10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid chloride | 14846-34-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid chloride
• 英文别名: 10,11-dihydro-5H-dibenzocycloheptene-5-carbonyl chloride；10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylcarbonyl chloride；10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonyl chloride；10,11-Dihydro-5H-dibenzocyclohepten-carbonsaeure-(5)-chlorid；Dibenzo<1.4>cycloheptadien-5-carbonylchlorid；Dibenzo1,4-cycloheptadien-5-carbonylchlorid；10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carbonyl chloride；tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaene-2-carbonyl chloride
• CAS: 14846-34-5
• 化学式: C₁₆H₁₃ClO
• mdl: MFCD28119229
• 分子量: 256.732
• InChiKey: GJYMAIMWYXLDMT-UHFFFAOYSA-N

物化性质

• 熔点：
  64-65 °C
• 沸点：
  359.6±31.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid chloride 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 1-<(10,11-dihydro-5H-dibenzocycloheptene-5-yl)methyl>piperazine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017
• 作为产物：
  描述：

  10,11-二氢-5H-二苯并[A,D]环庚烯-5-甲腈 在 氯化亚砜 、 硫酸 作用下， 以 苯 为溶剂， 生成 10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid chloride
  参考文献：
  名称：

  新的精神药物。V.5-氰基和5-羧酰胺基二苯并（A，D）环庚二烯的衍生物。

  摘要：

  DOI：

  10.1021/jm00339a008

文献信息

• Discovery of Novel Quaternary Ammonium Derivatives of (3<i>R</i>)-Quinuclidinol Esters as Potent and Long-Acting Muscarinic Antagonists with Potential for Minimal Systemic Exposure after Inhaled Administration: Identification of (3<i>R</i>)-3-{[Hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane Bromide (Aclidinium Bromide)
  作者：María Prat、Dolors Fernández、M. Antonia Buil、María I. Crespo、Gaspar Casals、Manuel Ferrer、Laia Tort、Jordi Castro、Juan M. Monleón、Amadeu Gavaldà、Montserrat Miralpeix、Israel Ramos、Teresa Doménech、Dolors Vilella、Francisca Antón、Josep M. Huerta、Sonia Espinosa、Manuel López、Sonia Sentellas、Marisa González、Joan Albertí、Victor Segarra、Alvaro Cárdenas、Jorge Beleta、Hamish Ryder

  DOI：10.1021/jm900132z

  日期：2009.8.27

  risk−benefit profile compared with current antimuscarinic agents. A series of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters were synthesized and evaluated. On the basis of its overall profile, (3R)-3-[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidinium bromide) emerged as a candidate for once-daily maintenance treatment of COPD

  这项工作的目的是发现一种新型的长效毒蕈碱型M 3拮抗剂，用于吸入治疗慢性阻塞性肺疾病（COPD），与目前的抗毒蕈碱剂相比，具有潜在的改善的风险效益。合成并评价了一系列新的（3 R）-喹啉醇酯的季铵衍生物。根据其总体情况，（3 R）-3-[羟基（二-2-噻吩基）乙酰基]氧基} -1-（3-苯氧基丙基）-1-氮杂双环[2.2.2]辛烷溴化物（溴化ac啶）成为每日维护一次的候选物治疗COPD。该化合物是有效的毒蕈碱拮抗剂，在体内具有长效作用，并且在人血浆中具有快速水解作用，从而最大程度地减少了诱发类相关的全身性副作用的可能性。溴化阿地铵目前处于III期开发中，用于维持治疗COPD患者。
• 1-[(10,11-Dihydro-5H-dibenzo[a,d]-cyclohepten-5-yl)methyl]-4-substituted
  申请人：G. D. Searle & Co.

  公开号：US04188485A1

  公开（公告）日：1980-02-12

  The invention encompasses 1-[10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)methyl]-4-substituted piperidines and related compounds of the formula ##STR1## and the non-toxic pharmaceutically acceptable acid addition salts thereof; wherein R in each occurrence represents hydrogen, halogen, alkyl radical of 1 to 7 carbon atoms, or trifluoromethyl, alike or different; R.sup.1 is hydrogen or alkyl radical of 1 to 7 carbon atoms; Z is hydroxy or NR.sup.2 R.sup.3 group wherein R.sup.2 and R.sup.3 are each hydrogen or alkyl radical of 1 to 7 carbon atoms or R.sup.2 and R.sup.3 together with the N-atom represent an azamonocyclic ring which contains from 4 to 6 carbon atoms; X is ethylene, vinylene, oxy or thio; and m and n are each alike or different integer from 1 to 4 inclusive; and 1-(2,2-diarylethyl)-4-piperidinols of the formula ##STR2## and the non-toxic pharmaceutically acceptable acid addition salts thereof; wherein Ar is phenyl optionally substituted with one or more halogen or alkyl radical of 1 to 7 carbon atoms, alike or different; Ar.sup.1 is phenyl optionally substituted with one or more halogen or alkyl radical of 1 to 7 carbon atoms alike or different; and R.sup.4 is selected from the group consisting of hydrogen alkyl radical of 1 to 7 carbon atoms, 4-hydroxy-1-(2,2-diphenylethyl)-3-piperidinyl, and 4-oxo-1-(2,2-diphenylethyl)-3-piperidinyl. These compounds possess utility as neuroleptic agents.

