1-cyclopentyl-3-ethyl-6(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1-H-pyrazolo[3,4-c]pyridine | 162141-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-cyclopentyl-3-ethyl-6(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1-H-pyrazolo[3,4-c]pyridine
• 英文别名: 1-cyclopentyl-3-ethyl-6-(4-methoxyphenyl)-4,5-dihydropyrazolo[3,4-c]pyridin-7-one
• CAS: 162141-77-7
• 化学式: C₂₀H₂₅N₃O₂
• 分子量: 339.437
• InChiKey: VLJHFRUUVXVJPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-cyclopentyl-3-ethyl-6(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1-H-pyrazolo[3,4-c]pyridine 在 ammonium cerium (IV) nitrate 、 tetraphosphorus decasulfide 、 水 作用下， 以 1,4-二氧六环 、 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
• 作为产物：
  描述：

  γ-己内酯 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 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 、 乙醇 、 二氯甲烷 为溶剂， 生成 1-cyclopentyl-3-ethyl-6(4-methoxyphenyl)-7-oxo-4,5,6,7-tetrahydro-1-H-pyrazolo[3,4-c]pyridine
  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] BICYCLIC TETRAHYDRO PYRAZOLOPYRIDINES<br/>[FR] TETRAHYDRO PYRAZOLOPYRIDINES BICYCLIQUES
  申请人：PFIZER INC.

  公开号：WO1995001980A1

  公开（公告）日：1995-01-19

  (EN) Compounds of formula (I) wherein R1, R2, R3 and X are as defined. The compounds 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, AIDS, septic shock and other diseases involving the production of TNF.(FR) Composés de la formule (I) dans laquelle R1, R2, R3 et X sont tels que définis dans le descriptif. Les composés de la formule (I) et leurs sels pharmaceutiquement acceptables conviennent à l'inhibition de la phosphodiestérase (PDE) de type IV et de la production du facteur de nécrose tumorale (TNF), ainsi qu'au traitement de l'asthme, de l'arthrite, de la bronchite, des affections chroniques et obstructives des voies aériennes, du psoriasis de la rhinite allergique, de la dermatite et d'autres maladies inflammatoires, du SIDA, du choc septique et d'autres maladies impliquant la production de TNF.

  化合物的化学式为(I)，其中R1、R2、R3和X的定义如所述。化合物(I)和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，并在哮喘、关节炎、支气管炎、慢性阻塞性肺病、银屑病、过敏性鼻炎、皮炎和其他炎症性疾病、艾滋病、脓毒症休克和其他涉及TNF产生的疾病的治疗中有用。
• [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。
• 7-Oxo-4,5,6,7-tetrahydro-1<i>H</i>-pyrazolo[3,4-<i>c</i>]pyridines as Novel Inhibitors of Human Eosinophil Phosphodiesterase
  作者：Allen J. Duplantier、Catharine J. Andresen、John B. Cheng、Victoria L. Cohan、Christian Decker、Frank M. DiCapua、Kenneth G. Kraus、Kerry L. Johnson、Claudia R. Turner、John P. UmLand、John W. Watson、Ronald T. Wester、Alison S. Williams、John A. Williams

  DOI：10.1021/jm9800090

  日期：1998.6.1

  High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent than 11 with IC50 values of 0.03-1.6 mu M. One such compound, CP-220,629 (22) (IC50 = 0.44 mu M), was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 2.0 mg/kg, po) and demonstrated a significant reduction in eosinophil (55%), neutrophil (65%), and IL-1 beta (82%) responses to antigen challenge in atopic monkeys (10 mg/kg, po).
• US06004974
  申请人：——

  公开号：——

  公开（公告）日：——
• BICYCLIC TETRAHYDRO PYRAZOLOPYRIDINES
  申请人：PFIZER INC.

  公开号：EP0707585A1

  公开（公告）日：1996-04-24