1-[1-(5-methoxypyridin-2-yl)cyclohexyl]methanamine | 204067-12-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[1-(5-methoxypyridin-2-yl)cyclohexyl]methanamine
• 英文别名: 1-aminomethyl-1-(5-methoxypyridin-2-yl)cyclohexane；[1-(5-methoxy-2-pyridyl)cyclohexyl]methanamine；1-(5-Methoxy-2-pyridinyl)cyclohexanemethanamine；[1-(5-methoxypyridin-2-yl)cyclohexyl]methanamine
• CAS: 204067-12-9
• 化学式: C₁₃H₂₀N₂O
• 分子量: 220.315
• InChiKey: LUDJVLROGRFBSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[1-(5-methoxypyridin-2-yl)cyclohexyl]methanamine 在 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 52.0h， 生成 (S)-3-(1H-indol-3-yl)-N-[1-(5-methoxypyridin-2-yl)cyclohexylmethyl]-2-[(4-nitrophenyl)-carbamoylamino]propanamide
  参考文献：
  名称：

  Structure-activity relationship study towards non-peptidic positron emission tomography (PET) radiotracer for gastrin releasing peptide receptors: Development of [18F] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2-yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide

  摘要：

  Gastrin-releasing peptide receptors (GRP-Rs, also known as bombesin 2 receptors) are overexpressed in a variety of human cancers, including prostate cancer, and therefore they represent a promising target for in vivo imaging of tumors using positron emission tomography (PET). Structural modifications of the nonpeptidic GRP-R antagonist PD-176252 ((S)-1a) led to the identification of the fluorinated analog (S)-3(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy) pyridin-2-yl] cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl) ureido] propionamide ((S)-1m) that showed high affinity and antagonistic properties for GRP-R. This antagonist was stable in rat plasma and towards microsomal oxidative metabolism in vitro. (S)-1m was successfully radiolabeled with fluorine-18 through a conventional radiochemistry procedure. [F-18] (S)-1m showed high affinity and displaceable interaction for GRP-Rs in PC3 cells in vitro. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.10.031
• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 氯化亚砜 、 氨 、 水 、 氢气 、 sodium hydride 、 sodium sulfate 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 93.17h， 生成 1-[1-(5-methoxypyridin-2-yl)cyclohexyl]methanamine
  参考文献：
  名称：

  Novel 3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]propanamides as selective agonists of human formyl-peptide receptor 2

  摘要：

  N-Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) that play critical roles in inflammatory reactions, and FPR-specific interactions can possibly be used to facilitate the resolution of pathological inflammatory reactions. We here report the synthesis and biological evaluation of six pairs of chiral ureidopropanamido derivatives as potent and selective formyl peptide receptor-2 (FPR2) agonists that were designed starting from our lead agonist (S)-3-(1H-indol-3-yl)-2-[3-(4-methoxyphenyl)ureido]-N-[[1-(5-methoxy-2-pyridinyl)cyclohexyl]methyl]propanamide ((S)-9a). The new compounds were obtained in overall yields considerably higher than (S)-9a. Several of the new compounds showed agonist properties comparable to that of (S)-9a along with higher selectivity over FPR1. Molecular modeling was used to define chiral recognition by FPR2. In vitro metabolic stability of selected compounds was also assessed to obtain preliminary insight on drug-like properties of this class of compounds. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.007

文献信息

• Radiosynthesis and in vivo Evaluation of Carbon-11 (2S)-3-(1H-Indol-3-yl)-2-{[(4-methoxyphenyl)carbamoyl]amino}-N-{[1-(5-methoxypyridin-2-yl)cyclohexyl]methyl}propanamide: An Attempt to Visualize Brain Formyl Peptide Receptors in Mouse Models of Neuroinfl
  作者：Enza Lacivita、Madia Letizia Stama、Jun Maeda、Masayuki Fujinaga、Akiko Hatori、Ming-Rong Zhang、Nicola A. Colabufo、Roberto Perrone、Makoto Higuchi、Tetsuya Suhara、Marcello Leopoldo

  DOI：10.1002/cbdv.201500281

  日期：2016.7

  first attempt to visualize in vivo formyl peptide receptors (FPRs) in mouse brain by positron emission tomography (PET). FPRs are expressed in microglial cells where they mediate chemotactic activity of β-amyloid peptide in Alzheimer disease and, thus, are involved in neuroinflammatory processes. To this purpose, we have selected (2S)-3-(1H-Indol-3-yl)-2-[(4-methoxyphenyl)carbamoyl]amino}-N-[1-(5-m

