7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢- | 185954-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢-
• 英文名称: 1-cyclopentyl-3-ethyl-7-thio-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine
• 英文别名: 1-cyclopentyl-3-ethyl-5,6-dihydro-4H-pyrazolo[3,4-c]pyridine-7-thione
• CAS: 185954-45-4
• 化学式: C₁₃H₁₉N₃S
• 分子量: 249.38
• InChiKey: CMGBZVIPKLLJOG-UHFFFAOYSA-N

物化性质

• 熔点：
  152-153 °C
• 沸点：
  413.3±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢- 在 吡啶 、 silica gel 作用下， 以 乙醚 为溶剂， 反应 9.0h， 生成 5-Benzyl-12-cyclopentyl-10-ethyl-3,4,6,11,12-pentazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,10-tetraene
  参考文献：
  名称：

  SAR of a Series of 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridines as Potent Inhibitors of Human Eosinophil Phosphodiesterase

  摘要：

  The potency and physical properties of a previously reported 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine series of human eosinophil phosphodiesterase inhibitors were improved by tying the lactam moiety into a triazolo ring. The resulting 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine series provided nonionizable analogs with melting point properties suitable for micronization. Substitution at the 3-position of the 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine tricycle led to a 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/mL.

  DOI：

  10.1021/jm060904g
• 作为产物：
  描述：

  γ-己内酯 在 sodium hypochlorite 、 ammonium cerium (IV) nitrate 、 tetraphosphorus decasulfide 、 2,2,6,6-四甲基哌啶氧化物 、 水 、 sodium ethanolate 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 7H-吡唑并[3,4-c]吡啶-7-硫酮,1-环戊基-3-乙基-1,4,5,6-四氢-
  参考文献：
  名称：

  Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine PDE-IV Inhibitor

  摘要：

  An efficient synthesis of the PDE IV inhibitor, 9H.-cyclopentyl.. 7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-,5,6-dihydro-[4,3-a]pyridine I is described. Starting from commercially available gamma -caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4,c]pyridin-7- one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.

  DOI：

  10.1021/op010222x

文献信息

• [EN] TRICYCLIC 5,6-DIHYDRO-9H-PYRAZOLO[3,4-c]-1,2,4-TRIAZOLO[4,3- alpha ]PYRIDINES<br/>[FR] 5,6-DIHYDRO-9H-PYRAZOLO[3,4-c]-1,2-4-TRIAZOLO[4,3- alpha ]PYRIDINES TRICYCLIQUES
  申请人：PFIZER INC.

  公开号：WO1996039408A1

  公开（公告）日：1996-12-12

  (EN) A compound of formula (I), wherein R1, R2, R3, R9 and R10 are as defined in the description. The compound of formula (I) and the pharmaceutically acceptable salts thereof are useful in inhibiting phosphodiesterase (PDE) Type IV and the production of tumor necrosis factor (TNF) and in the treatment of asthma, arthritis, bronchitis, chronic obstructive airways disease, psoriasis, allergic rhinitis, dermatitis and other inflammatory diseases characterized by phosphodiesterase (PDE) Type IV activity as well as AIDS, sepsis, septic shock and other diseases, such as cachexia, involving the production of TNF.(FR) L'invention concerne un composé de la formule (I) dans laquelle R1, R2, R3, R9 et R10 ont la signification donnée dans la description. Ledit composé et ses sels pharmaceutiquement acceptables peuvent être utilisés pour inhiber la phosphodiestérase (PDE) de type IV et la production du facteur de nécrose tumorale (TNF) et pour traiter l'asthme, l'arthrite, la bronchite, une maladie obstructive chronique des voies aériennes supérieures, le psoriasis, la rhinite allergique, la dermatite et d'autres maladies inflammatoires caractérisées par l'activité de la phosphodiestérase (PDE) de type IV, ainsi que le SIDA, la septicémie, un choc septique et d'autres maladies, telles que la cachéxie, impliquant la production du facteur de nécrose tumorale.

  一种化合物的公式(I)，其中R1、R2、R3、R9和R10如描述中所定义。公式(I)化合物及其药学上可接受的盐在抑制磷酸二酯酶(PDE) IV型和肿瘤坏死因子(TNF)的产生方面有用，并用于治疗哮喘、关节炎、支气管炎、慢性阻塞性呼吸道疾病、牛皮癣、过敏性鼻炎、皮炎和其他以磷酸二酯酶(PDE) IV型活性为特征的炎症性疾病，以及艾滋病、败血症、感染性休克和其他涉及TNF产生的疾病，如消耗症。
• TRICYCLIC 5,6-DIHYDRO-9H-PYRAZOLO(3,4-c]-1,2,4-TRIAZOLO(4,3-ALPHA]PYRIDINES
  申请人：PFIZER INC.

  公开号：EP0837860B1

  公开（公告）日：2002-03-20
• TRICYCLIC 5,6-DIHYDRO-9H-PYRAZOLO 3,4-c]-1,2,4-TRIAZOLO 4,3-$g(a)]PYRIDINES
  申请人：PFIZER INC.

  公开号：EP0837860A1

  公开（公告）日：1998-04-29
• US6004974A
  申请人：——

  公开号：US6004974A

  公开（公告）日：1999-12-21