2-cyano-N-[(1S)-1-phenylethyl]acetamide | 1240041-69-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-cyano-N-[(1S)-1-phenylethyl]acetamide
• CAS: 1240041-69-3
• 化学式: C₁₁H₁₂N₂O
• mdl: MFCD00456495
• 分子量: 188.229
• InChiKey: RZFUCBLCIHIKHV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-吡啶甲醛 、 2-cyano-N-[(1S)-1-phenylethyl]acetamide 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以87%的产率得到T5185090
  参考文献：
  名称：

  化学酶法路线酪氨酸磷酸化抑制剂1涉及苯乙胺的脂肪酶催化的动力学拆分与烷基氰基乙酸酯作为新的酰化剂

  摘要：

  乙基和异丙基氰基乙酸酯进行了测试，如外消旋的1-苯基乙胺的动力学拆分酰化剂外消旋- 1催化通过从脂肪酶B南极假丝酵母。最佳的转换高对映选择性合并，用氰基乙酸乙酯实现图2a作为酰化剂和固定化脂肪酶从乙南极假丝酵母（钙LB N435）作为生物催化剂。酰胺类（对映体- [R ）- 3及（小号- ）3通过脂肪酶催化的动力学拆分和由残留的化学转化（具有高对映体纯度（ee值> 98％），得到小号） -1，分别。酰胺用各种芳族醛反应4A - Ç，ê在Knoevenagel缩合，得到酪氨酸磷酸化抑制剂外消旋-图5a - Ç，ê，（- [R ）- 5A - Ç，È和（小号） -图5a - Ç，ê，被测试作为蛋白酪氨酸激酶上的人类癌症抑制剂细胞系HCT 116，A549，PC9，PC9ER，的Jurkat和MV4-11。虽然一些新颖酪氨酸磷酸化抑制剂的表现出弱的生物活性（EC 50 〜6-60μM），没有一个

  DOI：

  10.1016/j.tetasy.2015.04.013
• 作为产物：
  描述：

  α-苯乙胺 在 Novozym, lipase B from Candida antarctica, recombinant, expressed in Aspergillus niger, adsorbed on acrylic resin 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 96.0h， 生成 2-cyano-N-[(1S)-1-phenylethyl]acetamide
  参考文献：
  名称：

  化学酶法路线酪氨酸磷酸化抑制剂1涉及苯乙胺的脂肪酶催化的动力学拆分与烷基氰基乙酸酯作为新的酰化剂

  摘要：

  乙基和异丙基氰基乙酸酯进行了测试，如外消旋的1-苯基乙胺的动力学拆分酰化剂外消旋- 1催化通过从脂肪酶B南极假丝酵母。最佳的转换高对映选择性合并，用氰基乙酸乙酯实现图2a作为酰化剂和固定化脂肪酶从乙南极假丝酵母（钙LB N435）作为生物催化剂。酰胺类（对映体- [R ）- 3及（小号- ）3通过脂肪酶催化的动力学拆分和由残留的化学转化（具有高对映体纯度（ee值> 98％），得到小号） -1，分别。酰胺用各种芳族醛反应4A - Ç，ê在Knoevenagel缩合，得到酪氨酸磷酸化抑制剂外消旋-图5a - Ç，ê，（- [R ）- 5A - Ç，È和（小号） -图5a - Ç，ê，被测试作为蛋白酪氨酸激酶上的人类癌症抑制剂细胞系HCT 116，A549，PC9，PC9ER，的Jurkat和MV4-11。虽然一些新颖酪氨酸磷酸化抑制剂的表现出弱的生物活性（EC 50 〜6-60μM），没有一个

  DOI：

  10.1016/j.tetasy.2015.04.013

文献信息

• [EN] NOVEL ARGINASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS D'ARGINASE
  申请人：UNIV GRONINGEN

  公开号：WO2020249821A1

  公开（公告）日：2020-12-17

  The present invention relates to novel arginase inhibitors of formula (I). These novel compounds are useful in the treatment of diseases that are associated with arginase activity, such as asthma, allergic rhinitis and COPD (chronic obstructive pulmonary disease).

  本发明涉及式(I)的新型精氨酸酶抑制剂。这些新型化合物在治疗与精氨酸酶活性相关的疾病方面具有用途，如哮喘、过敏性鼻炎和慢性阻塞性肺疾病（COPD）。
• Preclinical Characterization of Signal Transducer and Activator of Transcription 3 Small Molecule Inhibitors for Primary and Metastatic Brain Cancer Therapy
  作者：Hikmat H. Assi、Chris Paran、Nathan VanderVeen、Jonathan Savakus、Robert Doherty、Emanuele Petruzzella、James D. Hoeschele、Henry Appelman、Leda Raptis、Tom Mikkelsen、Pedro R. Lowenstein、Maria G. Castro

