(4-{[(9H-芴-9-基甲氧基)羰基]氨基}-1-哌啶基)乙酸

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (4-{[(9H-芴-9-基甲氧基)羰基]氨基}-1-哌啶基)乙酸
• 中文别名: (3S,5Z,7E)-1-氟-9,10-裂胆甾-5,7,10-三烯-3,25-二醇；FMOC-4-氨基-(1-羧甲基)哌啶
• 英文名称: Fmoc-4-amino-(1-carboxymethyl)piperidine
• 英文别名: Fmoc-Pip-OH；2-[4-(9H-fluoren-9-ylmethoxycarbonylamino)piperidin-1-ium-1-yl]acetate
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: VLQJIWJYRZIBMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-{[(9H-芴-9-基甲氧基)羰基]氨基}-1-哌啶基)乙酸 、 (1R)-2-(1H-indol-3-yl)-1-[4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-1,2,4-triazol-3-yl]ethanamine;hydrochloride 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Development of Nonpeptidic Inverse Agonists of the Ghrelin Receptor (GHSR) Based on the 1,2,4-Triazole Scaffold

  摘要：

  GHSR controls, among others, growth hormone and insulin secretion, adiposity, feeding, and glucose metabolism. Therefore, an inverse agonist ligand capable of selectively targeting GHSR and reducing its high constitutive activity appears to be a good candidate for the treatment of obesity-related metabolic diseases. In this context, we present a study that led to the development of several highly potent and selective inverse agonists of GHSR based on the 1,2,4-triazole scaffold. We demonstrate that, depending on the nature of the substituents on positions 3, 4, and 5, this scaffold leads to ligands that exert an intrinsic inverse agonist activity on GHSR-catalyzed G protein activation through the stabilization of a specific inactive receptor conformation. Thanks to an in vivo evaluation, we also show that one of the most promising ligands not only exerts an effect on insulin secretion in rat pancreatic islets but also affects the orexigenic effects of ghrelin in mice.

  DOI：

  10.1021/acs.jmedchem.9b02122
• 作为产物：
  描述：

  4-(Fmoc-氨基)哌啶 盐酸盐 、 溴乙酸 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 96.0h， 以37%的产率得到(4-{[(9H-芴-9-基甲氧基)羰基]氨基}-1-哌啶基)乙酸
  参考文献：
  名称：

  通过引入人工支架提高肽放射性示踪剂的稳定性：哪种结构元素最有用？

  摘要：

  肽类放射性示踪剂是使用单光子发射计算机断层扫描和正电子发射断层扫描对各种生物靶标进行特定体内成像的高效物质。然而，一些放射性标记的肽（如铃蟾肽类似物）仅表现出有限的稳定性，阻碍了成功的目标可视化。对放射性标记肽的稳定性产生积极影响的一种选择是引入某些人工分子支架。为了比较评估不同结构元素对放射性标记肽稳定性的影响，并确定那些对肽放射性示踪剂稳定最有用的结构元素，合成了几种单体和二聚体铃蟾肽衍生物，表现出不同的分子设计和螯合剂 NODAGA（ 68) Ga 标记。评估放射性标记肽在人血清中的体外稳定性，以确定引入的分子支架对肽血清稳定性的影响。评估结果表明，支架结构的引入和整体分子设计对所得肽放射性示踪剂的稳定性有重大影响。但是，除了使用某些支架结构发现的一些普遍趋势之外，获得的结果还表明有必要根据经验评估它们对每个易感肽放射性示踪剂的稳定性的影响。评估结果表明，支架结构的引入和整体分子设计

  DOI：

  10.1002/jlcr.3315

文献信息

• [EN] NOVEL RADIOLABELLED CXCR4-TARGETING COMPOUNDS FOR DIAGNOSIS AND THERAPY<br/>[FR] NOUVEAUX COMPOSÉS RADIOMARQUÉS DIAGNOSTIQUES ET THÉRAPEUTIQUES CIBLANT CXCR4
  申请人：PROVINCIAL HEALTH SERVICES AUTHORITY

