(2S)-2-amino-3-hydroxy-N-(2-phenylethyl)propanamide | 200400-20-0

• 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: (2S)-2-amino-3-hydroxy-N-(2-phenylethyl)propanamide
• CAS: 200400-20-0
• 化学式: C₁₁H₁₆N₂O₂
• 分子量: 208.26
• InChiKey: DHWHIPPMOQQJPC-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-hydroxy-N-(2-phenylethyl)propanamide 在 N-甲基吗啉 、 nickel(IV) oxide 、 4 A molecular sieve 、 potassium tert-butylate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 四氯化碳 、 N,N-二甲基甲酰胺 、 乙腈 、 苯 为溶剂， 反应 28.5h， 生成 (E)-7-[4-[4-[(Phenethylamino)carbonyl]-2-oxazolyl]phenyl]-7-(pyridin-3-yl)hept-6-enoic Acid
  参考文献：
  名称：

  Development of Dual-Acting Agents for Thromboxane Receptor Antagonism and Thromboxane Synthase Inhibition. 3. Synthesis and Biological Activities of Oxazolecarboxamide-Substituted ω-Phenyl-ω-(3-pyridyl)alkenoic Acid Derivatives and Related Compounds

  摘要：

  A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA(2) receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid (14) with K-d = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI(2) level, and absence of agonist activity.

  DOI：

  10.1021/jm980173n
• 作为产物：
  描述：

  ((S)-2-Hydroxy-1-phenethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2S)-2-amino-3-hydroxy-N-(2-phenylethyl)propanamide
  参考文献：
  名称：

  Development of Dual-Acting Agents for Thromboxane Receptor Antagonism and Thromboxane Synthase Inhibition. 3. Synthesis and Biological Activities of Oxazolecarboxamide-Substituted ω-Phenyl-ω-(3-pyridyl)alkenoic Acid Derivatives and Related Compounds

  摘要：

  A novel series of oxazolecarboxamide-substituted omega-phenyl-omega-(3-pyridyl)alkenoic acid derivatives was discovered as potent dual-acting agents to block the TXA(2) receptor and to inhibit the thromboxane synthase (TRA/TSI). Synthesis, structure-activity relationship (SAR), and in vitro and in vivo pharmacology of this series of compounds are described. Modification of the series revolved around the oxazole moiety to increase the hydrophilicity of the compounds and to correlate the biological activity with lipophilicity of the compounds. The most potent in the series was (E)-7-[4-[4-[[(4-cyclohexylbutyl)amino]carbonyl]-2-oxazolyl]phenyl]-7-(3-pyridyl)hept-6-enoic acid (14) with K-d = 9.9 +/- 0.4 nM for the thromboxane receptor antagonism and IC50 = 55.0 +/- 17.9 nM for thromboxane synthase inhibition. The compound 14 was a selective TRA/TSI which exhibited desirable characteristics for oral activity, "shunt" effect to elevate PGI(2) level, and absence of agonist activity.

  DOI：

  10.1021/jm980173n

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS ET MÉTHODES POUR LE TRAITEMENT DU CANCER
  申请人：CEDARS SINAI MEDICAL CENTER

  公开号：WO2019040647A1

  公开（公告）日：2019-02-28

  Provided herein are compositions and methods for treating, inhibiting and/or reducing the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in subjects in need thereof. The methods include providing an agent that inhibits expression or activity of ONECUT2 and administering a therapeutically effective amount of the agent so as to treat, inhibit and/or reduce the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in the subject.

  本文提供了用于治疗、抑制和/或减轻神经母细胞瘤、小细胞肺癌（SCLC）、大细胞神经内分泌癌（LCNEC）、大细胞癌（LCC）、鳞状细胞癌（SqCC）和/或腺癌（AC）的组合物和方法，适用于需要的受试者。该方法包括提供抑制ONECUT2表达或活性的药剂，并向受试者施用治疗有效量的药剂，以治疗、抑制和/或减轻神经母细胞瘤、小细胞肺癌（SCLC）、大细胞神经内分泌癌（LCNEC）、大细胞癌（LCC）、鳞状细胞癌（SqCC）和/或腺癌（AC）。
• Carbamoyl substituted oxazoles as thromboxane receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0811621A2

  公开（公告）日：1997-12-10

  This invention relates to carbamoyl substituted heterocycles which are ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring and which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as pharmaceutical formulations containing them, methods for their use, and processes and intermediates for their preparation.

  本发明涉及氨基甲酰基取代的杂环，这些杂环是ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物，在苯基环上带有氨基甲酰基取代的噁唑基或噁唑啉基，具有血栓素受体拮抗和/或血栓素合成酶抑制作用，还涉及含有这些杂环的药物制剂、使用方法以及制备这些杂环的工艺和中间体。
• Preparation of substituted alkenoic acids
  申请人：ELI LILLY AND COMPANY

  公开号：EP0816361A2

  公开（公告）日：1998-01-07

  This invention relates to a highly selective process for preparation of E-ω-phenyl-ω-(3-pyridyl)-ω-alkenoic acid derivatives bearing a carbamoyl substituted oxazolyl or oxazolinyl group on the phenyl ring which demonstrate utility for thromboxane receptor antagonism and/or thromboxane synthase inhibition, as well as to intermediates therefor.

  本发明涉及一种制备 E-ω-苯基-ω-(3-吡啶基)-ω-烯酸衍生物的高选择性工艺，该衍生物在苯基环上带有氨基甲酰基取代的噁唑基或噁唑啉基，可用于血栓素受体拮抗和/或血栓素合成酶抑制，本发明还涉及其中间体。
• Compositions and methods for treating cancer
  申请人：Cedars-Sinai Medical Center

  公开号：US10927070B2

  公开（公告）日：2021-02-23

  Provided herein are compositions and methods for treating, inhibiting and/or reducing the severity of cancer in subjects in need thereof. The methods include providing an agent that inhibits expression or activity of ONECUT2 and administering a therapeutically effective amount of the agent so as to treat, inhibit and/or reduce the severity of cancer in the subject.

  本文提供了用于治疗、抑制和/或减轻有需要的受试者癌症严重程度的组合物和方法。这些方法包括提供一种抑制 ONECUT2 表达或活性的制剂，并施用治疗有效量的该制剂，以治疗、抑制和/或降低受试者癌症的严重程度。
• COMPOSITIONS AND METHODS FOR TREATING CANCER
  申请人：Cedars-Sinai Medical Center

  公开号：US20200188373A1

  公开（公告）日：2020-06-18

  Provided herein are compositions and methods for treating, inhibiting and/or reducing the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in subjects in need thereof. The methods include providing an agent that inhibits expression or activity of ONECUT2 and administering a therapeutically effective amount of the agent so as to treat, inhibit and/or reduce the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in the subject.