octahydro-pyrrolo[3,2-b]pyrrole | 5839-99-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: octahydro-pyrrolo[3,2-b]pyrrole
• 英文别名: Octahydropyrrolo[3,2-b]pyrrole；1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,2-b]pyrrole
• CAS: 5839-99-6
• 化学式: C₆H₁₂N₂
• mdl: MFCD17977180
• 分子量: 112.175
• InChiKey: GLUABPSZMHYCNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  octahydro-pyrrolo[3,2-b]pyrrole 、 (2R)-1-([(2S)-1-(3,3,3-triphenylpropanoyl)pyrrolidin-2-yl]carbonyl)pyrrolidine-2-carboxylic acid 在 2-chlorotrityl chloride resin 、 N,N-二异丙基乙胺 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.67h， 生成 1-[(2S)-2-[(2R)-2-(2,3,3a,5,6,6a-hexahydro-1H-pyrrolo[3,2-b]pyrrole-4-carbonyl)pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-3,3,3-triphenylpropan-1-one
  参考文献：
  名称：

  Identification of a Novel 4-Aminomethylpiperidine Class of M₃ Muscarinic Receptor Antagonists and Structural Insight into Their M₃ Selectivity

  摘要：

  Identification of a novel class of potent and highly selective M-3 muscarinic antagonists is described. First, the structure-activity relationship in the cationic amine core of our previously reported triphenylpropionamide class of M-3 selective antagonists was explored by a small diamine library constructed in solid phase. This led to the identification of M-3 antagonists with a novel piperidine pharmacophore and significantly improved subtype selectivity from a previously reported class. Successive modification on the terminal triphenylpropionamide part of the newly identified class gave 14a as a potent M-3 selective antagonist that had > 100-fold selectivity versus the M-1, M-2, M-4, and M-5 receptors (M-3: K-i = 0.30 nM, M-1/M-3 = 570-fold, M-2/M-3 = 1600-fold, M-4/M-3 = 140-fold, M-5/M-3 = 12000-fold). The possible rationale for its extraordinarily higher subtype selectivity than reported M-3 antagonists was hypothesized by sequence alignment of multiple muscarinic receptors and a computational docking of 14a into transmembrane domains of M-3 receptors.

  DOI：

  10.1021/jm051205r

文献信息

• Npy antagonists, preparation and uses
  申请人：Botez Iuliana

  公开号：US20090233910A1

  公开（公告）日：2009-09-17

  The present invention concerns novel compounds, their preparation and their uses, therapeutic uses in particular. More specifically it concerns derivative compounds having at least two aromatic cycles, their preparation and their uses, in particular in the area of human or animal health. These compounds have an affinity for the biological receptors of neuropeptide Y, NPY, present in the central and peripheral nervous systems. The compounds of the invention are preferably NPY antagonists, and more particularly antagonists of sub-type NPY Y1, and can therefore be used for the therapeutic or prophylactic treatment of any disorder involving NPY. The present invention also concerns pharmaceutical compositions containing said compounds, their preparation and their uses, as well as treatment methods using said compounds.

  本发明涉及新颖化合物，它们的制备和用途，特别是在治疗方面的用途。更具体地说，它涉及至少具有两个芳香环的衍生化合物，它们的制备和用途，特别是在人类或动物健康领域。这些化合物对存在于中枢和外周神经系统中的神经肽Y（NPY）的生物受体具有亲和力。本发明的化合物优选为NPY拮抗剂，更具体地说是NPY Y1亚型的拮抗剂，因此可用于治疗或预防涉及NPY的任何疾病。本发明还涉及含有所述化合物的药物组合物，其制备和用途，以及使用所述化合物的治疗方法。
• INDOLE CARBOXAMIDE COMPOUNDS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160115126A1

  公开（公告）日：2016-04-28

  Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR 4 or N; R 1 , R 2 , R 3 , R 4 , and A are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  揭示了Formula (I)的化合物： 或其盐，其中：X为CR 4 或N；R 1 ，R 2 ，R 3 ，R 4 和A在此处定义。还揭示了使用这些化合物作为Bruton's酪氨酸激酶（Btk）抑制剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓各种治疗领域的疾病或疾病的进展方面非常有用，如自身免疫疾病和血管疾病。
• [EN] NUCLEIC ACID CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS DE TYPE ACIDE NUCLÉIQUE ET LEURS UTILISATIONS
  申请人：TRANSLATE BIO MA INC

  公开号：WO2018013525A1

  公开（公告）日：2018-01-18

  Provided herein are conjugates comprising targeting moieties such as sugars, folates and cell-penetrating peptides, which can be used for the improved delivery of agents (e.g., nucleic acids, such as oligonucleotides or mRNAs, or other agents) to cells. The invention provides conjugates and compounds comprising targeting moieties, methods for preparing the same, and intermediates useful in their preparation. In another aspect, the present invention provides formulations (e.g., pharmaceutical compositions) comprising the targetting moiety-containing conjugates and compounds. The present invention also provides methods for delivering agents (e.g., nucleic acids such as oligonucleotides or mRNAs) to a cell, methods for treating and/or preventing a disease or condition in a subject, and methods for modulating gene expression in a cell or a subject. Further, provided herein are kits comprising the conjugates, or formulations thereof; and kits for the preparation of conjugates described herein.

  本文提供了包含靶向基团的共轭物，如糖类、叶酸和穿膜肽，可用于改善药物（例如核酸，如寡核苷酸或mRNA，或其他药物）对细胞的传递。该发明提供了包含靶向基团的共轭物和化合物，以及其制备方法和制备过程中有用的中间体。另一方面，本发明提供了包含靶向基团的共轭物和化合物的配方（例如，药物组合物）。本发明还提供了将药物（例如核酸，如寡核苷酸或mRNA）传递至细胞的方法，用于治疗和/或预防受试者疾病或状况的方法，以及用于调节细胞或受试者基因表达的方法。此外，本文提供了包含这些共轭物或其配方的试剂盒；以及用于制备本文所述共轭物的试剂盒。
• [EN] HDAC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA HDAC ET SES UTILISATIONS
  申请人：ENVIVO PHARMACEUTICALS INC

  公开号：WO2009137503A1

  公开（公告）日：2009-11-12

  Inhibitors of histone deacetylase, including compounds having a diazabicyclo[2.2.1]heptan-2-yl moiety are described together with methods for treating various disorders with such compounds.

  抑制组蛋白去乙酰化酶的抑制剂，包括具有二氮杂双环[2.2.1]庚烷-2-基基团的化合物，以及使用这些化合物治疗各种疾病的方法被描述。
• CELL-PERMEABLE IMAGING SENSORS AND USES THEREOF
  申请人：Massachusetts Institute of Technology

  公开号：US20190184036A1

  公开（公告）日：2019-06-20

  The disclosure relates in some aspects to imaging agents, and in particular, imaging agents for sensing of calcium signaling. According to some embodiments of the disclosure, contrast agents for magnetic resonance imaging and related technologies are provided, and methods of making and using the contrast agents.

  本公开涉及某些方面的成像剂，特别是用于检测钙信号传递的成像剂。根据本公开的一些实施例，提供了用于磁共振成像和相关技术的对比剂，以及制造和使用这些对比剂的方法。