(3,5-bis-trifluoromethyl-benzyl)-cyclopropyl-amine | 290297-42-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3,5-bis-trifluoromethyl-benzyl)-cyclopropyl-amine
• 英文别名: (3,5-Bistrifluoromethylbenzyl)cyclopropylamine；N-[[3,5-bis(trifluoromethyl)phenyl]methyl]cyclopropanamine
• CAS: 290297-42-6
• 化学式: C₁₂H₁₁F₆N
• 分子量: 283.216
• InChiKey: SSAYYJNJMHQQIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3,5-bis-trifluoromethyl-benzyl)-cyclopropyl-amine 、 Boc-2′,6′-dimethyltyrosine-D-Arg(Pbf)-(4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one)-β-Ala-OH 在 水 、 1-羟基苯并三唑 、 三氟乙酸 、 N,N'-二异丙基碳二亚胺 作用下， 反应 3.0h， 生成 RCCHM1
  参考文献：
  名称：

  Analgesic Properties of Opioid/NK1 Multitarget Ligands with Distinct in Vitro Profiles in Naive and Chronic Constriction Injury Mice

  摘要：

  The lower efficacy of opioids in neuropathic pain may be due to the increased activity of pronociceptive systems such as substance P. We present evidence to support this hypothesis in this work from the spinal cord in a neuropathic pain model in mice. Biochemical analysis confirmed the elevated mRNA and protein level of pronociceptive substance P, the major endogenous ligand of the neurokinin-1 (NK1) receptor, in the lumbar spinal cord of chronic constriction injury (CCI)-mice. To improve opioid efficacy in neuropathic pain, novel compounds containing opioid agonist and neurokinin 1 (NK1) receptor antagonist pharmacophores were designed. Structure-activity studies were performed on opioid agonist/NK1 receptor antagonist hybrid peptides by modification of the C-terminal amide substituents. All compounds were evaluated for their affinity and in vitro activity at the mu opioid (MOP) and delta opioid (DOP) receptors, and for their affinity and antagonist activity at the NK1 receptor. On the basis of their in vitro profiles, the analgesic properties of two new bifunctional hybrids were evaluated in naive and CCI-mice, representing models for acute and neuropathic pain, respectively. The compounds were administered to the spinal cord by lumbar puncture. In naive mice, the single pharmacophore opioid parent compounds provided better analgesic results, as compared to the hybrids (max 70% MPE), raising the acute pain threshold close to 100% MPE. On the other hand, the opioid parents gave poor analgesic effects under neuropathic pain conditions, while the best hybrid delivered robust (close to 100% MPE) and long lasting alleviation of both tactile and thermal hypersensitivity. The results presented emphasize the potential of opioid/NK1 hybrids in view of analgesia under nerve injury conditions.

  DOI：

  10.1021/acschemneuro.7b00226
• 作为产物：
  描述：

  3,5-双三氟甲基苯甲醛 、 环丙胺 生成 (3,5-bis-trifluoromethyl-benzyl)-cyclopropyl-amine
  参考文献：
  名称：

  Novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives

  摘要：

  本发明涉及新型的3,4-二取代的1,2,3,6-四氢吡啶衍生物和相关化合物，以及它们作为药物制剂中活性成分的使用。本发明还涉及相关方面，包括制备该化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为肾素抑制剂的使用。

  公开号：

  US20060235056A1

文献信息

• [EN] NOVEL 3,4-DISUBSTITUTED 1,2,3,6-TETRAHYDROPYRIDINE DERIVATIVES<br/>[FR] NOUVEAUX DERIVES DE LA 1,2,3,6-TETRAHYDROPYRIDINE 3,4-DISUBSTITUEE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2004096769A1

  公开（公告）日：2004-11-11

  The invention relates to novel 3,4-disubstituted 1,2,3,6-tetrahydropyridine derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  本发明涉及新型的3,4-二取代-1,2,3,6-四氢吡啶衍生物及相关化合物，以及它们作为活性成分用于制备药物组合物的用途。本发明还涉及相关方面，包括制备这些化合物的方法、含有一种或多种这些化合物的药物组合物，尤其是它们作为肾素抑制剂的用途。
• 4-phenyl-pyridine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06297375B1

  公开（公告）日：2001-10-02

  The compounds of the related invention are related to 4-phenyl-pyridine derivatives connected by a bridge containing oxygen or nitrogen to a phenyl derivative.