  这项发明涵盖了1-[10,11-二氢-5H-二苯并[a,d]环庚烯-5-基)甲基]-4-取代哌啶和相关化合物的结构，以及其非毒性药学上可接受的酸盐；其中每次出现的R代表氢、卤素、1至7个碳原子的烷基基团或三氟甲基，相同或不同；R.sup.1为氢或1至7个碳原子的烷基基团；Z为羟基或NR.sup.2 R.sup.3基团，其中R.sup.2和R.sup.3分别为氢或1至7个碳原子的烷基基团或R.sup.2和R.sup.3与N原子一起代表含有4至6个碳原子的氮杂单环环，X为乙烯、乙烯基、氧基或硫基；m和n分别为1至4的整数，相同或不同；以及1-(2,2-二芳基乙基)-4-哌啶醇的结构和相关非毒性药学上可接受的酸盐；其中Ar为苯基，可选择地取代一个或多个卤素或1至7个碳原子的烷基基团，相同或不同；Ar.sup.1为苯基，可选择地取代一个或多个卤素或1至7个碳原子的烷基基团，相同或不同；以及R.sup.4选自氢、1至7个碳原子的烷基基团、4-羟基-1-(2,2-二苯基乙基)-3-哌啶基和4-氧代-1-(2,2-二苯基乙基)-3-哌啶基。这些化合物具有作为神经阻滞剂的用途。
• [EN] NEW QUATERNIZED QUINUCLIDINE ESTERS<br/>[FR] NOUVEAUX ESTERS DE QUINUCLIDINE QUATERNISES
  申请人：ALMIRALL PRODESFARMA SA

  公开号：WO2005090342A1

  公开（公告）日：2005-09-29

  Compounds of formula (1) wherein the different substituents and/or radicals have the values defined in the claims. The invention also relates to a process for the preparation of said compounds, to pharmaceutical compositions comprising them, as well as to combinations of said compounds with other compounds which are active in the treatment of respiratory, urological or gastrointestinal disorders or diseases. Finally the invention also relates to the use of the compounds of formula (I) for the treatment of respiratory, urological or gastrointestinal disorders or diseases.

  公式（1）中的化合物，其中不同的取代基和/或基团具有权利要求中定义的值。本发明还涉及一种制备所述化合物的方法，包括含有它们的药物组合物，以及含有其他对治疗呼吸道、泌尿系统或消化系统疾病有活性的化合物与所述化合物的组合物。最后，本发明还涉及利用公式（I）的化合物治疗呼吸道、泌尿系统或消化系统疾病的用途。
• Amino pyridine derivatives
  申请人：John Wyeth & Brother Limited

  公开号：US04180670A1

  公开（公告）日：1979-12-25

  Novel 4-pyridinamine derivatives having the formula ##STR1## [where R.sup.1 and R.sup.2 are aryl or heteroaryl (optionally linked together by a lower alkylene bridge) or one of R.sup.1 and R.sup.2 is aryl or heteroaryl and the other of R.sup.1 and R.sup.2 is lower alkyl or ar(lower)alkyl, R.sup.3 and R.sup.4 are each hydrogen or lower alkyl and n is 0 or 1] and their non-toxic acid addition salts are described. They show CNS activity and may be used as antidepressant drugs. Some also show stimulant activity. Novel intermediates having the formula ##STR2## are also described.

  描述了具有以下结构的新型4-吡啶胺衍生物 [其中R.sup.1和R.sup.2是芳基或杂环芳基（可选择通过较低的烷基桥连接在一起），或者R.sup.1和R.sup.2中的一个是芳基或杂环芳基，另一个是较低烷基或芳基（较低）烷基，R.sup.3和R.sup.4分别是氢或较低烷基，n为0或1]，以及它们的无毒酸盐。它们显示中枢神经系统活性，可用作抗抑郁药物。其中一些还显示兴奋活性。还描述了具有以下结构的新型中间体。
• 4-Pyridinamine derivatives
  申请人：John Wyeth & Brother Limited

  公开号：US04243808A1

  公开（公告）日：1981-01-06

  Novel 4-pyridinamine derivatives having the formula ##STR1## and their pharmaceutically acceptable acid addition salts (wherein A is C.sub.1 to C.sub.4 alkylene, each of B.sub.1 and B.sub.2, together with the two carbon atoms joined thereto, forms arylene or heteroarylene, R.sub.3 and R.sub.4 are independently hydrogen or lower alkyl and n is 0 or 1) are described. They show CNS activity and may be used as anti-depressant drugs.

  本发明涉及具有以下公式的新型4-吡啶胺衍生物及其药学上可接受的酸加成盐（其中，A为C.sub.1至C.sub.4烷基，B.sub.1和B.sub.2分别与其结合的两个碳原子一起形成芳基或杂芳基，R.sub.3和R.sub.4独立地表示氢或低烷基，n为0或1）。它们表现出中枢神经系统活性，可以用作抗抑郁药物。