  公开号：WO2020210919A1

  公开（公告）日：2020-10-22

  This application relates to compounds of Formula (I): [targeting peptide]-N(R1)-X1(R2)L1-[linker]-RX n1 (I). The targeting peptide is cyclo[L-Phe-L-Tyr-L-Lys(iPr)-D-Arg-L-2-Nal-Gly-D-Glu]-L-Lys(iPr). R1 is H or methyl. X1 is an optionally substituted C1-C15 hydrocarbon optionally comprising heteroatoms. R2 is C(O)OH or C(O)NH2. L1 is a linkage (thiolether, amide, maleimide-thiol, triazole). The linker has a net negative charge at physiological pH and is a linear or branched chain of 1-10 units of X2L2 and/or X2(L2)2, wherein: each X2 is, independently, an optionally substituted C1-C15 hydrocarbon optionally comprising heteroatoms; and each L2 is a linkage. The linker optionally further comprises an albumin binder bonded to an L2. Each RX is a radiolabelling group linked through a separate L2, selected from: a metal chelator; a prosthetic group containing trifluoroborate (BF3); or a prosthetic group containing a silicon-fluorine-acceptor moiety. The compounds may be useful for imaging CXCR4-expressing tissues or for treating CXCR4-associated diseases or conditions (e.g. cancer).

  这个应用涉及到Formula (I)的化合物：[靶向肽]-N(R1)-X1(R2)L1-[连接物]-RX n1 (I)。靶向肽是cyclo[L-Phe-L-Tyr-L-Lys(iPr)-D-Arg-L-2-Nal-Gly-D-Glu]-L-Lys(iPr)。R1是H或甲基。X1是一个可选择地取代的含有杂原子的C1-C15烃。R2是C(O)OH或C(O)NH2。L1是一个连接物（硫醚、酰胺、马来酰亚胺-硫醇、三唑）。连接物在生理pH下具有净负电荷，是由1-10个X2L2和/或X2(L2)2的线性或支链构成，其中：每个X2独立地是一个可选择地取代的含有杂原子的C1-C15烃；每个L2是一个连接物。连接物可选择地进一步包括与L2结合的白蛋白结合剂。每个RX是通过单独的L2连接的放射标记基团，选自：金属螯合剂；含三氟硼酸盐（BF3）的假体基团；或含硅-氟受体基团的假体基团。这些化合物可能对于成像CXCR4表达组织或治疗与CXCR4相关的疾病或症状（如癌症）有用。
• [EN] RADIOLABELED BOMBESIN-DERIVED COMPOUNDS FOR IN VIVO IMAGING OF GASTRIN-RELEASING PEPTIDE RECEPTOR (GRPR) AND TREATMENT OF GRPR-RELATED DISORDERS<br/>[FR] COMPOSÉS RADIOMARQUÉS DÉRIVÉS DE LA BOMBÉSINE POUR L'IMAGERIE IN VIVO DU RÉCEPTEUR DU PEPTIDE LIBÉRANT DE LA GASTRINE (GRPR) ET TRAITEMENT DES TROUBLES LIÉS AU GRPR
  申请人：PROVINCIAL HEALTH SERVICES AUTHORITY

  公开号：WO2021068051A1

  公开（公告）日：2021-04-15

  There is provided bombesin-derived compounds of Formula Ia (RX-L-Xaa1-Gln-Trp-Ala-Val-Xaa2-His-Xaa3-ψ-Xaa4-NH2). RX comprises a radionuclide chelator or a trifluoroborate-containing prosthetic group. L is a linker. Xaa1 is D-Phe, Cpa (4-chlorophenylalanine), D-Cpa, Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4b]indol-3-carboxylic acid), D-Tpi, Nal (naphthylalanine), or D-Nal. Xaa2 is Gly, N-methyl-Gly or D-Ala. Xaa3 is Leu, Pro, D-Pro, or Phe. Xaa4 is Pro, Phe, Tac (thiazolidine-4-carboxylic acid), Nle (norleucine), 4-oxa-L-Pro (oxazolidine-4-carboxylic acid). The symbol ψ represents a reduced peptide bond between Xaa3 and Xaa4 in which ψ is CH2-N when Xaa4 is Pro, Tac or 4-oxa-L-Pro, or ψ is CH2N(R) when Xaa4 is Phe or Nle wherein R is H or C1-C5 linear or branched alkyl. There is also provided the use of such compounds as imaging agents or therapeutic agents.

