(+/-)-3,4-dihydro-3-methyl-7-nitrosoquinolin-1-(2H)-one | 233272-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (+/-)-3,4-dihydro-3-methyl-7-nitrosoquinolin-1-(2H)-one
• 英文别名: 3-methyl-7-nitro-3,4-dihydro-2H-isoquinolin-1-one
• CAS: 233272-42-9
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: DKFALZDHVIWUNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-3,4-dihydro-3-methyl-7-nitrosoquinolin-1-(2H)-one 在 platinum(IV) oxide 盐酸 、 氢溴酸 、 氢气 、 sodium nitrite 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 5.0h， 生成 7-bromo-3-methyl-3,4-dihydroisoquinolin-1(2H)-one
  参考文献：
  名称：

  Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors

  摘要：

  A series of 3 -alkyl-7 -substituted-1,2,3,4-tetrahydroisoquinolines was synthesized and these compounds were evaluated for their PNMT inhibitory potency and affinity for the (alpha(2)-adrenoceptor. 7-Nitro-, 7-bromo-, 7-aminosulfonyl-, or 7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs that possess a 3-alkyl substituent that is longer than a methyl group showed decreased PNMT inhibitory potency, except for 3-propyl-7-aminosulfonyl-THIQ, which displayed excellent PNMT inhibitory potency. The rank order for selectivity (PNMT vs the alpha(2)-adrenoceptor) is 3 -alkyl -7 -aminosulfonyl-THIQs congruent to 3-alkyl-7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs > 3-alkyl-7-nitro-THlQs > 3-alkyl-7-bromo-THIQs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.015
• 作为产物：
  描述：

  3-甲基-1,2,3,4-四氢异喹啉-1-酮 在 硫酸 、 potassium nitrate 作用下， 生成 (+/-)-3,4-dihydro-3-methyl-7-nitrosoquinolin-1-(2H)-one
  参考文献：
  名称：

  Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors

  摘要：

  A series of 3 -alkyl-7 -substituted-1,2,3,4-tetrahydroisoquinolines was synthesized and these compounds were evaluated for their PNMT inhibitory potency and affinity for the (alpha(2)-adrenoceptor. 7-Nitro-, 7-bromo-, 7-aminosulfonyl-, or 7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs that possess a 3-alkyl substituent that is longer than a methyl group showed decreased PNMT inhibitory potency, except for 3-propyl-7-aminosulfonyl-THIQ, which displayed excellent PNMT inhibitory potency. The rank order for selectivity (PNMT vs the alpha(2)-adrenoceptor) is 3 -alkyl -7 -aminosulfonyl-THIQs congruent to 3-alkyl-7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs > 3-alkyl-7-nitro-THlQs > 3-alkyl-7-bromo-THIQs. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.11.015

文献信息

• [EN] 4-SUBSTITUTED 4, 6-DIALKOXY-CINNOLINE DERIVATIVES AS PHOSPODIESTERASE 10 INHIBITORS FOR THE TREATMENT OF PSYCHIATRIC OR NEUROLOGICAL SYNDROMS<br/>[FR] DERIVES DE 4, 6-DIALKOXY-CINNOLINE SUBSTITUES EN POSITION 4 EN TANT QU'INHIBITEURS DE PHOSPODIESTERASE 10 POUR LE TRAITEMENT DE SYNDROMES PSYCHIATRIQUES OU NEUROLOGIQUES
  申请人：MEMORY PHARM CORP

  公开号：WO2006028957A1

  公开（公告）日：2006-03-16

  The present disclosure relates generally to the field of phosphodiesterase 10 (PDE10) enzyme inhibition by cinnoline compounds of Formulas: (I) and (II); wherein R'-R3 and R15-R18 are as defined herein. Still further, the present invention provides methods for synthesizing compounds with such activity and selectivity, as well as methods of and corresponding pharmaceutical compositions for treating a patient, e.g., mammals, including humans, in need of PDE inhibition. Treatment is preferably for a disease state that involves elevated intracellular PDE10 levels or decreased cAMP and/or cGMP levels, e.g., involving neurological or psychiatric syndromes, especially those states associated with psychoses, most especially schizophrenia or bipolar disorder, obsessive-compulsive disorder, and/or Parkinson’s disease. In particular, such psychoses, obsessive-compulsive disorder, and/or Parkinson’s disease are due at least in part to catabolism of intracellular cAMP and/or cGMP levels by PDE10 enzymes or where such an impaired condition can be improved by increasing cAMP and/or cGMP levels.

  本公开涉及磷酸二酯酶10（PDE10）酶被Formula（I）和（II）的喹啉类化合物抑制；其中R'-R3和R15-R18如本文所定义。此外，本发明提供了合成具有此类活性和选择性的化合物的方法，以及用于治疗需要PDE抑制的患者，例如哺乳动物，包括人类的方法和相应的药物组合物。治疗最好用于涉及细胞内PDE10水平升高或cAMP和/或cGMP水平降低的疾病状态，例如涉及神经系统或精神症候群，尤其是与精神病、强迫症、帕金森病有关的状态。特别是这些精神病、强迫症和/或帕金森病至少部分是由PDE10酶分解细胞内cAMP和/或cGMP水平引起的，或者这种受损状态可以通过增加cAMP和/或cGMP水平来改善。
• Phosphodiesterase 10 inhibitors
  申请人：Arrington Phillip Mark

  公开号：US20070093515A1

  公开（公告）日：2007-04-26

  Provided are certain quinazolines that are PDE10 inhibitors, pharmaceutical compositions, containing the same and processes for preparing the same. Also provided are methods of treating diseases treatable by PDE10 enzyme such as obesity, non-insulin dependent diabetes, schizophrenia or bipolar disorder, obsessive-compulsive disorder, and the like, by administering those certain quinazolines.

