{3-[3-(cyclopentyloxy)-4-methoxyphenyl]-4,5-dihydroisoxazol-5-yl}acetic acid | 167099-15-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: {3-[3-(cyclopentyloxy)-4-methoxyphenyl]-4,5-dihydroisoxazol-5-yl}acetic acid
• 英文别名: 3-(3-Cyclopentyloxy-4-methoxy)phenyl-2-isoxazoline-5-acetic Acid；2-[3-(3-Cyclopentyloxy-4-methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetic acid
• CAS: 167099-15-2
• 化学式: C₁₇H₂₁NO₅
• 分子量: 319.357
• InChiKey: OAKYIUBRIRUDHP-UHFFFAOYSA-N

物化性质

• 熔点：
  126-128 °C
• 沸点：
  498.6±55.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  77.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {3-[3-(cyclopentyloxy)-4-methoxyphenyl]-4,5-dihydroisoxazol-5-yl}acetic acid 在 盐酸 、 sodium hydroxide 、 盐酸羟胺 作用下， 生成 2-[3-(3-cyclopentyloxy-4-methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]-N-hydroxyacetamide
  参考文献：
  名称：

  异羟肟酸取代对两个系列咯利普兰类似物的磷酸二酯酶4型（PDE4）和TNFα抑制活性的显着影响：对PDE4新活性位点模型的影响。

  摘要：

  DOI：

  10.1021/jm970685m
• 作为产物：
  描述：

  3-(cyclopentyloxy)-4-methoxybenzaldehyde oxime 在 N-氯代丁二酰亚胺 、 三乙胺 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.5h， 生成 {3-[3-(cyclopentyloxy)-4-methoxyphenyl]-4,5-dihydroisoxazol-5-yl}acetic acid
  参考文献：
  名称：

  [EN] NEW COMPOUNDS HAVING A SELECTIVE PDE4D INHIBITING ACTIVITY
  [FR] NOUVEAUX COMPOSÉS PRÉSENTANT UNE ACTIVITÉ D'INHIBITION SÉLECTIVE VIS-À-VIS DE PDE4D

  摘要：

  化合物的化学式（I），其中Z = 环戊基，环丙甲基，-CH3；R' = -CH3，CHF2，X = 化学式（II）（III）（IV）（V），Y = -CO；-C=O（CH2），-CH（OH）-CH2，-CH2-C=O，-CH2-CH2-C=O；-CH2-CH（OH）-CH2，-CH2-CH（OCOR1）-CH2，NR2 = -N（CH2-CH2OH）2，化学式（VI）（VII）（VIII）（IX）（X）（XI），R1 = 可选择地取代的C1-C8烷基，可选择地取代的芳基；可选择地取代的芳基烷基，优选C1-C3烷基，更优选CH3；以及其对映体，异构体和药学上可接受的盐；这些化合物具有PDE4D抑制活性，可用作治疗痴呆症，特别是阿尔茨海默病，并改善记忆的药物。

  公开号：

  WO2015121212A1

文献信息

• New compounds as selective PDE4D inhibitors
  申请人：UNIVERSITA DEGLI STUDI DI GENOVA

  公开号：EP2907806A1

  公开（公告）日：2015-08-19

  Compounds of formula (I), wherein Z = cyclopentyl, cyclopropylmethyl, -CH3; R' = -CH3, CHF2, X= Y = -CO; -C=O(CH2), -CH(OH)-CH2, -CH2-C=O, -CH2-CH2-C=O; -CH2-CH(OH)-CH2, -CH2-CH(OCOR1)-CH2; NR2 = -N(CH2-CH2OH)2, R1 = optionally substituted C1-C8 alkyl, optionally substituted aryl; optionally substituted aralkyl, preferably C1-C3 alkyl, more preferably CH3; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof. These compounds have a PDE4D inhibiting activity and can be used as a medicament for treating dementia, in particular Alzheimer disease, and for improving memory.