  提供了Formula Ia（RX-L-Xaa1-Gln-Trp-Ala-Val-Xaa2-His-Xaa3-ψ-Xaa4-NH2）的波美斯因衍生物。RX包括放射性同位素螯合剂或三氟硼酸酯含基团。L是连接剂。Xaa1是D-Phe，Cpa（4-氯苯丙氨酸），D-Cpa，Tpi（2,3,4,9-四氢-1H-吡啶[3,4b]吲哚-3-羧酸），D-Tpi，Nal（萘丙氨酸）或D-Nal。Xaa2是Gly，N-甲基-Gly或D-Ala。Xaa3是Leu，Pro，D-Pro或Phe。Xaa4是Pro，Phe，Tac（噻唑啉-4-羧酸），Nle（正癸氨酸），4-氧代-L-Pro（噁唑啉-4-羧酸）。符号ψ代表Xaa3和Xaa4之间的还原肽键，其中当Xaa4为Pro，Tac或4-氧代-L-Pro时，ψ为CH2-N，或当Xaa4为Phe或Nle时，ψ为CH2N(R)，其中R为H或C1-C5线性或支链烷基。还提供了将这些化合物用作成像剂或治疗剂的用途。
• [EN] BRADYKININ RECEPTOR B1 TARGETING PROBES<br/>[FR] SONDES DE CIBLAGE DU RÉCEPTEUR B1 DE LA BRADYKININE
  申请人：BRITISH COLUMBIA CANCER AGENCY

  公开号：WO2015135082A1

  公开（公告）日：2015-09-17

  Provided in the present disclosure are peptidic imaging probes (radiotracers) useful for the non- invasive detection of cancers and other conditions or disorders characterized by expression or over- expression of the bradykinin B1 (B1R) receptor. The present peptidic probes may, for example, be 18F-AmBF3-B9858 or 18F-AmBF3-B9958. The imaging probes of the disclosure are peptidic compositions, bind with high affinity and selectivity to the B1R and are 18F- labelled and suitable for imaging procedures such as positron emission tomography (PET). These agents can be used for the early diagnosis, staging and prognosis of B1R-positive cancers or other disease conditions. The B1R imaging probes can also be used to identify B1R-positive cancer patients who may benefit from emerging B1R-targeted therapies.

  本公开提供了一种肽成像探针（放射性示踪剂），用于非侵入性检测癌症和其他表达或过表达缓激肽B1（B1R）受体的病情或疾病。本肽探针可以是18F-AmBF3-B9858或18F-AmBF3-B9958等。本公开的成像探针是肽组成物，具有高亲和力和选择性结合B1R，并且是18F标记的，适用于正电子发射断层扫描（PET）等成像程序。这些试剂可以用于B1R阳性癌症或其他疾病情况的早期诊断、分期和预后。B1R成像探针还可以用于识别可能从新兴的B1R靶向治疗中受益的B1R阳性癌症患者。
• SYNTHETIC PEPTIDE AMIDES AND DIMERS THEREOF
  申请人：Schteingart Claudio D.

  公开号：US20090264373A1

  公开（公告）日：2009-10-22

  The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P 450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.

  本发明涉及合成肽酰胺类κ-阿片受体配体，特别是表现出低P450CYP抑制和低穿透脑血屏障的κ-阿片受体激动剂。本发明的合成肽酰胺符合以下结构：含有这些化合物的制药组合物在预防和治疗与各种疾病和病况相关的疼痛和炎症方面非常有用。这种可治疗的疼痛包括内脏疼痛、神经病理性疼痛和过敏症。与炎症相关的病况，例如IBD和IBS、眼和耳炎症、其他疾病和病况，例如瘙痒、水肿、低钠血症、低钾血症、肠梗阻、咳嗽和青光眼，均可通过本发明的制药组合物进行治疗或预防。
• SYNTHETIC PEPTIDE AMIDES AND DIMERIC FORMS THEREOF
  申请人：Schteingart Claudio D.

  公开号：US20100075910A1

  公开（公告）日：2010-03-25

  The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P 450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups: The compounds are useful in the prophylaxis and treatment of pain, pruritus and inflammation associated with a variety of diseases and conditions.

  本发明涉及合成的肽酰胺，它们是kappa阿片受体的配体，特别是kappa阿片受体的激动剂，表现出低的P450CYP抑制和低的进入大脑的能力。本发明的合成肽酰胺符合以下结构：其中Xaa是D-氨基酸，G选择自以下三个组：这些化合物在预防和治疗与各种疾病和情况相关的疼痛、瘙痒和炎症方面非常有用。