tert-butyl 2-(2-methyl-1H-indol-1-yl)acetate | 1000295-87-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-(2-methyl-1H-indol-1-yl)acetate
• 英文别名: Tert-butyl 2-(2-methylindol-1-yl)acetate
• CAS: 1000295-87-3
• 化学式: C₁₅H₁₉NO₂
• mdl: MFCD23310274
• 分子量: 245.321
• InChiKey: PLKZKLWKHAHRCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(2-methyl-1H-indol-1-yl)acetate 在 N-甲基吗啉 、 aluminum (III) chloride 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 溶剂黄146 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 2-(3-(3-benzyl-4-oxo-3,4-dihydrophthalazin-1-yl)-2-methyl-1H-indol-1-yl)-N,N-dimethylacetamide
  参考文献：
  名称：

  Diazine Indole Acetic Acids as Potent, Selective, and Orally Bioavailable Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases

  摘要：

  New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents, 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.

  DOI：

  10.1021/jm300007n
• 作为产物：
  描述：

  2-甲基吲哚 、 溴乙酸叔丁酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 tert-butyl 2-(2-methyl-1H-indol-1-yl)acetate
  参考文献：
  名称：

  WO2008/818

  摘要：

  公开号：

文献信息

• Novel heterocyclic amide derivatives and their use as dopamine D3 receptor ligands
  申请人：Hendrix A. James

  公开号：US20070142351A1

  公开（公告）日：2007-06-21

  The invention relates to heterocyclic substituted amide derivatives that display selective binding to dopamine D 3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D 3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, Neuroleptic-Induced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D 3 receptors.

  本发明涉及杂环取代酰胺衍生物，其显示对多巴胺D3受体的选择性结合。另一方面，本发明涉及一种治疗中枢神经系统疾病的方法，该疾病与需要该治疗的患者的多巴胺D3受体活性有关，包括向受试者投予所述化合物的治疗有效量以缓解该疾病。这些化合物可以治疗的中枢神经系统疾病包括精神病性障碍、物质依赖、物质滥用、运动障碍（如帕金森病、帕金森综合征、神经阻滞剂引起的迟发性运动障碍、吉尔·德·拉·图雷特综合征和亨廷顿病）、痴呆、焦虑症、睡眠障碍、昼夜节律障碍和情绪障碍。本发明还涉及制备上述化合物的过程，以及将这些化合物用作多巴胺D3受体成像剂的方法。
• Fluorinated indoleamides useful as ligands of the ORL-1 receptor
  申请人：NIKEM RESEARCH S.R.L.

  公开号：EP1873150A1

  公开（公告）日：2008-01-02

  New ligands for the ORL-1 receptor are described, useful for antagonising the activity of said receptors in a patient in need thereof, and for preventing and treating illnesses dependent on the activation of this receptor. The new compounds conform to structural formula (I) In formula (I) inter alia, at least one of the two R4 substituents is a fluorine atom and at least one among R2 and R3 is a group -(CH2)n-CONRaRb, where R1, R2, R3, R4, n, Ra, Rb are defined in the description.

  本文描述了 ORL-1 受体的新配体，可用于拮抗有需要的患者体内上述受体的活性，以及预防和治疗依赖于该受体激活的疾病。这些新化合物符合结构式 (I) 在式 (I) 中，两个 R4 取代基中至少有一个是氟原子，R2 和 R3 中至少有一个是基团-(CH2)n-CONRaRb，其中 R1、R2、R3、R4、n、Ra、Rb 的定义见说明。
• WO2008/818
  申请人：——

  公开号：——

  公开（公告）日：——
• US7550469B2
  申请人：——

  公开号：US7550469B2

  公开（公告）日：2009-06-23
• [EN] FLUORINATED INDOLEAMIDES USEFUL AS LIGANDS OF THE ORL-1 RECEPTOR<br/>[FR] INDOLÉAMIDES FLUORÉS UTILES COMME LIGANDS DU RÉCEPTEUR ORL-1
  申请人：BRANE DISCOVERY S R L

  公开号：WO2008000818A1

  公开（公告）日：2008-01-03

  [EN] New ligands for the ORL-1 receptor are described, useful for antagonising the activity of said receptors in a patient in need thereof, and for preventing and treating illnesses dependent on the activation of this receptor. The new compounds conform to structural formula (I). In formula (I) inter alia, at least one of the two R₄ substituents is a fluorine atom and at least one among R2 and R3 is a group -(CH₂)_n-CONR_aR_b, where R1, R2, R3, R4, n, R_a, R_b are defined in the description.
  [FR] L'invention concerne de nouveaux ligands pour le récepteur ORL-1, utiles pour jouer le rôle d'antagonistes de l'activité desdits récepteurs chez un patient en ayant besoin, et pour prévenir et traiter des maladies dépendantes de l'activation de ce récepteur. Les nouveaux composés se conforment à la formule structurelle (I). Dans la formule (I), notamment, au moins un parmi les deux substituants R4 est un atome de fluor et au moins un parmi R2 et R3 est un groupe -(CH₂)_n-CONR_aR_b, où R1, R2, R3, R4, n, R_a, R_b sont définis dans la description.