methyl 4'-(aminomethyl)-3,3'-difluoro-1,1'-biphenyl-2-carboxylate | 887278-70-8

• 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: methyl 4'-(aminomethyl)-3,3'-difluoro-1,1'-biphenyl-2-carboxylate
• 英文别名: methyl 4'-(aminomethyl)-3,3'-difluorobiphenyl-2-carboxylate；methyl 2-[4-(aminomethyl)-3-fluorophenyl]-6-fluorobenzoate
• CAS: 887278-70-8
• 化学式: C₁₅H₁₃F₂NO₂
• 分子量: 277.271
• InChiKey: STTXIKBQTIONKA-UHFFFAOYSA-N

物化性质

• 沸点：
  414.0±45.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4'-(aminomethyl)-3,3'-difluoro-1,1'-biphenyl-2-carboxylate 在 sodium hydroxide 、 TEA 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 6-({[3,3'-difluoro-2'-(methoxycarbonyl)biphenyl-4-yl]methyl}amino)nicotinic acid
  参考文献：
  名称：

  5-Piperazinyl pyridine carboxamide bradykinin B1 antagonists

  摘要：

  A series of 2,3-diaminopyridine bradykinin B-1 antagonists was modified to mitigate the potential for bioactivation. Removal of the 3-amino group and incorporation of basic 5-piperazinyl carboxamides at the pyridine 5-position provided compounds with high affinity for the human B-1 receptor. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.112
• 作为产物：
  描述：

  2-氟-6-碘苯甲酸 在 镍 氨 、 氢气 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， 反应 7.5h， 生成 methyl 4'-(aminomethyl)-3,3'-difluoro-1,1'-biphenyl-2-carboxylate
  参考文献：
  名称：

  Development of Orally Bioavailable and CNS Penetrant Biphenylaminocyclopropane Carboxamide Bradykinin B₁ Receptor Antagonists

  摘要：

  A series of biphenylaminocyclopropane carboxamide based bradykinin B-1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B-1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.

  DOI：

  10.1021/jm061094b

文献信息

• Substituted biaryl-carboxylate derivatives
  申请人：Wood R. Michael

  公开号：US20060111392A1

  公开（公告）日：2006-05-25

  Substituted biaryl-carboyxlate derivatives are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  替代联苯基羧酸酯衍生物是布雷金肽B1拮抗剂或逆向激动剂，在治疗或预防与布雷金肽B1途径相关的疼痛和炎症症状方面非常有用。
• 2-(Bicyclo)alkylamino-derivatives as mediators of chronic pain and inflammation
  申请人：Bock G. Mark

  公开号：US20060106011A1

  公开（公告）日：2006-05-18

  Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  本文所披露的化合物是bradykinin B1拮抗剂化合物，可用于治疗或预防与bradykinin B1通路相关的疼痛和炎症等症状。
• Novel small molecule bradykinin B1 receptor antagonists. Part 2: 5-membered diaminoheterocycles
  作者：Gunther Zischinsky、Roland Stragies、Marco Schaudt、Jochen R. Pfeifer、Christoph Gibson、Elsa Locardi、Dirk Scharn、Uwe Richter、Holger Kalkhof、Klaus Dinkel、Karsten Schnatbaum

  DOI：10.1016/j.bmcl.2009.11.120

  日期：2010.2

  Efforts to find new bradykinin B-1 receptor antagonists identified 2-aminobenzimidazole as a novel core. Subsequent transformation into five-membered diaminoheterocycle derivatives and their synthesis and SAR is described. This resulted in compounds with low nanomolar activity. (C) 2009 Elsevier Ltd. All rights reserved.
• SMALL MOLECULE BRADYKININ B1 RECEPTOR ANTAGONISTS
  申请人：Jerini AG

  公开号：EP2396301A2

  公开（公告）日：2011-12-21
• [EN] SMALL MOLECULE BRADYKININ B1 RECEPTOR ANTAGONISTS<br/>[FR] PETITES MOLÉCULES ANTAGONISTES DU RÉCEPTEUR B1 DE LA BRADYKININE
  申请人：JERINI AG

  公开号：WO2010091876A2

  公开（公告）日：2010-08-19

  The present invention is related to a compound of the formula (I): or a pharmacologically acceptable salt, solvate or hydrate thereof, wherein A is formula (II) (III) (IV), X is Ch or N; R1, R2, R3, R4, R6, R7, and R8 are each and independently of each other selected from hydrogen atom, halogen atom, hydroxy, cyano, amino, alkyl, or optionally substituted heteroalkyl; R5 is a halogen atom, hydroxy, cyano, amino, an alkyl, an optionally substituted heteroalkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted alkylcycloalkyl, an optionally substituted heteroalkylcycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteroaralkyl; R9 is a hydrogen atom, an alkyl, or a heteroalkyl; R10 is a hydrogen atom, an alkyl, an optionally substituted heteroalkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted aralkyl, or an optionally substituted heteroaralkyl; R11 is an alkyl, an optionally substituted heteroalkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted alkylcycloalkyl, an optionally substituted heteroalkylcycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteroaralkyl; R12 is a hydrogen atom, an alkyl, an optionally substituted heteroalkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted aryl, an optionally substituted aralkyl, or an optionally substituted heteroaralkyl; B is O or N; Z1 and Z2 are each and independently of each other selected from C or N, and Z3 and Z4 are each and independently of each other selected from C, S, O or N; R13 is an alkyl, an optionally substituted heteroalkyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted alkylcycloalkyl, an optionally substituted heteroalkylcycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aralkyl, or an optionally substituted heteroaralkyl; R14 and R15, if present, are (i) each and independently of each other selected from hydrogen atom, halogen atom, CN, hydroxy, =O, alkyl, C3-C6-cycloalkyl, heteroalkyl or alkoxy; or (ii) joined together to form a carbocyclic or heterocyclic 5- or 6-membered ring, which is substituted with 0 to 4 substituents selected from the group comprising R16, R17, R18 and R19, and is saturated, unsaturated, or aromatic, and, if heterocyclic, contains one or more heteroatom(s) each and independently selected from N, O and S; and R16, R17, R18 and R19 are individually and independently selected from hydrogen atom, halogen atom, hydroxy, cyano, amino, alkyl, and optionally substituted heteroalkyl.