(3R,6R,9R)-2-Oxo-3-[N-(Fmoc)amino]-1-azabicyclo[4.3.0]-nonane-9-carboxylic acid

• 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: (3R,6R,9R)-2-Oxo-3-[N-(Fmoc)amino]-1-azabicyclo[4.3.0]-nonane-9-carboxylic acid
• 英文别名: (3R,6R,8aR)-6-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxo-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxylic acid
• 化学式: C₄₅H₅₆N₅O₇Pol
• 分子量: 420.5
• InChiKey: UYXMHFDJJRMKTP-XMDBHEJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,6R,9R)-2-Oxo-3-[N-(Fmoc)amino]-1-azabicyclo[4.3.0]-nonane-9-carboxylic acid 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 cyclopentyl N-[(2S)-1-[(2S,4R)-4-[2,6-bis(4-fluoroanilino)pyrimidin-4-yl]oxy-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Cytokine receptor modulators and uses thereof

  摘要：

  本发明涉及细胞因子受体结合化合物，例如非竞争性VEGF受体、IL-1受体、IL-4受体或IGF-1受体结合肽和肽类拟态拮抗剂，以及这些化合物的治疗用途。本发明的化合物可用于治疗细胞因子相关疾病，如增生性疾病（例如结肠、乳腺、前列腺和肺癌）、异常新血管生成和血管生成、年龄相关性黄斑变性以及增生性和/或炎症性皮肤疾病，如银屑病。

  公开号：

  US20090048161A1
• 作为产物：
  描述：

  (4R)-4-[[(3R,6R,8aR)-6-[[(2R)-2-[[(2R)-2,5-diaminopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxo-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carbonyl]amino]-5-[[(2R)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (3R,6R,9R)-2-Oxo-3-[N-(Fmoc)amino]-1-azabicyclo[4.3.0]-nonane-9-carboxylic acid
  参考文献：
  名称：

  Cytokine receptor modulators and uses thereof

  摘要：

  本发明涉及细胞因子受体结合化合物，例如非竞争性VEGF受体、IL-1受体、IL-4受体或IGF-1受体结合肽和肽类拟态拮抗剂，以及这些化合物的治疗用途。本发明的化合物可用于治疗细胞因子相关疾病，如增生性疾病（例如结肠、乳腺、前列腺和肺癌）、异常新血管生成和血管生成、年龄相关性黄斑变性以及增生性和/或炎症性皮肤疾病，如银屑病。

  公开号：

  US20090048161A1

文献信息

• Interleukin-1 receptor antagonists, compositions, and methods of treatment
  申请人：Chemtob Sylvain

  公开号：US20060094663A1

  公开（公告）日：2006-05-04

  Peptides that are designed to inhibit the biological activity of the IL-1R type 1 receptor and inhibit IL-1R/IL-1RacP related cell signaling and biological activity are disclosed. Compositions comprising IL-1R antagonists of the present invention are useful in the treatment of IL-1 related diseases or conditions such as arthritis, rheumatoid arthritis, osteoarthritis, and inflammatory bowel disease as well as other chronic or acute inflammatory diseases. This invention also discloses an isolated compound having an IL-1R antagonist activity, said compound being selected from the group consisting of: a peptide comprising the amino acid sequence RYTPELX, wherein R, Y, T, P, E, L, refer to their corresponding amino acids, and X is selected from no amino acid and alanine (A); and a derivative of (a) wherein the derivative incorporates one, two or three amino acid modification selected from an amino acid addition, deletion or substitution in the RYTPEL portion of the peptide, and wherein said derivative maintains its antagonist IL-1R activity.

  本发明揭示了设计用于抑制IL-1R类型1受体的生物活性并抑制IL-1R/IL-1RacP相关细胞信号传导和生物活性的肽。本发明的IL-1R拮抗剂组合物在治疗与IL-1相关的疾病或病况，如关节炎、类风湿性关节炎、骨关节炎和炎性肠病以及其他慢性或急性炎症性疾病方面非常有用。本发明还揭示了一种具有IL-1R拮抗剂活性的分离化合物，所述化合物选自以下组成的群体：包括氨基酸序列RYTPELX的肽，其中R、Y、T、P、E、L分别指它们对应的氨基酸，X选自无氨基酸和丙氨酸（A）；以及（a）的衍生物，该衍生物在肽的RYTPEL部分中包含一、二或三个氨基酸修饰，所选的修饰包括氨基酸添加、删除或替换，并且该衍生物保持其拮抗剂IL-1R活性。
• INTERLEUKIN-1 RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS OF TREATMENT
  申请人：Chemtob Sylvain

