1-(3-chloropyridin-2-yl)methanamine dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(3-chloropyridin-2-yl)methanamine dihydrochloride
• 英文别名: (3-chloropyridin-2-yl)methanamine dihydrochloride；(3-Chloropyridin-2-yl)methanamine hydrochloride；(3-chloropyridin-2-yl)methanamine;hydrochloride
• 化学式: C₆H₇ClN₂*2ClH
• 分子量: 215.51
• InChiKey: DEPQAELCACZEMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  38.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-chloropyridin-2-yl)methanamine dihydrochloride 在 盐酸 、 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 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 205.0h， 生成 1-(2-{[2-(1H-1,3-benzodiazol-2-yl)ethyl]amino}ethyl)-N-[(3-chloropyridin-2-yl)methyl]-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  [EN] FERROPORTIN INHIBITORS
  [FR] NOUVEAUX INHIBITEURS DE LA FERROPORTINE

  摘要：

  公开号：

  WO2017068089A9
• 作为产物：
  描述：

  2,3-二氯吡啶 在 镍 ammonium hydroxide 、 四(三苯基膦)钯 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 95.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 1-(3-chloropyridin-2-yl)methanamine dihydrochloride
  参考文献：
  名称：

  Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors. Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines

  摘要：

  Recent efforts in the field of thrombin inhibitor research have focused on the identification of compounds with good oral bioavailability and pharmacokinetics. In this manuscript we describe a metabolism-based approach to the optimization of the 3-(2-phenethylamino)-6-methylpyrazinone acetamide template (e.g., 1) which resulted in the,modification of each of the three principal components (i.e., P1, P2, P3) comprising this series. As a result of these studies, several potent thrombin inhibitors (e.g., 20, 24, 25) were identified which exhibit high levels of oral bioavailability and long plasma half-lives.

  DOI：

  10.1021/jm020311f

文献信息

• Discovery and Characterization of BAY 1214784, an Orally Available Spiroindoline Derivative Acting as a Potent and Selective Antagonist of the Human Gonadotropin-Releasing Hormone Receptor as Proven in a First-In-Human Study in Postmenopausal Women
  作者：Olaf Panknin、Andrea Wagenfeld、Wilhelm Bone、Eckhard Bender、Katrin Nowak-Reppel、Amaury E. Fernández-Montalván、Reinhard Nubbemeyer、Stefan Bäurle、Sven Ring、Norbert Schmees、Olaf Prien、Martina Schäfer、Christian Friedrich、Thomas M. Zollner、Andreas Steinmeyer、Thomas Mueller、Gernot Langer

  DOI：10.1021/acs.jmedchem.0c01076

  日期：2020.10.22

  overcome such issues, we aimed to identify novel, small-molecule hGnRH-R antagonists. This led to the discovery of compound BAY 1214784, an orally available, potent, and selective hGnRH-R antagonist. Altering the geminal dimethylindoline core of the initial hit compound to a spiroindoline system significantly improved GnRH-R antagonist potencies across several species, mandatory for a successful compound

  子宫肌瘤的生长是性激素依赖性的，并且通常与高度致残的症状有关。大多数治疗选择包括控制这些激素的作用，最终阻断增殖性雌激素信号传导（即，人类促性腺激素释放激素受体[hGnRH-R]活性的口服避孕药/拮抗剂）。然而，完全的hGnRH-R阻断会导致更年期症状并影响骨矿化，从而限制了治疗时间或要求使用雌激素补充疗法。为了克服这些问题，我们旨在鉴定新颖的小分子hGnRH-R拮抗剂。这导致了化合物BAY 1214784的发现，该化合物为口服有效，有效的选择性hGnRH-R拮抗剂。将最初命中化合物的双甲基二氢吲哚啉核心改变为螺二氢吲哚系统，可显着提高跨多个物种的GnRH-R拮抗剂效价，这是成功实现体内化合物优化的必要条件。在一项针对绝经后妇女的首次人体研究中，每天使用BAY 1214784进行的治疗有效地降低了血浆黄体生成素的水平，最高可降低49％，同时还具有较低的药代动力学变异性和良好的耐受性。
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009083526A1

  公开（公告）日：2009-07-09

  The invention relates to novel benzimidazole compounds of formula (I) wherein R1 to R1 are as defined in the specification, pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing them and their use in medicine. In particular, the invention relates to compounds that are agonists of peroxisome proliferators-activated receptorγ (PPARγ).

  这项发明涉及公式（I）中R1到R1所定义的新型苯并咪唑化合物，其药学上可接受的盐，含有它们的药物组合物以及它们在医学上的用途。具体而言，该发明涉及激动过氧化物酶体增殖物激活受体γ（PPARγ）的激动剂化合物。
• [EN] THERAPEUTIC HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES THÉRAPEUTIQUES
  申请人：GILEAD SCIENCES INC

  公开号：WO2019040102A1

  公开（公告）日：2019-02-28

  Compounds having the following Formula (I) and/or Formula (II) and methods of their use and preparation are disclosed.

  揭示了具有以下化学式（I）和/或化学式（II）的化合物，以及它们的使用和制备方法。
• Spiroindoline carbocycle derivatives and pharmaceutical compositions thereof
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP2881391A1

  公开（公告）日：2015-06-10

  Spiroindoline carbocycle derivatives, process for their preparation and pharmaceutical compositions thereof, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially sex-hormone-related diseases in both men and women, in particularly those selcted from the group of endometriosis, uterine fibroids, polycystic ovarian disease, hirsutism, precocious puberty, gonadal steroid-dependent neoplasia such as cancers of the prostate, breast and ovary, gonadotrope pituitary adenomas, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hypertrophy, contraception and infertility (e.g., assisted reproductive therapy such as in vitro fertilization). The present application relates in particular to spiroindoline derivatives as gonadotropin-releasing hormone (GnRH) receptor antagonists.

  螺环吲哚烷衍生物，其制备方法和药物组合物，用于治疗和/或预防疾病，以及用于制造治疗和/或预防疾病的药物，特别是男性和女性的性激素相关疾病，尤其是选择自子宫内膜异位症、子宫肌瘤、多囊卵巢综合征、多毛症、性早熟、依赖性性腺类固醇的肿瘤，如前列腺、乳腺和卵巢癌、性腺激素促性腺垂体瘤、睡眠呼吸暂停、肠易激综合征、经前综合征、良性前列腺增生、避孕和不孕不育（例如辅助生殖疗法，如体外受精）。本申请特别涉及螺环吲哚衍生物作为促性腺释放激素（GnRH）受体拮抗剂。
• [EN] FERROPORTIN INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE LA FERROPORTINE
  申请人：VIFOR (INTERNATIONAL) AG

  公开号：WO2017068089A9

  公开（公告）日：2017-09-14