  在这里，我们描述了通过正电子发射断层扫描（PET）可视化小鼠大脑中的体内甲酰基肽受体（FPRs）的首次尝试。FPR在小胶质细胞中表达，它们在阿尔茨海默病中介导β淀粉样肽的趋化活性，因此参与神经炎性过程。为此，我们选择了（2S）-3-（1H-吲哚-3-基）-2-[（（4-甲氧基苯基）氨基甲酰基]氨基} -N-[1-（5-甲氧基吡啶-2-酰基）环己基]甲基}丙酰胺（（S）-1），我们之前已将其鉴定为有效的非肽FPR激动剂。（S）-[（（11）C] -1）以高放射化学产率制备。（S）-[（（11）C] -1）的血脑屏障渗透性非常低，因此无法积聚到大脑中。此外，（S）-[（（11）C] -1）无法标记PS19和APP23小鼠脑切片中的FPRs受体，阿尔茨海默氏病的两种动物模型。尽管（S）-[（11）C] -1不适合可视化大脑中的FPR，但这项研究为设计和表征未来潜在的PET放射性配体（通过PET可视化大脑FPR）提供了有用的信息。
• Treatment of sexual dysfunction
  申请人：——

  公开号：US20020169101A1

  公开（公告）日：2002-11-14

  Bombesin receptor antagonists have been found to be useful in the treatment of sexual dysfunction in both males and females. They may be selective BB1 antagonists or mixed BB1/BB2 antagonists. Combinations are disclosed of bombesin receptor antagonists with a range of other active compounds, for example PDE5 inhibitors, NEP inhibitors and lasofoxifene.

  Bombesin受体拮抗剂已被发现在男性和女性的性功能障碍治疗中非常有用。它们可以是选择性BB1拮抗剂或混合BB1 / BB2拮抗剂。揭示了与一系列其他活性化合物的Bombesin受体拮抗剂的组合，例如PDE5抑制剂，NEP抑制剂和lasofoxifene。
• Bombesin receptor antagonists
  申请人：——

  公开号：US20040110768A1

  公开（公告）日：2004-06-10

  Bombesin receptor antagonists are provided which are compounds of formula (I) or pharmaceutically acceptable salts thereof: 1 wherein j, k, l, m, n, q, r, Ar, Ar 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and X are as defined in the description. The compounds of the invention have an affinity for the BB 1 receptor and some of them also have affinity for the BB 2 receptor. Accordingly they may be useful for the diagnosis, prevention, or treatment of male and female sexual dysfunction. They can also be used in the diagnosis, prevention or treatment of anxiety and panic disorders, social phobia, depression, psychoses, sleeping disorders, memory impairment, pulmonary hypertension, lung repair and lung development disorders, cancer including prostate cancer and pancreatic cancer, hepatic porphyria, gastrointestinal secretory disturbances, gastrointestinal disorders including colitis, Crohn's disease and inflammatory bowel disease, emesis, anorexia, pain, seasonal affective disorders, feeding disorders or pruritus.

  提供了化合物(I)或其药学上可接受的盐，其是Bombesin受体拮抗剂：1其中j、k、l、m、n、q、r、Ar、Ar1、R1、R2、R3、R4、R5、R6和X如说明书中所定义的。本发明的化合物具有对BB1受体的亲和力，其中一些化合物还具有对BB2受体的亲和力。因此，它们可能对男性和女性的性功能障碍的诊断、预防或治疗有用。它们还可用于焦虑和恐慌障碍、社交恐惧症、抑郁症、精神病、睡眠障碍、记忆障碍、肺动脉高压、肺修复和肺发育障碍、包括前列腺癌和胰腺癌在内的癌症、肝卟啉症、胃肠分泌紊乱、包括结肠炎、克罗恩病和炎症性肠病在内的胃肠疾病、呕吐、厌食、疼痛、季节性情感障碍、进食障碍或瘙痒的诊断、预防或治疗中使用。
• Bombesin antagonists
  申请人：Pfizer Inc.

  公开号：US20040063643A1

  公开（公告）日：2004-04-01

  Compounds of formula (I): 1 and their salts, solvates, prodrugs, etc., wherein the substituents have the values mentioned herein, are bombesin antagonists, which have utility in a variety of therapeutic areas including male and female sexual dysfunction, particularly female sexual dysfunction (FSD) especially wherein the FSD is female sexual arousal disorder (FSAD) and male erectile dysfunction (MED)

  式(I)的化合物及其盐、溶剂合物、前药等，其中取代基的取值如下所述，是炸弹素拮抗剂，在包括男性和女性性功能障碍等多种治疗领域中具有功效，尤其是在女性性功能障碍（FSD）中，特别是在女性性欲障碍（FSAD）和男性勃起功能障碍（MED）中。
• TREATMENT OF SEXUAL DYSFUNCTION WITH BOMBESIN RECEPTOR ANTAGONISTS
  申请人：Warner-Lambert Company LLC

  公开号：EP1333824B1

  公开（公告）日：2005-09-07