  DOI：10.1124/jpet.114.214619

  日期：2014.6

  Signal transducer and activator of transcription 3 (STAT3) has been implicated as a hub for multiple oncogenic pathways. The constitutive activation of STAT3 is present in several cancers, including gliomas (GBMs), and is associated with poor therapeutic responses. Phosphorylation of STAT3 triggers its dimerization and nuclear transport, where it promotes the transcription of genes that stimulate tumor growth. In light of this role, inhibitors of the STAT3 pathway are attractive therapeutic targets for cancer. To this end, we evaluated the STAT3-inhibitory activities of three compounds (CPA-7 [trichloronitritodiammineplatinum(IV)], WP1066 [( S , E )-3-(6-bromopyridin-2-yl)-2-cyano- N -(1-phenylethyl)acrylamide, C17H14BrN3O], and ML116 [4-benzyl-1-thieno[2,3-d]pyrimidin-4-yl}piperidine, C18H19N3S]) in cultured rodent and human glioma cells, including GBM cancer stem cells. Our results demonstrate a potent induction of growth arrest in GBM cells after drug treatment with a concomitant induction of cell death. Although these compounds were effective at inhibiting STAT3 phosphorylation, they also displayed variable dose-dependent inhibition of STAT1, STAT5, and nuclear factor κ light-chain enhancer of activated B cells. The therapeutic efficacy of these compounds was further evaluated in peripheral and intracranial mouse tumor models. Whereas CPA-7 elicited regression of peripheral tumors, both melanoma and GBM, its efficacy was not evident when the tumors were implanted within the brain. Our data suggest poor permeability of this compound to tumors located within the central nervous system. WP1066 and ML116 exhibited poor in vivo efficacy. In summary, CPA-7 constitutes a powerful anticancer agent in models of peripheral solid cancers. Our data strongly support further development of CPA-7–derived compounds with increased permeability to enhance their efficacy in primary and metastatic brain tumors.

  信号转导子和转录激活子 3 (STAT3) 被认为是多种致癌途径的枢纽。 STAT3 的组成型激活存在于多种癌症中，包括神经胶质瘤 (GBM)，并且与不良治疗反应相关。 STAT3 的磷酸化会触发其二聚化和核运输，从而促进刺激肿瘤生长的基因转录。鉴于这一作用，STAT3 通路抑制剂是有吸引力的癌症治疗靶点。为此，我们评估了三种化合物（CPA-7 [三氯亚硝基二氨铂（IV）]、WP1066 [( S , E )-3-(6-bromopyridin-2-yl)-2-cyano- N培养的啮齿动物和人类神经胶质瘤细胞（包括 GBM）中的 -(1-苯乙基)丙烯酰胺，C17H14BrN3O] 和 ML116 [4-benzyl-1-噻吩并[2,3-d]嘧啶-4-基}哌啶，C18H19N3S])癌症干细胞。我们的结果表明，药物治疗后可有效诱导 GBM 细胞生长停滞，同时诱导细胞死亡。尽管这些化合物能有效抑制 STAT3 磷酸化，但它们也对活化 B 细胞的 STAT1、STAT5 和核因子 κ 轻链增强子表现出不同的剂量依赖性抑制作用。这些化合物的治疗功效在外周和颅内小鼠肿瘤模型中得到了进一步评估。尽管 CPA-7 能引起周围肿瘤（黑色素瘤和 GBM）消退，但当肿瘤植入脑内时，其功效并不明显。我们的数据表明该化合物对中枢神经系统内肿瘤的渗透性较差。 WP1066和ML116表现出较差的体内功效。总之，CPA-7 在外周实体癌模型中构成了强大的抗癌剂。我们的数据强烈支持进一步开发具有增加渗透性的 CPA-7 衍生化合物，以增强其对原发性和转移性脑肿瘤的疗效。
• Degrasyn-like symmetrical compounds: Possible therapeutic agents for multiple myeloma (MM-I)
  作者：Zhenghong Peng、David S. Maxwell、Duoli Sun、Basvoju A. Bhanu Prasad、Paul T. Schuber、Ashutosh Pal、Yunming Ying、Dongmei Han、Liwei Gao、Shimei Wang、Alexander Levitzki、Vaibhav Kapuria、Moshe Talpaz、Matthew Young、Hollis D. Showalter、Nicholas J. Donato、William G. Bornmann

  DOI：10.1016/j.bmc.2013.12.048

  日期：2014.2

  A series of degrasyn-like symmetrical compounds have been designed, synthesized, and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma) cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar potency against these tumor cells in comparison to degrasyn and inhibited Usp9x activity in vitro and in intact cells. These observations suggest that this new class of compounds holds promise as cancer therapeutic agents. (C) 2014 Published by Elsevier Ltd.
• Tyrphostin-like compounds with ubiquitin modulatory activity as possible therapeutic agents for multiple myeloma
  作者：Zhenghong Peng、Ashutosh Pal、Dongmei Han、Shimei Wang、David Maxwell、Alexander Levitzki、Moshe Talpaz、Nicholas J. Donato、William Bornmann

  DOI：10.1016/j.bmc.2011.09.057

  日期：2011.12

  With the goal of developing small molecules as novel regulators of signal transduction and apoptosis, a series of tyrphostin-like compounds were synthesized and screened for their activity against MM-1 (multiple myeloma) cells and other cell lines representing this malignancy. Synthesis was completed in solution-phase initially and then adopted to solid-phase for generating a more diverse set of compounds. A positive correlation was noted between compounds capable of inducing apoptosis and their modulation of protein ubiquitination. Further analysis suggested that ubiquitin modulation occurs through inhibition of cellular deubiquitinase activity. Bulky groups on the sidechain near the alpha,beta-unsaturated ketone caused a complete loss of activity, whereas cyclization on the opposite side was tolerated. Theoretical calculations at the B3LYP/LACV3P** level were completed on each molecule, and the resulting molecular orbitals and Fukui reactivity values for C(beta) carbon were utilized in developing a model to explain the compound activity. (C) 2011 Elsevier Ltd. All rights reserved.
• US7998986B2
  申请人：——

  公开号：US7998986B2

  公开（公告）日：2011-08-16