PD 123319 bistrifluoroacetate | 136676-91-0

• 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: PD 123319 bistrifluoroacetate
• 英文别名: (S)-1-<<4-(dimethylamino)-3-methylphenyl>methyl>-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo<4,5-c>pyridine-6-carboxylic acid, difluoroacetate salt；(S)-1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo-[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate；S-(+)-1-[(4-(dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo [4,5-c]pyridine-6-carboxylic acid di(trifluoroacetate)salt；S-(+)-1-[(4-(dimethylamino)-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid di(trifluoroacetate)；(S)-1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid；PD 123,319 ditrifluoroacetate；1-[[4-(DiMethylaMino)-3-Methylphenyl]Methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-iMidazo[4,5-c]pyridine-6-carboxylicacidditrifluoroacetate；(6S)-1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(2,2-diphenylacetyl)-6,7-dihydro-4H-imidazo[4,5-c]pyridine-6-carboxylic acid;2,2,2-trifluoroacetic acid
• CAS: 136676-91-0
• 化学式: 2C₂HF₃O₂*C₃₁H₃₂N₄O₃
• 分子量: 736.668
• InChiKey: ODNCUUDQKVCVBG-JCOPYZAKSA-N

物化性质

• 溶解度：
  在水中的溶解度为10mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  10

安全信息

• 安全说明：
  S26
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

制备方法与用途

生物活性

PD 123319 ditrifluoroacetate 是一种有效的、选择性的 AT2 血管紧张素 II 受体拮抗剂，其 IC50 值为 34 nM。

靶点

IC50: 34 nM (AT2 Receptor)

体外研究

PD 123319 在多种组织中被证明能够区分血管紧张素 II 的两个亚类受体。利用标记有放射性同位素 (^{125}) I-AII 的膜片腺皮质细胞显示，第一个类别（对 DuP-753 敏感）大约占总 AII 结合位点的 85%，其亲和力较高 (IC50 约为 92.9 nM)，而 PD-123319 对此结合位点没有影响。第二个类别则对 PD-12339 更敏感，IC50 值约为 6.9 nM，并且其亲和力远低于 DuP-753 (IC50 约为 10 μM)。

反应信息

• 作为产物：
  描述：

  3-(3-甲基-4-硝基苄基)-L-组氨酸二盐酸 在 镍 盐酸 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 80.0h， 生成 PD 123319 bistrifluoroacetate
  参考文献：
  名称：

  Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype

  摘要：

  Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace I-125-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.

  DOI：

  10.1021/jm00115a014

文献信息

• Synthesis and structure-activity relationships of a novel series of non-peptide angiotensin II receptor binding inhibitors specific for the AT2 subtype
  作者：C. John Blankley、John C. Hodges、Sylvester R. Klutchko、Richard J. Himmelsbach、Alexander Chucholowski、Cleo J. Connolly、Sandra J. Neergaard、Michael S. Van Nieuwenhze、Alan Sebastian

  DOI：10.1021/jm00115a014

  日期：1991.11

  Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace I-125-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.