1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one | 246023-58-5

• 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: 1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one
• 英文别名: 2-(2-methyl-4-methoxyphenyl)-3-oxo-butyronitrile；1-cyano-1-(2-methyl-4-methoxyphenyl)propane-2-one；2-(4-Methoxy-2-methylphenyl)-3-oxobutanenitrile
• CAS: 246023-58-5
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: WLKKCZQJEFOXSR-UHFFFAOYSA-N

物化性质

• 沸点：
  311.5±42.0 °C(Predicted)
• 密度：
  1.088±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one 在 一水合肼 、 溶剂黄146 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 反应 40.0h， 生成 N-(1-乙基丙基)-3-(4-甲氧基-2-甲基苯基)-2,5-二甲基吡唑并[1,5-A]嘧啶-7-胺
  参考文献：
  名称：

  The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5- a ]-pyrimidine: A corticotropin-releasing factor (hCRF 1 ) antagonist

  摘要：

  Structure-activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF(1) antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF(1) K-i= 1.0 +/- 0.2 nM (n = 8)) was a potent antagonist of hCRF(1)-coupled adenylate cyclase activity in HEK293 cells (IC50 = 10.0 +/- 0.01 nM versus 10 nM r/hCRF, I? = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286 +/- 63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency lime in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1. 30 mg/kg (po)) was inactive in this lest. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t(1/2), CL and V-d.ss values equal to 46.4 +/- 7.6 h, 0.49 +/- 0.08 L/kg/h and 23.0 +/- 4.2 L/kg, respectively. After oral dosing. the mean C-max, T-max, t(1/2) and bioavailability values were equal to 1260 +/- 290 nM, 0.75 +/- 0.25 h, 45.1 +/- 10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect Liability. (C) 2000 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00271-0
• 作为产物：
  描述：

  1-(bromomethyl)-4-methoxy-2-methylbenzene 在 sodium 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one
  参考文献：
  名称：

  The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5- a ]-pyrimidine: A corticotropin-releasing factor (hCRF 1 ) antagonist

  摘要：

  Structure-activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF(1) antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF(1) K-i= 1.0 +/- 0.2 nM (n = 8)) was a potent antagonist of hCRF(1)-coupled adenylate cyclase activity in HEK293 cells (IC50 = 10.0 +/- 0.01 nM versus 10 nM r/hCRF, I? = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286 +/- 63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency lime in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1. 30 mg/kg (po)) was inactive in this lest. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t(1/2), CL and V-d.ss values equal to 46.4 +/- 7.6 h, 0.49 +/- 0.08 L/kg/h and 23.0 +/- 4.2 L/kg, respectively. After oral dosing. the mean C-max, T-max, t(1/2) and bioavailability values were equal to 1260 +/- 290 nM, 0.75 +/- 0.25 h, 45.1 +/- 10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect Liability. (C) 2000 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00271-0

文献信息

• Salt and crystalline form thereof of a corticotropin releasing factor receptor antagonist
  申请人：Gilligan J. Paul

  公开号：US20050113375A1

  公开（公告）日：2005-05-26

  The present invention provides 4-(bis(2-methoxyethyl)amino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-[1,5-α]-pyrazolo-1,3,5-triazine benzenesulfonate salt and a crystalline polymorph thereof. Further provided are pharmaceutical compositions containing the salt and methods of treating CRF-related disorders using said salt.

  本发明提供了4-（双（2-甲氧基乙基）氨基）-2,7-二甲基-8-（2-甲基-4-甲氧基苯基）-[1,5-α]-吡唑-1,3,5-三嗪苯磺酸盐及其晶体多形。此外，还提供了含有该盐的药物组合物，并使用该盐治疗CRF相关疾病的方法。
• [EN] SALT AND CRYSTALLINE FORM THEREOF OF A CORTICOTROPIN RELEASING FACTOR RECEPTOR ANTAGONIST<br/>[FR] SEL ET FORME CRISTALLINE D'UN ANTAGONISTE DU RECEPTEUR DE LA CORTICOLIBERINE
  申请人：BRISTOL MYERS SQUIBB PHARMA CO

  公开号：WO2005051394A1

  公开（公告）日：2005-06-09

  The present invention provides 4-(bis(2-methoxyethyl)amino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-[1,5-a)-pyrazolo-1,3,5-triazine benzenesulfonate salt and a crystalline polymorph thereof Further provided are pharmaceutical compositions containing the salt and methods of treating CRF-related disorders using said salt.

  本发明提供了4-(双(2-甲氧基乙基)氨基)-2,7-二甲基-8-(2-甲基-4-甲氧基苯基)-[1,5-a)-吡唑并[1,3,5]三嗪]苯磺酸盐及其晶型多形。还提供了含有该盐的制药组合物以及使用该盐治疗CRF相关疾病的方法。
• Tricyclic and heterocyclic derivative compounds and drugs containing these compounds as the active ingredient
  申请人：——

  公开号：US20040072833A1

  公开（公告）日：2004-04-15

  Tri-heterocyclic compound of formula (I) 1 wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1 is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6 etc.; R 3 is carbocyclic ring, heterocyclic ring; and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient. A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer's disease, drug addiction or alcohol dependence syndrome etc.

  式(I)的三异杂环化合物，其中W、X和Y中的每一个为碳或氮；U和Z中的每一个为CR2、NR13、氮、氧、硫等；环A为碳环或杂环；R1为烷基、烯基、炔基、NR4R5、OR6等；R3为碳环或杂环；以及其药学上可接受的盐，制备过程和将其作为活性成分的制药组合物。式(I)的化合物具有垂体促肾上腺皮质激素释放因子受体拮抗活性，对于预防和/或治疗抑郁症、焦虑症、进食障碍、创伤后应激障碍、消化性溃疡、肠易激综合症、阿尔茨海默病、药物成瘾或酒精依赖综合症等具有用途。
• Convergent synthesis of alpha-aryl-beta-ketonitriles
  申请人：——

  公开号：US20030208068A1

  公开（公告）日：2003-11-06

  The present invention relates to processes for the production of &agr;-aryl-&bgr;-ketonitriles, which serve as synthetic intermediates in the preparation of a series of biologically important molecules such as corticotropin releasing factor (CRF) receptor antagonists.

  本发明涉及生产α-芳基-β-酮腈的过程，该过程用作合成中间体，用于制备一系列生物重要分子，例如促肾上腺皮质激素释放因子（CRF）受体拮抗剂。
• Tri-heterocyclic compounds and a pharmaceutical comprising them as an active ingredient
  申请人：Nakai Hisao

  公开号：US20060122392A1

  公开（公告）日：2006-06-08

  Tri-heterocyclic compound of formula (I) wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1 is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6 etc.; R 3 is carbocyclic ring, heterocyclic ring; and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient. A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer's disease, drug addiction or alcohol dependence syndrome etc.

  式(I)的三杂环化合物，其中W、X和Y中的每一个是碳或氮；U和Z中的每一个是CR2、NR13、氮、氧、硫等；一个环是碳环或杂环；R1是烷基、烯基、炔基、NR4R5、OR6等；R3是碳环或杂环；以及其药学上可接受的盐，制备过程和包含它们作为活性成分的药物。式(I)的化合物具有垂体促肾上腺皮质激素释放因子受体拮抗活性，可用于预防和/或治疗抑郁症、焦虑症、进食障碍、创伤后应激障碍、消化性溃疡、肠易激综合征、阿尔茨海默病、药物成瘾或酒精依赖综合征等。