  式(I)化合物、 其中 Z = 环戊基、环丙基甲基、-CH3； R' = -CH3、CHF2、 X= y = -co；-c=o(ch2)，-ch(oh)-ch2，-ch2-c=o，-ch2-ch2-c=o；-ch2-ch(oh)-ch2，-ch2-ch(ocor1)-ch2； NR2 = -N（CH2-CH2OH）2、 R1 = 任选取代的 C1-C8 烷基，任选取代的芳基；任选取代的芳烷基，优选 C1-C3 烷基，更优选 CH3； 及其对映体、非对映异构体和药学上可接受的盐。 这些化合物具有 PDE4D 抑制活性，可用作治疗痴呆症（尤其是阿尔茨海默病）和改善记忆的药物。
• Compounds having a selective PDE4D inhibiting activity
  申请人：UNIVERSITÂ DEGLI STUDI DI GENOVA

  公开号：US10017480B2

  公开（公告）日：2018-07-10

  Compounds of formula (I), wherein Z=cyclopentyl. cyclopropylmethyl, —CH3; R′═—CH3, CHF2, X=formula (II) (III) (IV) (V) Y=—CO; —C═O(CH2), —CH(OH)—CH2, —CH2—C═O, —CH2—CH2—C═O; —CH2—CH(OH)—CH2, —CH2—CH(OCOR1)—CH2 NR2═ —N(CH2—CH2OH)2, formula (VI) (VII) (VIII) (IX) (X) (XI) R1=optionally substituted C1-C8 alkyl, optionally substituted aryl; optionally substituted aralkyl, preferably C1-C3 alkyl, more preferably CH3; and enantiomers, diastereoisomers and pharmaceutically acceptable salts thereof; these compounds have a PDE4D inhibiting activity and can be used as a medicament for treating dementia, in particular Alzheimer disease, and for improving memory.

  式 (I) 的化合物，其中 Z= 环戊基。环丙基甲基，-CH3；R′═-CH3，CHF2，X=式(II) (III) (IV) (V) Y=-CO；-C═O(CH2)，-CH(OH)-CH2，-CH2-C═O，-CH2-CH2-C═O；-CH2-CH(OH)-CH2，-CH2-CH(OCOR1)-CH2 NR2═ -N(CH2-CH2OH)2，式(VI) (VII) (VIII) (IX) (X) (XI) R1=任选取代的 C1-C8 烷基，任选取代的芳基；任选取代的芳烷基，优选 C1-C3 烷基，更优选 CH3；及其对映体、非对映异构体和药学上可接受的盐；这些化合物具有 PDE4D 抑制活性，可用作治疗痴呆症，特别是阿尔茨海默病和改善记忆的药物。
• Isoxazoline compounds having MIF antagonist activity
  申请人：——

  公开号：US20030008908A1

  公开（公告）日：2003-01-09

  Methods of use and pharmaceutical compositions for a genus of low molecular weight compounds comprising optionally substituted isoxazoline ring systems that act as inhibitors of MIF (macrophage migration inhibitory factor) are disclosed. Specifically, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

  本发明公开了一种低分子量化合物的使用方法和药物组合物，该化合物包含可选取代的异噁唑啉环系统，可作为 MIF（巨噬细胞迁移抑制因子）的抑制剂。具体来说，这些化合物可用于治疗多种涉及炎症活动或促炎细胞因子反应的疾病，如自身免疫性疾病（包括风湿性关节炎、胰岛素依赖型糖尿病、多发性硬化症、移植物抗宿主病、狼疮综合征）、慢性肾脏病、糖尿病、高血压、高血脂、高血糖等、狼疮综合征）、哮喘、关节炎、ARDS、银屑病、白细胞介素-2毒性、增生性血管疾病、各种形式的败血症和脓毒性休克，以及其他以潜在的 MIF 反应为特征的疾病，包括肿瘤生长和血管新生（血管生成）等。
• Compounds, compositions, processes of making, and methods of use related to inhibiting macrophage migration inhibitory factor
  申请人：Sielecki-Dzurdz Thais

  公开号：US20050250826A1

  公开（公告）日：2005-11-10

  The present invention provides a compound having Formula I or II: wherein B, R, X, Ar, and Y are defined herein, pharmaceutically acceptable salts thereof and pharmaceutically acceptable prodrugs thereof. The present invention also provides methods of making and using the compound.

  本发明提供了具有式 I 或式 II 的化合物： 其中 B、R、X、Ar 和 Y 在此定义的化合物、其药学上可接受的盐及其药学上可接受的原药。本发明还提供了制造和使用该化合物的方法。
• New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment
  作者：Chiara Brullo、Roberta Ricciarelli、Jos Prickaerts、Ottavio Arancio、Matteo Massa、Chiara Rotolo、Alessia Romussi、Claudia Rebosio、Barbara Marengo、Maria Adelaide Pronzato、Britt T.J. van Hagen、Nick P. van Goethem、Pasqualina D'Ursi、Alessandro Orro、Luciano Milanesi、Sara Guariento、Elena Cichero、Paola Fossa、Ernesto Fedele、Olga Bruno

  DOI：10.1016/j.ejmech.2016.08.018

  日期：2016.11

  Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development. (C) 2016 Elsevier Masson SAS. All rights reserved.