5-[6-methyl-5-[2-methyl-4-[(2-methylpropan-2-yl)oxy]phenyl]pyrimidin-4-yl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole

• 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: 5-[6-methyl-5-[2-methyl-4-[(2-methylpropan-2-yl)oxy]phenyl]pyrimidin-4-yl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole
• 化学式: C₂₁H₂₅N₅O
• 分子量: 363.5
• InChiKey: NFYBLASCABGJKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  5

文献信息

• [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS<br/>[FR] COMPOSÉS HÉTÉROAROMATIQUES ET LEUR UTILISATION COMME LIGANDS DE LA DOPAMINE D1
  申请人：PFIZER

  公开号：WO2014072881A1

  公开（公告）日：2014-05-15

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced β- arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

  本发明部分提供了化合物I的公式：及其药学上可接受的盐和N-氧化物；制备的过程和中间体；以及其组合物和用途。本发明进一步提供了具有减少D1R耐受性的D1激动剂，相对于多巴胺具有减少β-阿雷斯汀招募活性的D1激动剂，当结合到D1R时与D1R的Ser188显著相互作用但与Ser202的相互作用不显著的D1激动剂，当结合到D1R时与D1R的Asp103相互作用较弱并且与Ser198相互作用较弱的D1激动剂，以及它们的用途。
• HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  申请人：Pfizer Inc.

  公开号：EP2917219B1

  公开（公告）日：2017-09-27
• Heteroaromatic Compounds and their Use as Dopamine D1 Ligands
  申请人：PFIZER INC.

  公开号：US20170165270A1

  公开（公告）日：2017-06-15

  The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) and the uses of such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension. The present invention further provides a D1 agonist with reduced D1R desensitization, a D1 agonist with a reduced β-arrestin recruitment activity relative to Dopamine, a D1 agonist interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, a D1 agonist interacting less strongly the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.
• US9617275B2
  申请人：——

  公开号：US9617275B2

  公开（公告）日：2017-04-11