(4aS-cis)-1,9,10,10a-tetrahydro-4a(4H)-phenanthrene carboxylic acid | 149495-92-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4aS-cis)-1,9,10,10a-tetrahydro-4a(4H)-phenanthrene carboxylic acid
• 英文别名: Cis-1,9,10,10a-tetrahydro-4a(4H) phenanthrene carboxylic acid；(4aS,10aS)-1,9,10,10a-tetrahydro-4a(4H)-phenanthrenecarboxylic acid；(4aS,10aS)-4,9,10,10a-tetrahydro-1H-phenanthrene-4a-carboxylic acid
• CAS: 149495-92-1
• 化学式: C₁₅H₁₆O₂
• 分子量: 228.291
• InChiKey: VPIKHFWERATWBS-DOMZBBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4aS-cis)-1,9,10,10a-tetrahydro-4a(4H)-phenanthrene carboxylic acid 在 钯 作用下， 以 甲醇 为溶剂， 以88%的产率得到Cis-1,3,4,9,10,10a-Hexahydro-4a(2H)phenanthrene-carboxylic acid
  参考文献：
  名称：

  Tetracyclic amines having pharmaceutical activity

  摘要：

  本发明涉及新型四环胺及其衍生物，可作为药物代理使用，涉及其生产方法，包括这些化合物和药物可接受的载体的制药组合物，以及制药治疗方法。本发明的化合物可用于治疗神经退行性疾病，包括脑血管疾病。

  公开号：

  US05141934A1
• 作为产物：
  描述：

  cis-1,9,10,10a-tetrahydro-4a(4H)-phenanthrenecarboxylic acid 生成 (4aS-cis)-1,9,10,10a-tetrahydro-4a(4H)-phenanthrene carboxylic acid
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of 4a-phenanthrenamine derivatives acting at the phencyclidine binding site of the N-methyl-D-aspartate receptor complex

  摘要：

  A novel series of octahydrophenanthrenamines and their heterocyclic analogues have been synthesized as potential noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor complex. The compounds were evaluated for their affinity at the phencyclidine (PCP) binding site by determining their ability to displace [H-3]TCP from crude rat brain synaptic membranes. A wide range of affinities were observed, with the most potent analogs possessing IC50's equivalent to that of the reference agent MK-801 (3,dizocilpine). NMDA antagonist activity was demonstrated by prevention of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Selected compounds were also studied in vivo to determine their ability to prevent the lethal effects of systemically injected NMDA in the mouse. In general, the SAR of the phenanthrenamine series may be summarized as follows: (a) for the amino group at C4a, NHMe > NH2 > NHEt much-greater-than NC5H10; (b) for the B-ring substitution, X = CH2 > S > 0; (c) unsaturation of the C ring decreases receptor affinity; (d) cis-ring fusion between the B and C rings is desirable; (e) 6-hydroxy or 6-methoxy substitution of the phenanthrenamine system identified an additional hydrogen bonding interaction that substantially increased receptor affinity; (f) spiro analogues (such as 55, IC50 = 3400 nM), which altered the point of attachment of the C ring, caused a substantial reduction in PCP-site affinity. Molecules from this series were useful for refining a pharmacophore model consistent with previous models of the PCP site. In this model, the (R)-(+)-phenanthrenamine 13 superimposes closely onto MK-801 (3), and the angular 4a-amino group is believed to hydrogen bond with a putative receptor site atom. In the phenanthrenamine and thiaphenanthrenamine series, the (R)-(+)-enantiomers (9, 13, and 44) are more potent by approximately 5-10-fold than their corresponding (S)-(-)-enantiomers with respect to their affinity for the PCP site, their ability to prevent accumulation of [Ca-45(2+)] in cultured neuronal cells, and their protection against the lethal effects of NMDA in mice. In general, there was no separation between the dose that prevented NMDA lethality and the dose that produced ataxia in mice, except in the case of the thiaphenanthrenamines 41 and 43. We have not yet obtained evidence that this small separation in activity offers a therapeutic advantage in the treatment of cerebral ischemia or other neurodegenerative disorders.

  DOI：

  10.1021/jm00066a007

文献信息

• Polycyclic amines useful as cerebrovascular agents
  申请人：——

  公开号：US05071853A1

  公开（公告）日：1991-12-10

  A novel series of polycyclic amines, derivatives, methods of making the compounds, novel intermediates, compositions containing them, and methods for using them in the treatment and prevention of cerebrovascular disorders are disclosed.

  揭示了一种新的多环胺类化合物系列，其衍生物，制备这些化合物的方法，新的中间体，含有它们的组合物，以及在治疗和预防脑血管疾病中使用它们的方法。
• US5071853A
  申请人：——

  公开号：US5071853A

  公开（公告）日：1991-12-10
• US5180736A
  申请人：——

  公开号：US5180736A

  公开（公告）日：1993-01-19
• US5141934A
  申请人：——

  公开号：US5141934A

  公开（公告）日：1992-08-25
• US5276053A
  申请人：——

  公开号：US5276053A

  公开（公告）日：1994-01-04