  相关发明的化合物是指通过含氧或氮的桥连接到苯衍生物的4-苯基吡啶衍生物。
• 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1035115A1

  公开（公告）日：2000-09-13

  The present invention relates to compounds of the general formula wherein Ris hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl; R1is hydrogen or halogen; or R and R1may be together -CH=CH-CH=CH-; R2 and R2'are independently from each other hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano; or R2 and R2'may be together -CH=CH-CH=CH-, optionally substituted by one or two substituents selected from lower alkyl or lower alkoxy; R3is hydrogen, lower alkyl or form a cycloalkyl group; R4is hydrogen, -N(R5)2, -N(R5)(CH2)nOH, -N(R5)S(O)2-lower alkyl, -N(R5)S(O)2-phenyl, -N=CH-N(R5)2, -N(R5)C(O)R5 or a cyclic tertiary amine of the group R5is, independently from each other, hydrogen, C3-6-cycloalkyl, benzyl or lower alkyl; R6is hydrogen, hydroxy, lower alkyl, -(CH2)nCOO-lower alkyl, -N(R5)CO-lower alkyl, hydroxy-lower alkyl, cyano, -(CH2)nO(CH2)nOH, -CHO or a 5-or 6 membered heterocyclic group, optionally bonded via an alkylene group, Xis -C(O)N(R5)-, -(CH2)mO-, -(CH2)mN(R5)-, -N(R5)C(O)-, or -N(R5)(CH2)m-; nis 0-4; and mis 1 or 2; and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I show a high affinity to the NK- 1 receptor. They may be used for the treatment of diseases, which relate to NK- 1 receptor antagonists.

  本发明涉及通式如下的化合物 式中 Ris氢、低级烷基、低级烷氧基、卤素或三氟甲基； R1 是氢或卤素；或 R和R1可以是-CH=CH-CH=CH-； R2 和 R2'彼此独立地为氢、卤素、三氟甲基、低级烷氧基或氰基；或 R2 和 R2'可以同时为-CH=CH-CH=CH-，任选被一个或两个选自低级烷基或低级烷氧基的取代基取代； R3 是氢、低级烷基或形成环烷基； R4 是氢、-N(R5)2、-N(R5)(CH2)nOH、-N(R5)S(O)2-低级烷基、-N(R5)S(O)2-苯基、-N=CH-N(R5)2、-N(R5)C(O)R5 或以下基团的环状叔胺 R5 相互独立地为氢、C3-6-环烷基、苄基或低级烷基； R6 是氢、羟基、低级烷基、-( )nCOO-低级烷基、-N(R5)CO-低级烷基、羟基-低级烷基、氰基、-( )nO( )nOH、-CHO 或可选择通过亚烷基键合的 5 或 6 位杂环基团、 X是-C(O)N(R5)-、-( )mO-、-( )mN(R5)-、-N(R5)C(O)-或-N(R5)( )m-； n 为 0-4；以及 误差为 1 或 2； 及其药学上可接受的酸加成盐。式 I 的化合物对 NK- 1 受体具有很高的亲和力。它们可用于治疗与 NK- 1 受体拮抗剂有关的疾病。
• NOVEL 3,4-DISUBSTITUTED 1,2,3,6-TETRAHYDROPYRIDINE DERIVATIVES
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1620403A1

  公开（公告）日：2006-02-01
• US6297375B1
  申请人：——

  公开号：US6297375B1

  公开（公告）日：2001-10-02