  提供了某些喹唑啉类化合物作为PDE10抑制剂，以及含有这些化合物的药物组合物和制备这些化合物的方法。同时，还提供了通过给予这些喹唑啉类化合物治疗可由PDE10酶治疗的疾病（如肥胖症、非胰岛素依赖性糖尿病、精神分裂症或躁郁症、强迫症等）的方法。
• 3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines Display Remarkable Potency and Selectivity as Inhibitors of Phenylethanolamine <i>N-</i>Methyltransferase versus the α₂-Adrenoceptor^1a
  作者：Gary L. Grunewald、Vilas H. Dahanukar、Bee Teoh、Kevin R. Criscione

  DOI：10.1021/jm9807252

  日期：1999.6.1

  3-Hydroxymethyl-1,2,3,4-tetrahydroisoquinoline (4) is a more selective inhibitor (PNMT K-i = 1.1 mu M, alpha(2) K-i = 6.6 mu M, selectivity (alpha(2) K-i/PNMT K-i) = 6.0) of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), with respect to its az-adrenoceptor affinity, than is 3-methyl-1,2,3,4-tetrahydroisoquinoline (2; PNMT K-i = 2.1 mu M, alpha 2 K-i = 0.76 mu M, selectivity = 0.36) or 1,2,3,4-tetrahydroisoquinoline (1, THIQ; PNMT K-i = 9.7 mu M, alpha 2 K-i = 0.35 mu M, selectivity = 0.036). Evaluation of the O-methyl ether derivative of 4 suggested that the 3-hydroxymethyl substituent might be involved in a hydrogen-bond donor-type of interaction at a sterically compact region in the PNMT active site. The directionality of the steric bulk tolerance at both the PNMT active site and the alpha(2)-adrenoceptor appears to be the same. Since the presence of a hydrophilic electron-withdrawing substituent (such as NO2, SO2CH3, or SO2NH2) at the 7-position of THIQ reduced the binding affinity toward the alpha(2)-adrenoceptor, we investigated the combination of both a hydrophilic electron-withdrawing 7-substituent and a S-alkyl substituent on a THIQ nucleus. A synergistic effect in increasing the PNMT-inhibitory potency of the THIQ nucleus and reducing the affinity toward the alpha(2)-adrenoceptor was observed with this 3,7-disubstitution. Remarkably, 7-aminosulfonyl-3-hydroxymethyl-THIQ (12; PNMT K-i = 0.34 mu M, alpha 2 K-i = 1400 mu M, selectivity = 4100) displayed a 23-680-fold enhanced selectivity over the parent compounds 27 (SK&F 29661; PNMT K-i = 0.55 mu M, alpha 2 K-i = 100 mu M, selectivity = 180) and 4 (selectivity = 6.0) and is thus the most selective PNMT inhibitor yet reported.
• [EN] PHOSPHODIESTERASE 10 INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHODIESTÉRASE 10
  申请人：MEMORY PHARM CORP

  公开号：WO2007022280A1

  公开（公告）日：2007-02-22

  [EN] Provided are certain quinazolines of formular (I) or (II) that are PDElO inhibitors, pharmaceutical compositions, containing the same and processes for preparing the same. Also provided are methods of treating diseases treatable by PDElO enzyme such as obesity, non-insulin dependent diabetes, schizophrenia or bipolar disorder, obsessive-compulsive disorder, and the like, by administering those certain quinasolines .
  [FR] La présente invention se rapporte à certaines quinasolines de la formule (I) ou (II) qui sont des inhibiteurs de PDElO, à des compositions pharmaceutiques, contenant les mêmes procédés pour la préparation de ces quinasolines. Cette invention concerne également des procédés de traitement de maladies traitables par l'enzyme PDElO comme l'obésité, les diabètes non insulinodépendants, la schizophrénie ou le trouble bipolaire, les troubles obsessionnels compulsifs, et les pathologies cliniques semblables, en administrant certaines quinasolines .
• Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors
  作者：Gary L. Grunewald、F. Anthony Romero、Alex D. Chieu、Kelcie J. Fincham、Seema R. Bhat、Kevin R. Criscione

  DOI：10.1016/j.bmc.2004.11.015

  日期：2005.2

  A series of 3 -alkyl-7 -substituted-1,2,3,4-tetrahydroisoquinolines was synthesized and these compounds were evaluated for their PNMT inhibitory potency and affinity for the (alpha(2)-adrenoceptor. 7-Nitro-, 7-bromo-, 7-aminosulfonyl-, or 7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs that possess a 3-alkyl substituent that is longer than a methyl group showed decreased PNMT inhibitory potency, except for 3-propyl-7-aminosulfonyl-THIQ, which displayed excellent PNMT inhibitory potency. The rank order for selectivity (PNMT vs the alpha(2)-adrenoceptor) is 3 -alkyl -7 -aminosulfonyl-THIQs congruent to 3-alkyl-7-N-2,2,2-trifluoroethylaminosulfonyl-THIQs > 3-alkyl-7-nitro-THlQs > 3-alkyl-7-bromo-THIQs. (C) 2004 Elsevier Ltd. All rights reserved.