Boc-D-4Aph(Fmoc)-OH | 114346-31-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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: Boc-D-4Aph(Fmoc)-OH
• 英文别名: Boc-(4-Fmoc-amino)-D-Phe-OH；N^α-Boc-4--D-phenylalanine；tert-butoxycarbonyl-[4-(9-fluorenylmethoxycarbonylamino)phenyl]-D-alanine；(R)-3-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)phenyl)-2-((tert-butoxycarbonyl)amino)propanoic acid；(R)-2-tert-butoxycarbonylamino-3-[4-(9H-fluoren-9-ylmethoxycarbonylamino)phenyl]propionic acid；N-tert-butyloxycarbonyl-D-4-(9-fluorenylmethoxycarbonyl)aminophenylalanine；Boc-(4-amino-Fmoc)-D-Phe-OH；Boc-d-phe(4-nhfmoc)-oh；(2R)-3-[4-(9H-fluoren-9-ylmethoxycarbonylamino)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 114346-31-5
• 化学式: C₂₉H₃₀N₂O₆
• 分子量: 502.567
• InChiKey: ZKSJJSOHPQQZHC-RUZDIDTESA-N

物化性质

• 沸点：
  671.0±55.0 °C(Predicted)
• 密度：
  1.280±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• WGK Germany：
  3
• 海关编码：
  29242990

反应信息

• 作为反应物：
  描述：

  Boc-D-4Aph(Fmoc)-OH 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 tert-butyl ((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diaza-1(1,4)-benzenacyclododecaphane-11-yl)carbamate
  参考文献：
  名称：

  Automated Design of Macrocycles for Therapeutic Applications: From Small Molecules to Peptides and Proteins

  摘要：

  Macrocycles and cyclic peptides are increasingly attractive therapeutic modalities as they often have improved affinity, are able to bind to extended protein surfaces, and otherwise have favorable properties. Macrocyclization of a known binder may stabilize its bioactive conformation and improve its metabolic stability, cell permeability, and in certain cases oral bioavailability. Herein, we present implementation and application of an approach that automatically generates, evaluates, and proposes cyclizations utilizing a library of well-established chemical reactions and reagents. Using the three-dimensional (3D) conformation of the linear molecule in complex with a target protein as the starting point, this approach identifies attachment points, generates linkers, evaluates their geometric compatibility, and ranks the resulting molecules with respect to their predicted conformational stability and interactions with the target protein. As we show here with prospective and retrospective case studies, this procedure can be applied for the macrocyclization of small molecules and peptides and even PROteolysis TArgeting Chimeras (PROTACs) and proteins.

  DOI：

  10.1021/acs.jmedchem.0c01500
• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 Boc-4-氨基-D-苯丙氨酸 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 Boc-D-4Aph(Fmoc)-OH
  参考文献：
  名称：

  Novel gonadotropin-releasing hormone antagonists: peptides incorporating modified N.omega.-cyanoguanidino moieties

  摘要：

  In order to minimize the deleterious effects of histamine release resulting from the administration to rats and humans of some potent gonadotropin-releasing hormone (GnRH) antagonists, various arginine residues were replaced with the less basic N-omega-cyano-N-omega'-alkyl- or -arylhomoarginine, -arginine, or -p-aminophenylalanine and N-omega-triazolyllysine, -ornithine or -p-aminophenylalanine residues in active analogues. These novel analogues were synthesized on a solid-phase support via a two-step modification of the N-omega-NH2 of lysine, ornithine, or p-aminophenylalanine residues in otherwise protected resin bound peptides. Most analogues were tested in the rat antiovulatory assay (AOA) and three in vitro assays: a pituitary cell culture assay, a binding assay to pituitary cell membranes, and a histamine release assay. Introduction of the cyanoguanidino and N-omega-triazolyl moieties into GnRH analogues yielded several water-soluble antagonists which showed a desirable therapeutic ratio (low histamine release activity to high in vivo potency). Among them, ''Azaline'' (10, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6(atz),ILys8,DAla10]GnRH), inhibited ovulation in the rat by 90% at 2-mu-g/rat with an ED50 in the in vitro histamine release assay comparable to that of GnRH itself.

