3-methoxy-2-oxo-1-phenyl-4-propionyl-1,2,5,6-tetrahydropyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-methoxy-2-oxo-1-phenyl-4-propionyl-1,2,5,6-tetrahydropyridine
• 英文别名: 4-propanoyl-3-methoxy-1-phenyl-2-oxo-1,2,5,6-tetrahydropyridine；5-Methoxy-1-phenyl-4-propanoyl-2,3-dihydropyridin-6-one
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: NTZBTWWDUGWXNQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-苯基-2-吡咯烷酮 在 sodium hydroxide 、 sodium methylate 作用下， 以 甲醇 、 乙醚 、 乙醇 、 1,2-二氯乙烷 、 苯 为溶剂， 反应 5.75h， 生成 3-methoxy-2-oxo-1-phenyl-4-propionyl-1,2,5,6-tetrahydropyridine
  参考文献：
  名称：

  7-Oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridines as Novel Inhibitors of Human Eosinophil Phosphodiesterase

  摘要：

  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).

  DOI：

  10.1021/jm9800090

文献信息

• [EN] BICYCLIC TETRAHYDRO PYRAZOLOPYRIDINES AND THEIR USE AS MEDICAMENTS<br/>[FR] TETRAHYDROPYRAZOLOPYRIDINES BICYCLIQUES ET LEUR EMPLOI COMME MEDICAMENTS
  申请人：PFIZER INC.

  公开号：WO1996012720A1

  公开（公告）日：1996-05-02

  (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) L'invention concerne des composés de formule (I) où R1, R2, R3 et X sont tels que définis. Les composés de cette formule (I) ainsi que leurs sels acceptables du point de vue pharmaceutique s'avèrent efficaces comme inhibiteurs de la phosphodiestérase (PDE) de type IV et de la production du facteur de nécrose des tumeurs (TNF) ainsi que dans le traitement de l'asthme, de l'arthrite, de la bronchite, des maladies chroniques obstructives des voies respiratoires, du psoriasis, des rhinites allergiques, des dermatites et autres maladies inflammatoires, du syndrome d'immuno-déficience acquise, du choc septique et d'autres affections donnant lieu à une production de TNF.

  化合物的公式（I），其中R1，R2，R3和X如定义。该公式（I）的化合物及其在抑制磷酸二酯酶（PDE）IV型和肿瘤坏死因子（TNF）的产生以及治疗哮喘，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，皮炎和其他炎症性疾病，艾滋病，脓毒症休克和其他涉及TNF产生的疾病中的药物可接受的盐是有用的。
• [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。
• BICYCLIC TETRAHYDRO PYRAZOLOPYRIDINES
  申请人：PFIZER INC.

  公开号：EP0707585A1

  公开（公告）日：1996-04-24
• BICYCLIC TETRAHYDRO PYRAZOLOPYRIDINES AND THEIR USE AS MEDICAMENTS
  申请人：PFIZER INC.

  公开号：EP0787132A1

  公开（公告）日：1997-08-06
• 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).