Iodocaramiphen | 135569-31-2

• 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: Iodocaramiphen
• 英文别名: 2-(diethylamino)ethyl 1-(p-iodophenyl)cyclopentanecarboxylate；Cyclopentanecarboxylic acid, 1-(4-iodophenyl)-, 2-(diethylamino)ethyl ester；2-(diethylamino)ethyl 1-(4-iodophenyl)cyclopentane-1-carboxylate
• CAS: 135569-31-2
• 化学式: C₁₈H₂₆INO₂
• 分子量: 415.314
• InChiKey: ILEKPVSEMHSRPU-UHFFFAOYSA-N

物化性质

• 沸点：
  441.4±35.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Iodocaramiphen 在 ammonium ⁷⁶Br-bromide 、 2,5-二羟基苯甲酸 、 copper(II) sulfate 、 溶剂黄146 、 柠檬酸 、 维生素 C 作用下， 反应 1.0h， 生成 <76Br>bromocaramiphen
  参考文献：
  名称：

  Synthesis of a potential M1 muscarinic agent [76Br]bromocaramiphen

  摘要：

  [Br-76]bromocaramiphen was prepared from the iodo-analogue by a Cu+ nucleophilic bromodeiodination exchange. The radiolabelling yield was 40-45%. The radiochemical and chemical purities assessed by radio-TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1-phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyclopentane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the polls tissues indicated that there was still 92% of unchanged radiotracer 30 min p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pens, the colter, the striatum and the cerebellum. These data suggest that [Br-76]bromocaramiphen is not a potential probe for investigating the status of central M(1) muscarinic receptors because of its high lipophilicity (log P-7.4 = 2.4) and its affinity for sigma sites.

  DOI：

  10.1002/(sici)1099-1344(199605)38:5<471::aid-jlcr854>3.0.co;2-q
• 作为产物：
  描述：

  1-(对氨基苯基)环戊烷羧酸 在 盐酸 、 氯化亚砜 、 potassium iodide 、 sodium nitrite 作用下， 以 甲苯 为溶剂， 反应 19.0h， 生成 Iodocaramiphen
  参考文献：
  名称：

  Synthesis of a potential M1 muscarinic agent [76Br]bromocaramiphen

  摘要：

  [Br-76]bromocaramiphen was prepared from the iodo-analogue by a Cu+ nucleophilic bromodeiodination exchange. The radiolabelling yield was 40-45%. The radiochemical and chemical purities assessed by radio-TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1-phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyclopentane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the polls tissues indicated that there was still 92% of unchanged radiotracer 30 min p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pens, the colter, the striatum and the cerebellum. These data suggest that [Br-76]bromocaramiphen is not a potential probe for investigating the status of central M(1) muscarinic receptors because of its high lipophilicity (log P-7.4 = 2.4) and its affinity for sigma sites.

  DOI：

  10.1002/(sici)1099-1344(199605)38:5<471::aid-jlcr854>3.0.co;2-q

文献信息

• Synthesis and biological evaluation of iodine-125 iodocaramiphen. A potential M1 muscarinic imaging agent for SPECT
  作者：Daniel W. McPherson、F. F. Russ Knapp、Robert L. Hudkins

  DOI：10.1002/jlcr.2580340306

  日期：1994.3

  Iodocaramiphen (2) is a selective muscarinic antagonist which binds in vitro with high affinity and selectivity to the M1 subtype of the muscarinic receptor. We report the synthesis of iodine-125 labeled iodocaramiphen ([125I]-2) via a tributylstannyl intermediate (3) in 50% radiochemical yield with a specific activity greater than 1000 mCi/μmol. Biodistribution studies in female Fischer rats demonstrated that [125I]-2 had significant cerebral localization (0.7% injected dose/gram) at 60 minutes post injection. The uptake of activity washed out rapidly from the brain, however, and did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors. In addition, preinjection with (±)-QNB (5 mg/kg) blocked uptake of approximately 25% of the injected radiolabel in the brain at 2 hours. The non-selectivity of 2 toward muscarinic receptors in vivo may result from the metabolism of 2 by various esterases or the affinity of 2 for sigma sites in the brain.

  碘卡马吡芬（2）是一种选择性毒蕈碱拮抗剂，在体外与毒蕈碱受体M1亚型结合，具有高亲和力和选择性。我们报告了碘-125标记的碘卡马吡芬（[125I]-2）通过三丁基锡中间体（3）的合成，放射化学收率为50%，比活度大于1000 mCi/μmol。对雌性费舍尔大鼠的生物分布研究表明，[125I]-2在注射后60分钟具有显著的脑定位（注射剂量/克为0.7%）。然而，放射性物质从大脑中迅速洗脱，并未在富含毒蕈碱受体的脑区域中表现出特异性摄取。此外，注射前用（±）-QNB（5 mg/kg）阻断约25%的注射放射性标记在2小时后的脑内摄取。2对体内毒蕈碱受体的非选择性可能是由于2被各种酯酶代谢或2对大脑中sigma位点的亲和力所致。
• Muscarinic receptor binding profile of para-substituted caramiphen analogs
  作者：Robert L. Hudkins、Diane L. DeHaven-Hudkins、James F. Stubbins

  DOI：10.1021/jm00114a005

  日期：1991.10

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).
• <i>para</i>-C–H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst
  作者：Yutaro Saito、Yasutomo Segawa、Kenichiro Itami

  DOI：10.1021/jacs.5b02052

  日期：2015.4.22

  A highly para-selective aromatic C-H borylation has been accomplished. By a new iridium catalyst bearing a bulky diphosphine ligand, Xyl-MeO-BIPHEP, the C-H borylation of monosubstituted benzenes can be affected with para-selectivity up to 91%. This catalytic system is quite different from the usual iridium catalysts that cannot distinguish meta- and para-C-H bonds of monosubstituted benzene derivatives, resulting in the preferred formation of meta-products. The para-selectivity increases with increasing bulkiness of the substituent on the arene, indicating that the regioselectivity of the present reaction is primarily controlled by steric repulsion between substrate and catalyst. Caramiphen, an anticholinergic drug used in the treatment of Parkinsons disease, was converted into five derivatives via our para-selective borylation. The present [Ir(cod)OH](2)/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, para-selective, aromatic C-H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.
• Synthesis of a potential M1 muscarinic agent [76Br]bromocaramiphen
  作者：V. Strijckmans、D. H. Hunter、F. Dolle、C. Coulon、C. Loc'h、B. Mazière

  DOI：10.1002/(sici)1099-1344(199605)38:5<471::aid-jlcr854>3.0.co;2-q

  日期：1996.5

  [Br-76]bromocaramiphen was prepared from the iodo-analogue by a Cu+ nucleophilic bromodeiodination exchange. The radiolabelling yield was 40-45%. The radiochemical and chemical purities assessed by radio-TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1-phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyclopentane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the polls tissues indicated that there was still 92% of unchanged radiotracer 30 min p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pens, the colter, the striatum and the cerebellum. These data suggest that [Br-76]bromocaramiphen is not a potential probe for investigating the status of central M(1) muscarinic receptors because of its high lipophilicity (log P-7.4 = 2.4) and its affinity for sigma sites.