2-甲基-2,4,5,6-四氢环戊烯并[c]吡唑-3-羧酸 | 129560-01-6

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-甲基-2,4,5,6-四氢环戊烯并[c]吡唑-3-羧酸
• 英文名称: 2-methyl-2,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid
• 英文别名: 2-methyl-5,6-dihydro-4H-cyclopenta[c]pyrazole-3-carboxylic acid
• CAS: 129560-01-6
• 化学式: C₈H₁₀N₂O₂
• 分子量: 166.18
• InChiKey: YOZQPUMFUSTCFY-UHFFFAOYSA-N

物化性质

• 熔点：
  200.5 °C
• 沸点：
  358.2±42.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

制备方法与用途

应用广泛的2-甲基-2,4,5,6-四氢环戊二烯并[C]吡唑-3-羧酸，可用作有机合成中间体和医药中间体，在实验室研发及医药化工生产中发挥重要作用。

反应信息

• 作为反应物：
  描述：

  2-甲基-2,4,5,6-四氢环戊烯并[c]吡唑-3-羧酸 生成 2-methyl-2,4,5,6-tetrahydro-cyclopentapyrazole
  参考文献：
  名称：

  v. Auwers; Noll, Justus Liebigs Annalen der Chemie, 1938, vol. 536, p. 97,108

  摘要：

  DOI：
• 作为产物：
  描述：

  环戊酮 在 乙醇 、 sodium ethanolate 、 sodium acetate 作用下， 生成 2-甲基-2,4,5,6-四氢环戊烯并[c]吡唑-3-羧酸
  参考文献：
  名称：

  v. Auwers; Noll, Justus Liebigs Annalen der Chemie, 1938, vol. 536, p. 97,108

  摘要：

  DOI：

文献信息

• [EN] SPIROPIPERIDINE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES DE SPIROPIPÉRIDINE DES RÉCEPTEURS NICOTINIQUES DE L'ACÉTYLCHOLINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2019212927A1

  公开（公告）日：2019-11-07

  The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).

  本公开涉及公式I的化合物，这些化合物可用作7 nAChR的调节剂，包含这些化合物的组合物，以及利用这些化合物预防、治疗或改善疾病，特别是中枢神经系统疾病，如阿尔茨海默病、帕金森病和精神分裂症中的认知障碍，以及L-多巴引起的运动障碍和炎症。
• [EN] PYRIDINESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF<br/>[FR] DÉRIVATIFS DE PYRIDINESULFONAMIDE POUVANT ÊTRE UTILISÉS COMME MODULATEURS TRAP1 ET LEURS UTILISATIONS
  申请人：AMATHUS THERAPEUTICS INC

  公开号：WO2021188907A1

  公开（公告）日：2021-09-23

  The present disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor ("TNF") receptor associated protein 1 ("TRAP1") modulators (e.g., TRAP1 activators). The provided compounds may also rescue the activity in PTEN-induced kinase 1 ("PINK1") loss of function contexts. The provided compounds may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds may also refold or solubilize aggregated or misfolded proteins such as a-synuclein. The present disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof).

  本公开提供了化合物的化学式（I）和药学上可接受的盐、溶剂化合物、水合物、多晶型、共晶体、互变异构体、立体异构体、同位素标记化合物以及其前药。所提供的化合物可能是肿瘤坏死因子（"TNF"）受体相关蛋白1（"TRAP1"）调节剂（例如，TRAP1激活剂）。所提供的化合物还可能恢复PTEN诱导的激酶1（"PINK1"）功能丧失情况下的活性。所提供的化合物还可能改善线粒体的健康、功能、质量、数量和/或活性，和/或减少活性氧自由基的产生。所提供的化合物还可能对聚集或错误折叠的蛋白质（如α-突触核蛋白）进行重折叠或溶解。本公开还提供了包括所提供化合物的药物组合物；包括所提供化合物或药物组合物的试剂盒；以及使用所提供的化合物和药物组合物的方法（例如，用于治疗需要的受试者的疾病）。
• Spiropiperidine allosteric modulators of nicotinic acetylcholine receptors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US11332463B2

  公开（公告）日：2022-05-17

  The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).

  本公开涉及可用作 7 nAChR 调节剂的式 I 化合物、包含此类化合物的组合物，以及使用此类化合物预防、治疗或改善疾病，特别是中枢神经系统疾病，如阿尔茨海默病、帕金森病和精神分裂症中的认知障碍，以及 L-DOPA 诱导的运动障碍和炎症 (I)。
• Optimization of Novel 1-Methyl-1<i>H</i>-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber’s Pole Worm
  作者：Thuy G. Le、Abhijit Kundu、Atanu Ghoshal、Nghi H. Nguyen、Sarah Preston、Yaqing Jiao、Banfeng Ruan、Lian Xue、Fei Huang、Jennifer Keiser、Andreas Hofmann、Bill C. H. Chang、Jose Garcia-Bustos、Abdul Jabbar、Timothy N. C. Wells、Michael J. Palmer、Robin B. Gasser、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.8b01544

  日期：2018.12.13

  A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 mu M. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 mu M. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 mu M.
• SPIROPIPERIDINE ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3788043A1

  公开（公告）日：2021-03-10