6,7-Dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido-[6,1-a]isoquinolin-4-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6,7-Dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido-[6,1-a]isoquinolin-4-one
• 英文别名: 6,7-Dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4h-pyrimido[6,1-a]isoquinolin-4-one；2-[2,6-di(propan-2-yl)phenoxy]-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one
• 化学式: C₂₆H₃₀N₂O₄
• 分子量: 434.535
• InChiKey: NBRRSNFRTBXBID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

文献信息

• SYSTEM AND METHOD FOR HOMOGENOUS GPCR PHOSPHORYLATION AND IDENTIFICATION OF BETA-2 ADRENERGIC RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Duke University

  公开号：US20190241642A1

  公开（公告）日：2019-08-08

  The disclosure is directed to a G-protein coupled receptor complex. The complex includes (i) a chimeric G protein-coupled receptor (GPCR) comprising a non-native amino acid sequence located within the C-terminus of the GPCR and a synthetic phosphopeptide ligated to the non-native amino acid sequence; and (ii) a β-arrestin (βarr) protein bound to the C-terminus of the GPCR. The disclosure also provides an in vitro method for producing the aforementioned complex, as well as methods for identifying compounds or ligands which bind to and modulate the activity of the complex. Positive allosteric modulators of the β2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of β2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.

  该披露涉及一个G蛋白偶联受体复合物。该复合物包括(i) 一个嵌合G蛋白偶联受体（GPCR），其中包括位于GPCR C-末端内的非天然氨基酸序列和与非天然氨基酸序列连接的合成磷酸肽；以及(ii) 一个结合到GPCR C-末端的β-阻滞蛋白（βarr）。该披露还提供了一种用于生产上述复合物的体外方法，以及用于识别结合并调节复合物活性的化合物或配体的方法。通过筛选DNA编码文库鉴定的β2肾上腺素受体的正向变构调节剂增强β2激动剂的活性，并在治疗阻塞性气道疾病、支气管痉挛或早产劳动中应用。
• Derivatives of pyrimido[6,1-a]isoquinolin-4-one
  申请人：——

  公开号：US20030119813A1

  公开（公告）日：2003-06-26

  The invention provides compounds or salts thereof of the general formula (I): 1 wherein each of R 1 and R 2 independently represents a C 1-6 alkyl or C 2-7 acyl group; X represents OCH 2 or a group CR 3 R 4 ; wherein each of R 3 or R 4 independently represents a hydrogen atom or a C 1-3 alkyl group; R 5 represents a hydrogen atom or a C 1-3 alkyl, C 2-3 alkenyl or C 2-3 alkynyl group; R 6 represents a hydrogen atom or a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, amino, C 1-6 alkylamino, di(C 1-6 ) alkylamino or C 2-7 acylamino group; each of R 7 and R 8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy, C 3-6 cycloalkyl; and R 9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy or C 3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one).

  该发明提供了通式(I)的化合物或其盐： 其中R1和R2分别代表C1-6烷基或C2-7酰基基团；X代表OCH2或CR3R4基团；其中R3或R4分别代表氢原子或C1-3烷基基团；R5代表氢原子或C1-3烷基、C2-3烯基或C2-3炔基团；R6代表氢原子或C1-6烷基、C2-6烯基、C2-6炔基、氨基、C1-6烷基氨基、双(C1-6)烷基氨基或C2-7酰氨基团；R7和R8分别代表氢或卤原子或羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基、C3-6环烷基；R9代表氢或卤原子或羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基或C3-6环烷基。该化合物或其盐可用于治疗哮喘等呼吸系统疾病。该发明的化合物比已知的三氮杂环化合物trequinsin（9,10-二甲氧基-3-甲基-2-间甲苯基亚基-2,3,6,7-四氢-4H-嘧啶并［6,1-a］异喹啉-4-酮）具有更长的作用持续时间。
• FUSED TRI-CYCLIC COMPOUND AS PDE3/PDE4 DUAL INHIBITOR
  申请人：Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

  公开号：EP3822272A1

  公开（公告）日：2021-05-19

  Provided is a fused tri-cyclic compound as PDE3/PDE4 dual inhibitor, and a use thereof in the preparation of drugs for PDE3/PDE4 associated diseases, particularly in medicinal functions such as chronic obstructive pulmonary disease (COPD). Provided are specifically a compound of formula (I) and a pharmaceutically acceptable salt thereof.

  本发明提供了一种作为 PDE3/PDE4 双重抑制剂的融合三环化合物，以及其在制备治疗 PDE3/PDE4 相关疾病，特别是慢性阻塞性肺病（COPD）等药物功能中的用途。具体提供了式(I)化合物及其药学上可接受的盐。
• Drug combination of PDE3/PDE4 inhibitor and muscarinic receptor antagonist
  申请人：VERONA PHARMA PLC

  公开号：US10471063B2

  公开（公告）日：2019-11-12

  The invention provides a composition which comprises (a) a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a muscarinic receptor antagonist.

  本发明提供了一种组合物，其中包含（a）PDE3/PDE4 抑制剂，即 9,10-二甲氧基-2-(2,4,6-三甲基苯基亚氨基)-3-(N-氨基甲酰基-2-氨基乙基)-3,4,6,7-四氢-2H-嘧啶并[6,1-a]异喹啉-4-酮或其药学上可接受的酸加成盐；以及（b）毒蕈碱受体拮抗剂。
• [EN] FUSED TRI-CYCLIC COMPOUND AS PDE3/PDE4 DUAL INHIBITOR<br/>[FR] COMPOSÉ TRI-CYCLIQUE CONDENSÉ EN TANT QUE DOUBLE INHIBITEUR DE PDE3/PDE4<br/>[ZH] 作为PDE3/PDE4双重抑制剂的三并环类化合物
  申请人：CHIA TAI TIANQING PHARMACEUTICAL GROUP CO LTD

  公开号：WO2020011254A1

  公开（公告）日：2020-01-16

  公开了一类作为PDE3/PDE4双重抑制剂的三并环类化合物，及其在制备PDE3/PDE4相关疾病方面的药物的应用，尤其是在如慢性阻塞性肺病(COPD)等方面的药用功能。具体公开了式(Ⅰ)所示化合物及其药学上可接受的盐。