  公开号：US20100041609A1

  公开（公告）日：2010-02-18

  Peptides that are designed to inhibit the biological activity of the IL-1R type 1 receptor and inhibit IL-1R/IL-1RacP related cell signaling and biological activity are disclosed. Compositions comprising IL-1R antagonists of the present invention are useful in the treatment of IL-1 related diseases or conditions such as arthritis, rheumatoid arthritis, osteoarthritis, and inflammatory bowel disease as well as other chronic or acute inflammatory diseases. This invention also discloses an isolated compound having an IL-1R antagonist activity, said compound being selected from the group consisting of: a peptide comprising the amino acid sequence RYTPELX, wherein R, Y, T, P, E, L, refer to their corresponding amino acids, and X is selected from no amino acid and alanine (A); and a derivative of (a) wherein the derivative incorporates one, two or three amino acid modification selected from an amino acid addition, deletion or substitution in the RYTPEL portion of the peptide, and wherein said derivative maintains its antagonist IL-1R activity.

  本发明揭示了设计用于抑制IL-1R类型1受体的生物活性并抑制IL-1R/IL-1RacP相关细胞信号和生物活性的肽。包含本发明的IL-1R拮抗剂的组合物在治疗与IL-1相关的疾病或病况，如关节炎、类风湿性关节炎、骨关节炎和炎症性肠病以及其他慢性或急性炎症性疾病方面是有用的。本发明还揭示了一种具有IL-1R拮抗剂活性的分离化合物，所述化合物选自以下组：包含氨基酸序列RYTPELX的肽，其中R、Y、T、P、E、L分别指它们对应的氨基酸，X选自无氨基酸和丙氨酸（A）；及其衍生物，其中衍生物在肽的RYTPEL部分中包含一种、两种或三种氨基酸修饰，所述修饰选自氨基酸添加、删除或替换，并且所述衍生物保持其拮抗剂IL-1R活性。
• CYTOKINE RECEPTOR MODULATORS AND USES THEREOF
  申请人：Chemtob Sylvain

  公开号：US20110144014A1

  公开（公告）日：2011-06-16

  The present invention relates to cytokine receptor-binding compounds, such as non-competitive VEGF receptor, IL-1 receptor, IL-4 receptor, or IGF-1 receptor-binding peptides and petidomimetic antagonists, and therapeutic uses of such compounds. The compounds of the present invention may be used in the treatment of cytokine-associated diseases such as proliferative disorders (for example, colon, breast, prostate, and lung cancer), abnormal neovascularization and angiogenesis, age-related macular degeneration, and proliferative and/or inflammatory skin disorders such as psoriasis.

  本发明涉及细胞因子受体结合化合物，例如非竞争性VEGF受体、IL-1受体、IL-4受体或IGF-1受体结合肽和肽类拟拟物拮抗剂，以及这些化合物的治疗用途。本发明的化合物可用于治疗细胞因子相关疾病，如增生性疾病（例如结肠、乳腺、前列腺和肺癌）、异常新生血管和血管生成、年龄相关性黄斑变性和增生性和/或炎症性皮肤疾病，如银屑病。
• US8618054B2
  申请人：——

  公开号：US8618054B2

  公开（公告）日：2013-12-31
• [EN] PEPTIDOMIMETICS FOR MODULATING INTERLEUKIN-1 RECEPTOR<br/>[FR] PEPTIDOMIMÉTIQUES POUR MODULER LE RÉCEPTEUR D'INTERLEUKINE-1
  申请人：CT HOSPITALIER UNIVERSITAIRE S

  公开号：WO2010106441A2

  公开（公告）日：2010-09-23

  The present invention provides, among other things, improved Allosteramers™ for modulating IL-I receptor activity. In particular, the present invention provides peptidomimetics containing lactams and/or Bab residues. Pharmaceutical compositions of the peptidomimetic compounds of the present invention and methods of using these compositions in the treatment of various disorders are also provided.