N-[4-(3-chloro-4-methoxy-benzylamino)-8-(2-hydroxy-ethyl)-7-methoxy-quinazolin-6-yl]-propionamide | 1007308-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-[4-(3-chloro-4-methoxy-benzylamino)-8-(2-hydroxy-ethyl)-7-methoxy-quinazolin-6-yl]-propionamide
• 英文别名: N-(4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-yl)propionamide；N-[4-[(3-chloro-4-methoxyphenyl)methylamino]-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-yl]propanamide
• CAS: 1007308-30-6
• 化学式: C₂₂H₂₅ClN₄O₄
• 分子量: 444.918
• InChiKey: OXGSPQPAZQTQCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[4-(3-chloro-4-methoxy-benzylamino)-8-(2-hydroxy-ethyl)-7-methoxy-quinazolin-6-yl]-propionamide 在 咪唑 、 盐酸 、 甲醇 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 8-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N4-(3-chloro-4-methoxybenzyl)-7-methoxyquinazoline-4,6-diamine
  参考文献：
  名称：

  WO2008/20711

  摘要：

  公开号：
• 作为产物：
  描述：

  N-[4-(3-chloro-4-methoxy-benzylamino)-7-methoxy-8-(2-oxo-ethyl)-quinazolin-6-yl]-propionamide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 N-[4-(3-chloro-4-methoxy-benzylamino)-8-(2-hydroxy-ethyl)-7-methoxy-quinazolin-6-yl]-propionamide
  参考文献：
  名称：

  Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction

  摘要：

  In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.108

文献信息

• Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533)
  作者：Hojin Choi、Jaekwang Lee、Young Hoon Kim、Dai Sig Im、In-Chang Hwang、Soo Jin Kim、Seung Kee Moon、Hong Woo Lee、Sung Sook Lee、Soon Kil Ahn、Sang Woong Kim、Nam Song Choi、Kyung Joo Lee

  DOI：10.1016/j.bmcl.2009.10.071

  日期：2010.1

  In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking of this metabolic hot spot led to discovery of 10 (CKD533) which is highly potent, selective and orally efficacious in conscious rabbit model for erectile dysfunction and now is undergoing preclinical toxicology study. (C) 2009 Elsevier Ltd. All rights reserved.
• [EN] QUINAZOLINE DERIVATIVE AS PHOSPHODIESTERASE INHIBITOR AND A PROCESS FOR PREPARING THE SAME<br/>[FR] DÉRIVÉ DE QUINAZOLINE COMME INHIBITEUR DE PHOSPHODIESTERASE ET PROCÉDÉ D'ÉLABORATION CORRESPONDANT
  申请人：CHONG KUN DANG PHARM CORP

  公开号：WO2008020711A1

  公开（公告）日：2008-02-21

  [EN] The present invention relates to a quinazoline derivative, a preparation method thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, a hydrate thereof, a pharmaceutical composition comprising the same and use thereof as a therapeutic agent. The present inveniont relates to a quinazoline derivative exhibiting inhibitory activity against C
  [FR] Dérivé de quinazoline et procédé d'élaboration correspondant, sel pharmaceutiquement acceptable correspondant, solvate correspondant, hydrate correspondant, composition pharmaceutique renfermant ce produit, et utilisation correspondante comme agent thérapeutique. Dérivé de quinazoline à activité inhibitrice sur la phosphodiestérase V (PDE 5)
• [EN] AGENT FOR PREVENTION OR TREATMENT OF BENIGN PROSTATIC HYPERPLASIA COMPRISING A QUINAZOLINE DERIVATIVE<br/>[FR] AGENT DE PRÉVENTION OU DE TRAITEMENT D'HYPERPLASIE PROSTATIQUE BÉNIGNE, COMPRENANT UN DÉRIVÉ DE QUINAZOLINE
  申请人：CHONG KUN DANG PHARM CORP

  公开号：WO2011068288A1

  公开（公告）日：2011-06-09

  The present invention provides a prophylactic or therapeutic agent for benign prostatic hyperplasia (BPH) and accompanying lower urinary tract symptoms (LUTS), comprising a quinazoline derivative as an active ingredient. Further, the present invention provides a composition comprising a quinazoline derivative for use in the treatment or prevention of BPH and LUTS, and a method for preventing or treating BPH and LUTS, including administering an agent or a composition comprising a quinazoline derivative to a mammal including a human. The BPH prophylactic or therapeutic agent or composition ofthe present invention has excellent PDE5 inhibitory effects, exhibits low inhibitory activity on PDE6 and PDE11 at a dose exhibiting PDE5 inhibitory activity, thus providing less side effects, has a moderate blood half-life as compared to other PDE5 inhibitors and therefore can exert sufficient medicinal efficacy even with single administration/day without risk of drug accumulation,thus providing increased drug compliance and excellent metabolic stability.
• WO2008/20711
  申请人：——

  公开号：——

  公开（公告）日：——
• Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction
  作者：Young Hoon Kim、Hojin Choi、Jaekwang Lee、In-Chang Hwang、Seung Kee Moon、Soo Jin Kim、Hong Woo Lee、Dai Sig Im、Sung Sook Lee、Soon Kil Ahn、Sang Woong Kim、Cheol Kyu Han、Jeong Hyeok Yoon、Kyung Joo Lee、Nam Song Choi

  DOI：10.1016/j.bmcl.2008.09.108

  日期：2008.12

  In an effort to minimize side effects associated with low selectivity against PDE isozymes, we have successfully identified a series of 6,7,8-substituted quinzaolines as potent inhibitors of PDE5 with high level of isozyme selectivity, especially against PDE6 and PDE11. PDE5 potency and isozyme selectivity of quinazolines were greatly improved with substitutions both at 6- and 8-position. The synthesis, structure activity relationships and in vivo efficacy of this novel series of potent PDE5 inhibitors are described. (C) 2008 Elsevier Ltd. All rights reserved.