N-环己基-N-[2-(3,5-二甲基吡唑-1-基)-6-甲基嘧啶-4-基]胺 | 73029-73-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: N-环己基-N-[2-(3,5-二甲基吡唑-1-基)-6-甲基嘧啶-4-基]胺
• 中文别名: N-环己基-N-[2-(3,5-二甲基-吡唑-1-基)-6-甲基-4-嘧啶胺；N-环己基-n-[2-(3,5-二甲基-吡唑-1-基)-6-甲基-4-嘧啶胺
• 英文名称: CyPPA
• 英文别名: cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine；N-cyclohexyl-2-(3,5-dimethylpyrazol-1-yl)-6-methylpyrimidin-4-amine
• CAS: 73029-73-9
• 化学式: C₁₆H₂₃N₅
• 分子量: 285.392
• InChiKey: USEMRPYUFJNFQN-UHFFFAOYSA-N

物化性质

• 沸点：
  512.2±42.0 °C(Predicted)
• 密度：
  1.23
• 溶解度：
  二甲基亚砜：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36/37
• 危险标志：
  GHS07
• 危险类别码：
  R36/37/38
• 危险性描述：
  H315,H319,H335,H413
• 危险性防范说明：
  P261,P305 + P351 + P338
• 海关编码：
  2933990090

制备方法与用途

生物活性

CyPPA 是 hSK3 和 hSK2 的阳性调节剂，其 EC50 值分别为 14 μM 和 5.6 μM。CyPPA 对 hSK1 和 hIK 通道无活性。

体外研究

CyPPA 能浓度依赖性地增加通道激活的显性钙 (Ca²⁺) 敏感性，将 Ca²⁺ 的 EC₅₀ 值从 429 nM 变为 59 nM。

体内研究

作为一种小导管钙 (Ca²⁺)-激活钾 (K⁺) 通道的阳性调节剂，CyPPA 能抑制子宫的阵发性收缩，并推迟早产鼠的预产期。

反应信息

• 作为产物：
  描述：

  3,5-二甲基吡唑 、 2-chloro-4-cyclohexylamino-6-methylpyrimidine 以 乙腈 为溶剂， 反应 0.5h， 以38%的产率得到N-环己基-N-[2-(3,5-二甲基吡唑-1-基)-6-甲基嘧啶-4-基]胺
  参考文献：
  名称：

  Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca²⁺-activated K⁺channels

  摘要：

  Background and purpose:Positive modulators of small conductance Ca2+‐activated K+ channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non‐excitable cells. The prototype compound 1‐EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca2+‐activated K+ channel (IK). This paper demonstrates, for the first time, subtype‐selective positive modulation of SK channels.Experimental approach:Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐pyrimidin‐4‐yl]‐amine (CyPPA) on recombinant hSK1‐3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells.Key results:CyPPA was found to be a positive modulator of hSK3 (EC50 = 5.6 ± 1.6 μM, efficacy 90 ± 1.8 %) and hSK2 (EC50 = 14 ± 4 μM, efficacy 71 ± 1.8 %) when measured in inside‐out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration‐dependent increase in the apparent Ca2+‐sensitivity of channel activation, changing the EC50(Ca2+) from 429 nM to 59 nM.Conclusions and implications:As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1‐EBIO and NS309 to distinguish SK3/SK2‐ from SK1/IK‐mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co‐express in certain peripheral tissues.British Journal of Pharmacology (2007) 151, 655–665; doi:10.1038/sj.bjp.0707281

  DOI：

  10.1038/sj.bjp.0707281

文献信息

• Pyrazolyl-Pyrimidines as Potassium Channel Modulating Agents and Their Medical Use
  申请人：Eriksen Birgitte L.

  公开号：US20090036475A1

  公开（公告）日：2009-02-05

  This invention relates to novel potassium channel modulating agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular respiratory diseases, epilepsy, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic heart disease, angina pectoris, coronary heart disease, traumatic brain injury, psychosis, schizophrenia, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labour, baldness, cancer, immune suppression or pain.

  这项发明涉及新型钾通道调节剂，以及它们在制备药物组合物中的应用。此外，该发明针对用于治疗或缓解与钾通道活性相关的疾病或障碍的药物组合物，特别是呼吸道疾病、癫痫、抽搐、血管痉挛、冠状动脉痉挛、肾功能紊乱、多囊肾病、膀胱痉挛、尿失禁、膀胱排出道梗阻、肠易激综合征、胃肠功能紊乱、分泌性腹泻、缺血、脑缺血、缺血性心脏病、心绞痛、冠心病、创伤性脑损伤、精神病、精神分裂症、焦虑、抑郁症、痴呆、记忆和注意力缺陷、阿尔茨海默病、痛经、嗜睡症、雷诺氏病、间歇性跛行、干燥综合征、偏头痛、心律失常、高血压、缺席性癫痫发作、肌肉肌无力症、干燥综合症、2型糖尿病、胰岛素高血症、早产、秃头、癌症、免疫抑制或疼痛。
• Potassium channel modulators
  申请人：Cadent Therapeutics, Inc.

  公开号：US10351553B2

  公开（公告）日：2019-07-16

  Provided herein are compounds of the formula: or pharmaceutically acceptable salts thereof, and compositions comprising such compounds for use in the treatment of diseases or conditions responsive to modulation of the small conductance calcium-activated potassium channel (SK channel).

  本文提供的是式中化合物： 或其药学上可接受的盐，以及包含此类化合物的组合物，用于治疗对调节小电导钙激活钾通道（SK 通道）有反应的疾病或病症。
• Treatment of learning disabilities and other neurological disorders with SK channel inhibitor(s)
  申请人：Children's National Medical Center

  公开号：US10555989B2

  公开（公告）日：2020-02-11

  Methods for treating learning disabilities associated with fetal alcohol syndrome and other neurological disorders by administering SK channel blockers, antagonists, inhibitors or modifiers like tamapin.

  通过施用 SK 通道阻滞剂、拮抗剂、抑制剂或他马平等调节剂来治疗与胎儿酒精综合征和其他神经系统疾病相关的学习障碍的方法。
• Method of increasing satellite cell proliferation with an HDAC inhibitor
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：US10660902B2

  公开（公告）日：2020-05-26

  The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.

  本发明提供了诱导、增强或增加卫星细胞增殖的方法，以及用于筛选诱导、增强或增加卫星细胞增殖的候选化合物的检测方法。本发明还提供了修复或再生受试者受损肌肉组织的方法。
• Small molecules for mouse satellite cell proliferation
  申请人：President and Fellows of Harvard College

  公开号：US11026952B2

  公开（公告）日：2021-06-08

  The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.

  本发明提供了诱导、增强或增加卫星细胞增殖的方法，以及用于筛选诱导、增强或增加卫星细胞增殖的候选化合物的检测方法。本发明还提供了修复或再生受试者受损肌肉组织的方法。