTITUÉS UTILISÉS EN TANT QU'ANTAGONISTES D'ADAMTS7
  申请人：BAYER AG

  公开号：WO2021094436A1

  公开（公告）日：2021-05-20

  The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, heteroaryl or phenyl; R2 is hydrogen, cyano, halogen, alkylsulfonyl, alkyl, cycloalkyl or alkoxy; R3, R4, R5, R6, R7 and R8 are independently hydrogen, halogen, alkyl or alkoxy; most groups being optionally substituted; with the proviso that at least one of R2, R3, R4 is H; X1, X2, X3, X4, X5 and X6 are independently N or C; with the proviso that in each ring maximal one X is N.

  本申请涉及式(I)所示的取代脒酰胺作为ADAMTS7拮抗剂，涉及它们的制备过程，以及它们单独或组合用于治疗或预防疾病，特别是心血管疾病，包括动脉粥样硬化、冠心病(CAD)、外周血管病(PAD)、动脉闭塞性疾病或血管成形术后的再狭窄。R1是氢、烷基、环烷基、杂环烷基、杂芳基或苯基；R2是氢、氰基、卤素、烷基亚磺酰基、烷基、环烷基或烷氧基；R3、R4、R5、R6、R7和R8独立的是氢、卤素、烷基或烷氧基；大多数基团可被选择性地取代；条件是至少R2、R3、R4中的一个为H；X1、X2、X3、X4、X5和X6独立的是N或C；条件是每个环中最多只有一个X是N。
• [EN] SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS<br/>[FR] HYDANTOINAMIDES SUBSTITUÉS EN TANT QU'ANTAGONISTES D'ADAMTS7
  申请人：BAYER AG

  公开号：WO2021094434A1

  公开（公告）日：2021-05-20

  The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl; R2 is hydrogen or alkyl; A is 5-membered heteroaryl; Z is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; all groups being optionally substituted.

  该申请涉及公式（I）的替代咪唑酰脲作为ADAMTS7拮抗剂，以及它们的制备方法，它们单独或与其他药物联合用于治疗或预防疾病，特别是心血管疾病，包括动脉粥样硬化、冠状动脉疾病（CAD）、外周血管疾病（PAD）、动脉闭塞病或血管成形术后再狭窄。R1为氢、烷基、环烷基、杂环烷基、5-至6-成员杂芳基或苯基；R2为氢或烷基；A为5-成员杂芳基；Z为6-至10-成员芳基或5-至10-成员杂芳基；所有基团均可选择性地被取代。
• SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS
  申请人：Bayer AG

  公开号：EP3822265A1

  公开（公告）日：2021-05-19

  The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R 1 is hydrogen, alkyl, cycloalkyl, 5- to 6-membered heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl; R 2 is hydrogen or alkyl; A is 5-membered heteroaryl; Z is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; all groups being optionally substituted.

  本申请涉及作为 ADAMTS7 拮抗剂的式 (I) 取代的 hydantoinamides，涉及其制备工艺、单独使用或联合使用以治疗或预防疾病，特别是心血管疾病，包括动脉粥样硬化、冠状动脉疾病 (CAD)、外周血管疾病 (PAD)、动脉闭塞性疾病或血管成形术后再狭窄。 R 1 是氢、烷基、环烷基、5 至 6 元杂环烷基、5 至 6 元杂芳基或苯基；R 2 是氢或烷基；A 是 5 元杂芳基；Z 是 6 至 10 元芳基或 5 至 10 元杂芳基；所有基团均可任选被取代。
• Synthesis and Structure–Activity Relationship Study of Antimicrotubule Agents Phenylahistin Derivatives with a Didehydropiperazine-2,5-dione Structure
  作者：Yuri Yamazaki、Koji Tanaka、Benjamin Nicholson、Gordafaried Deyanat-Yazdi、Barbara Potts、Tomoko Yoshida、Akiko Oda、Takayoshi Kitagawa、Sumie Orikasa、Yoshiaki Kiso、Hiroyuki Yasui、Miki Akamatsu、Takumi Chinen、Takeo Usui、Yuki Shinozaki、Fumika Yakushiji、Brian R. Miller、Saskia Neuteboom、Michael Palladino、Kaneo Kanoh、George Kenneth Lloyd、Yoshio Hayashi

  DOI：10.1021/jm2009088

  日期：2012.2.9

  Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with activity of 33 and 50 exhibited a lowest effective concentration The values of 33 and 50 were 5 and 10 times more potent than second-generation derivative with both vascular disrupting and a benzophenone in place of the phenyl group. The anti-HuVEC of 2 and 1 nM for microtubule depolymerization, respectively. that of CA-4, respectively. These derivatives could be a valuable cytotoxic activities.