  DOI：

  10.1021/jm00112a013

文献信息

• [EN] MACROCYCLIC COMPOUNDS FOR MODULATING IL-17<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR UNE MODULATION D'IL-17
  申请人：ENSEMBLE THERAPEUTICS CORP

  公开号：WO2013116682A1

  公开（公告）日：2013-08-08

  The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

  这项发明通常涉及公式I的大环化合物及其治疗用途。更具体地，该发明涉及调节IL-17活性的大环化合物，或者用于治疗炎症性疾病和其他与IL-17相关的疾病的大环化合物。
• MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIa
  申请人：Kallus Christopher

  公开号：US20110178130A1

  公开（公告）日：2011-07-21

  The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

  该发明涉及式(I)的化合物，这些化合物是激活的凝血酶可激活的纤溶抑制剂的抑制剂。式I的化合物适用于生产用于预防、次级预防和治疗与血栓形成、栓塞、高凝血性或纤维化变化相关的一个或多个疾病的药物。
• Iterative Approach to the Discovery of Novel Degarelix Analogues:  Substitutions at Positions 3, 7, and 8. Part II
  作者：Manoj P. Samant、Jozsef Gulyas、Doley J. Hong、Glenn Croston、Catherine Rivier、Jean Rivier

  DOI：10.1021/jm050134t

  日期：2005.7.1

  extent (efficacy and duration of action) of inhibition of luteinizing hormone (LH) release. Structurally, this series of analogues has novel substitutions at positions 3, 7, and 8 and N(alpha)-methylation at positions 6, 7, and 8 in the structure of degarelix. These substitutions were designed to probe the spatial limitations of the receptor's cavity and to map the steric and ionic boundaries. Some

  Degarelix（FE200486，Ac-d-2Nal（1）-d-4Cpa（2）-d-3Pal（3）-Ser（4）-4Aph（1-Hor）（5）-d-4Aph（Cbm）（6 ）-Leu（7）-ILys（8）-Pro（9）-d-Ala（10）-NH（2））是哺乳动物皮下给药后促性腺激素释放激素（GnRH）的强效且长效拮抗剂包括人类。在表达人GnRH受体的HEK-293细胞中，通过报告基因分析法合成，表征并表征了地加瑞克的类似物，并筛选了GnRH诱导的应答的拮抗作用。在去势雄性大鼠试验中还测定了作用的持续时间，以测量抑制黄体生成素（LH）释放的程度（作用和作用的持续时间）。从结构上讲，这一系列类似物在地加瑞克的结构中的3、7和8位具有新的取代基，并在6、7和8位具有Nα-甲基化。设计这些替代物以探测受体腔的空间限制并绘制空间和离子边界。引入了一些官能团，这些官能团被认为会影响类似物的药动学性
• MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIA
  申请人：Kallus Christopher

  公开号：US20140039011A1

  公开（公告）日：2014-02-06

  The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明涉及公式（I）的化合物，它们是活化的凝血酶-可激活纤溶抑制剂的抑制剂。公式I的化合物适用于生产预防、次级预防和治疗与血栓、栓塞、高凝状态或纤维化变化相关的一个或多个疾病的药物。
• MACROCYCLIC COMPOUNDS FOR MODULATING IL-17
  申请人：ENSEMBLE THERAPEUTICS CORPORATION

  公开号：US20150005319A1

  公开（公告）日：2015-01-01

  The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders.

  本发明涉及公式I的大环化合物及其治疗用途。更具体地，本发明涉及调节IL-17活性或用于治疗医疗情况（例如炎症性疾病和其他IL-17相关疾病）的大环化合物。