5-Butoxy-2-chlorobenzohydrazide | 1417411-59-6

• 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: 5-Butoxy-2-chlorobenzohydrazide
• 英文别名: 5-butoxy-2-chlorobenzohydrazide
• CAS: 1417411-59-6
• 化学式: C₁₁H₁₅ClN₂O₂
• 分子量: 242.705
• InChiKey: RKBZHWQDHMRQNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-3-chloro-2-methylquinoxaline 、 5-Butoxy-2-chlorobenzohydrazide 以 正丁醇 为溶剂， 生成 8-bromo-1-(5-butoxy-2-chlorophenyl)-4-methyl[1,2,4]triazolo [4,3-a]quinoxaline
  参考文献：
  名称：

  Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement

  摘要：

  Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 mu M. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.

  DOI：

  10.1021/ml500262u
• 作为产物：
  描述：

  2-氯-5-羟基苯甲酸甲酯 在 sodium hydride 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 mineral oil 为溶剂， 反应 0.58h， 生成 5-Butoxy-2-chlorobenzohydrazide
  参考文献：
  名称：

  [EN] 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES
  [FR] DÉRIVÉS DE 1-ARYL-4-MÉTHYL-[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE

  摘要：

  本发明涉及新型的l-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物，作为磷酸二酯酶2（PDE2）的抑制剂，以及在较小程度上作为磷酸二酯酶10（PDE10）的抑制剂或作为磷酸二酯酶2和10的双重抑制剂。该发明还涉及包含这类化合物的药物组合物，用于制备这类化合物和组合物的方法，以及将这类化合物和组合物用于预防和治疗涉及PDE2的疾病或涉及PDE2和PDE10的疾病，如神经和精神疾病，内分泌或代谢性疾病。本发明还涉及可能用于组织中PDE2酶的成像和定量的放射标记化合物，使用正电子发射断层扫描（PET）。该发明还涉及包含这类化合物的组合物，用于制备这类化合物和组合物的方法，将这类化合物和组合物用于体内或体外成像组织、细胞或宿主，并涉及这类化合物的前体。

  公开号：

  WO2013000924A1

文献信息

• [EN] COMBINATIONS COMPRISING PDE 2 INHIBITORS SUCH AS 1-ARYL-4-METHYL- [1,2,4] TRIAZOLO [4,3-A] QUINOXALINE COMPOUNDS AND PDE 10 INHIBITORS FOR USE IN THE TREATMENT OF NEUROLOGICAL OR METABOLIC DISORDERS<br/>[FR] COMBINAISONS COMPRENANT DES INHIBITEURS DE LA PDE 2 TELS QUE DES COMPOSÉS 1-ARYL-4-MÉTHYL-[1, 2, 4] TRIAZOLO [4, 3-A]-QUINOXALINE ET DES INHIBITEURS DE LA PDE 10 POUR UTILISATION DANS LE TRAITEMENT DE TROUBLES NEUROLOGIQUES OU MÉTABOLIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014001314A1

  公开（公告）日：2014-01-03

  The present invention relates to combinations of phosphodiesterase 2 (PDE2) inhibitors with inhibitors of phosphodiesterase 10 (PDE 10). In particular, the invention relates to combinations of 1-aryl-4- methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives which have been found to inhibit phosphodiesterase 2 (PDE2), with inhibitors of phosphodiesterase 10 (PDE10). Particular PDE10 inhibitors are selected from the group of MP-10, PQ-10, TP-10, papaverine, and the compounds disclosed in WO 2011/051342 and in WO 2011/110545. The invention is also directed to pharmaceutical compositions comprising such combinations, to processes for preparing such compositions, to the use of PDE2 inhibitors, in particular of 1- aryl-4-methyl- [1,2,4]triazolo[4,3-a]-quinoxaline derivatives for the potentiation of said PDE10 inhibitors, and to the use of said PDE10 inhibitors for the potentiation of the effect of said PDE2 inhibitors, in particular, 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives, and to the use of such combinations and compositions for the prevention and treatment of disorders in which PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases.

  本发明涉及磷酸二酯酶2（PDE2）抑制剂与磷酸二酯酶10（PDE 10）抑制剂的组合物。具体地，本发明涉及已被发现能够抑制磷酸二酯酶2（PDE2）的1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物与磷酸二酯酶10（PDE10）抑制剂的组合物。特定的PDE10抑制剂选自MP-10、PQ-10、TP-10、罂粟碱以及WO 2011/051342和WO 2011/110545中披露的化合物。本发明还涉及包含这种组合物的药物组合物、制备这种组合物的工艺、使用PDE2抑制剂，特别是1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物来增强所述PDE10抑制剂的作用，以及使用所述PDE10抑制剂来增强所述PDE2抑制剂的作用，特别是1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物，以及使用这种组合物和组合物预防和治疗涉及PDE2和PDE10的疾病，如神经和精神疾病以及内分泌或代谢性疾病。
• Pyrido[4,3-<i>e</i>][1,2,4]triazolo[4,3-<i>a</i>]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors
  作者：Frederik J. R. Rombouts、Gary Tresadern、Peter Buijnsters、Xavier Langlois、Fulgencio Tovar、Thomas B. Steinbrecher、Greet Vanhoof、Marijke Somers、José-Ignacio Andrés、Andrés A. Trabanco

  DOI：10.1021/ml500463t

  日期：2015.3.12

  A novel series of pyrido[4,3-e][1,2,4]triazolo-[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor p or occupancy data are given for two representative compounds 6 and 12.
• 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES
  申请人：Janssen Pharmaceutica, N.V.

  公开号：EP2723744B1

  公开（公告）日：2016-03-23
• COMBINATIONS COMPRISING 4-METHYL-[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE COMPOUNDS AS PDE 2 INHIBITORS AND PDE 10 INHIBITORS FOR USE IN THE TREATMENT OF NEUROLOGICAL OR METABOLIC DISORDERS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2863909B1

  公开（公告）日：2020-11-04
• COMBINATIONS COMPRISING PDE 2 INHIBITORS SUCH AS 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO-[4,3-A]]QUINOXALINE COMPOUNDS AND PDE 10 INHIBITORS FOR USE IN THE TREATMENT OF NEUROLOGICAL OF METABOLIC DISORDERS
  申请人：Janssen Pharmaceutica NV

  公开号：US20150366873A1

  公开（公告）日：2015-12-24

  The present invention relates to combinations of phosphodiesterase 2 (PDE2) inhibitors with inhibitors of phosphodiesterase 10 (PDE10). In particular, the invention relates to combinations of 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives which have been found to inhibit phosphodiesterase 2 (PDE2), with inhibitors of phosphodiesterase 10 (PDE10). Particular PDE10 inhibitors are selected from the group of MP-10, PQ-10, TP-10, papaverine, and the compounds disclosed in WO 2011/051324 and in WO 2011/110545. The invention is also directed to pharmaceutical compositions comprising such combinations, to processes for preparing such compositions, to the use of PDE2 inhibitors, in particular of 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives for the potentiation of said PDE10 inhibitors, and to the use of said PDE10 inhibitors for the potentiation of the effect of said PDE2 inhibitors, in particular, 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives, and to the use of such combinations and compositions for the prevention and treatment of disorders in which PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases.