2-[4-[6,7-diethoxy-2,3-bis(hydroxymethyl)-1-naphthalenyl]-2-pyridinyl]-4-(3-pyridinyl)-1(2H)-phthalazinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-[4-[6,7-diethoxy-2,3-bis(hydroxymethyl)-1-naphthalenyl]-2-pyridinyl]-4-(3-pyridinyl)-1(2H)-phthalazinone
• 英文别名: T-2585；1-[2-{4-(3-pyridyl)-1(2H)-phthalazinon-2-yl}-4-pyridyl]-2,3-bis(hydroxymethyl)-6,7-diethoxynaphthalene；2-[4-(6,7-Diethoxy-2,3-bis-hydroxymethyl-naphthalen-1-yl)-pyridin-2-yl]-4-pyridin-3-yl-2H-phthalazin-1-one; hydrochloride；2-[4-[6,7-diethoxy-2,3-bis(hydroxymethyl)naphthalen-1-yl]pyridin-2-yl]-4-pyridin-3-ylphthalazin-1-one
• 化学式: C₃₄H₃₀N₄O₅
• 分子量: 574.636
• InChiKey: OEZADIAHVKNQKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯吡啶-4-甲醛 在 正丁基锂 、 三氟化硼乙醚 、 一水合肼 、 溶剂黄146 、 红铝 作用下， 以 四氢呋喃 、 乙二醇 、 甲苯 、 乙腈 、 xylene 为溶剂， 反应 13.0h， 生成 2-[4-[6,7-diethoxy-2,3-bis(hydroxymethyl)-1-naphthalenyl]-2-pyridinyl]-4-(3-pyridinyl)-1(2H)-phthalazinone
  参考文献：
  名称：

  Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives

  摘要：

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).

  DOI：

  10.1021/jm980314l

文献信息

• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
  申请人：Dahmann Georg

  公开号：US20130023502A1

  公开（公告）日：2013-01-24

  The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R 1 , R 2 , R 4 , R 3 , R 5 and R 6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.

  该发明涉及公式1中的新取代吡啶基嘧啶化合物， 其中环A是一个含有五个成员的饱和或不饱和碳环，该环可选地包含一个、两个或三个异原子，每个异原子独立地选自N、S和O组成， 其中R1、R2、R4、R3、R5和R6如权利要求书中所定义，并且环A进一步可选地被一个或两个进一步取代基取代，以及上述化合物的药用盐、二对映体、对映体、消旋体、水合物和溶剂化合物。
• NEW COMPOUNDS
  申请人：HAUEL Norbert

  公开号：US20100240669A1

  公开（公告）日：2010-09-23

  The present invention relates to the compounds of general formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X are defined as described hereinafter, the enantiomers, the diastereomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable properties, the preparation thereof, the medicaments containing the pharmacologically effective compounds, the preparation thereof and the use thereof.

  本发明涉及一般式I的化合物，其中n、R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和X的定义如下所述，其对映体、非对映体、混合物及其盐，特别是其与有机或无机酸或碱形成的生理上可接受的盐，具有有价值的性质，其制备方法，含有药理学有效化合物的药物，其制备方法和用途。
• 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS
  申请人：Parion Sciences, Inc.

  公开号：US20140170244A1

  公开（公告）日：2014-06-19

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下式的化合物： 或其药用可接受的盐，用作钠通道阻滞剂，以及含有相同化合物的组合物，制备相同化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。