(4-cyano-3-fluoro-phenyl)-acetic acid ethyl ester | 444807-48-1

• 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: (4-cyano-3-fluoro-phenyl)-acetic acid ethyl ester
• 英文别名: Ethyl 4-cyano-3-fluorophenylacetate；ethyl 2-(4-cyano-3-fluorophenyl)acetate
• CAS: 444807-48-1
• 化学式: C₁₁H₁₀FNO₂
• 分子量: 207.204
• InChiKey: GCGYPUSSBVJWGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-cyano-3-fluoro-phenyl)-acetic acid ethyl ester 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 (4-aminomethyl-3-fluoro-phenyl)acetic acid ethyl ester
  参考文献：
  名称：

  Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes

  摘要：

  公开号：

  EP1229034B1
• 作为产物：
  描述：

  zinc(II) cyanide 、 在 四(三苯基膦)钯 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 4.0h， 生成 (4-cyano-3-fluoro-phenyl)-acetic acid ethyl ester
  参考文献：
  名称：

  Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes

  摘要：

  公开号：

  EP1229034B1

文献信息

• Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes
  申请人：Pfizer Inc.

  公开号：US20020111495A1

  公开（公告）日：2002-08-15

  Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructuive pulmonary disease, of the formula: 1 wherein j is 0 or 1, k is 0 or 1, m is 0, 1, or 2; n is 1 or 2; A is selected from the partial Formulas: 2 where q is 1, 2, or 3, W 3 is —O—; —N(R 9 )—; or —OC(═O)—; R 7 is selected from —H; —(C 1 -C 6 ) alkyl, —(C 2 -C 6 ) alkenyl, or —(C 2 -C 6 ) alkynyl substituted by 0 to 3 substituents R 10 ; —(CH 2 ) u —(C 3 -C 7 ) cycloalkyl where u is 0, 1 or 2, substituted by 0 to 3 R 10 ; and phenyl or benzyl substituted by 0 to 3 R 14 ; R 8 is tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-on-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-on-3-yl; 1,2,4-oxadiazol-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinyl; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onyl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; indolyl; indolinyl; isoindolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazolo[3,4-d]pyrimidinyl; pyrimido[4,5-d]pyrimidinyl; imidazo[1,2-a]pyridinyl; pyridopyridinyl; pteridinyl; or 1H-purinyl; or A is selected from phosphorous and sulfur acid groups; W is —O—; —S(═O) t —, where t is 0, 1, or 2; or —N(R 3 )—; Y is ═C(R 1 a )—, or —[N (O) k ] where k is 0 or 1; R 4 , R 5 and R 6 are (1) —H; provided that R 5 and R 6 are not both —H at the same time, —F; —Cl; —(C 2 -C 4 ) alkynyl; —R 16 ; —OR 16 ; —S(═O) p R 16 ; —C(═O)R 16 , —C(═O)OR 16 , —C(═O)OR 16 ; —OC(═O)R 16 ; —CN; —NO 2 ; —C(═O)NR 16 R 17 ; —OC(═O)NR 16 R 17 ; —NR 12 a C(═O)NR 16 R 17 ; —NR 12 a C(═NR 12 )NR 16 R 17 ; —NR 12 a C(═NCN)NR 16 R 16 ; —NR 12 a C(═N—NO 2 )NR 15 R 16 ; —C(═NR 12 a )NR 15 R 16 ; —CH 2 C(═NR 12 a )NR 16 R 17 ; —OC(═NR 12 a )NR 16 R 17 ; —OC(═N—NO 2 )NR 16 R 17 ; —NR 16 R 17 ; —CH 2 NR 16 R 17 ; —NR 12 a C(═O)R 16 ; —NR 12 a C(═O)OR 16 ; ═NOR 16 ; —NR 12 a S(═O) p R 17 —S(═O) p NR 16 R 17 ; and —CH 2 C(═NR 12 a )NR 16 R 17 ; (2) —(C 1 -C 4 ) alkyl including dimethyl and —(C 1 -C 4 ) alkoxy substituted with 0 to 3 substituents —F or —Cl; or 0 or 1 substituent (C 1 -C 2 ) alkoxycarbonyl-, (C 1 -C 2 ) alkylcarbonyl-, or (C 1 -C 2 ) alkylcarbonyloxy-; or (3) an aryl or heterocyclic moiety; or (4) R 5 and R 6 are taken together to form a moiety of partial Formulas (1.3.1) through (1.3.15): 3 or a pharmaceutically acceptable salt thereof.

  本发明涉及一种化合物，其在治疗由嗜酸性粒细胞活化和脱颗粒调节的疾病中，特别是哮喘、慢性支气管炎和慢性阻塞性肺疾病中作为PDE4抑制剂有用，其化学式为：其中j为0或1，k为0或1，m为0、1或2；n为1或2；A从部分式中选取：其中q为1、2或3，W3为—O—；—N(R9)—；或—OC(═O)—；R7选自—H；—(C1-C6)烷基、—(C2-C6)烯基或—(C2-C6)炔基，其上可有0至3个取代基R10；—(CH2)u—(C3-C7)环烷基，其中u为0、1或2，其上可有0至3个取代基R10；以及苯基或苄基，其上可有0至3个取代基R14；R8为四唑-5-基；1,2,4-三唑-3-基；1,2,4-三唑-3-酮-5-基；1,2,3-三唑-5-基；咪唑-2-基；咪唑-4-基；咪唑啉-2-酮-4-基；1,3,4-噁二唑基；1,3,4-噁二唑-2-酮-5-基；1,2,4-噁二唑-3-基；1,2,4-噁二唑-5-酮-3-基；1,2,4-噁二唑-5-基；1,2,4-噁二唑-3-酮-5-基；1,2,5-噻二唑基；1,3,4-噻二唑基；吗啉基；对噻嗪基；噁唑基；异噁唑基；噻唑基；异噻唑基；吡咯基；吡唑基；琥珀酰亚胺基；戊二酰亚胺基；吡咯烷基；2-哌啶酮基；2-吡啶酮基；4-吡啶酮基；吡啶嗪-3-酮基；吡啶基；嘧啶基；吡嗪基；吡啶嗪基；吲哚基；吲哚啉基；异吲哚啉基；苯并[b]呋喃基；2,3-二氢苯并呋喃基；1,3-二氢异苯并呋喃基；2H-1-苯并吡喃基；2-H-香豆素基；香豆素基；苯并噻吩基；1H-吲唑基；苯并咪唑基；苯并噁唑基；苯并异噁唑基；苯并噻唑基；苯并三唑基；苯并三唑啉基；邻苯二酚基；1,8-萘啶基；喹啉基；异喹啉基；喹唑啉基；喹啉酮基；吡唑并[3,4-d]嘧啶基；嘧啶并[4,5-d]嘧啶基；咪唑并[1,2-a]吡啶基；吡啶吡啶基；噻吩基；或1H-嘌呤基；或A选自磷和硫酸基；W为—O—；—S(═O)t—，其中t为0、1或2；或—N(R3)—；Y为═C(R1a)—，或—[N(O)k]，其中k为0或1；R4、R5和R6为(1) —H；但是当R5和R6同时不为—H时，可以为—F；—Cl；—(C2-C4)炔基；—R16；—OR16；—S(═O)pR16；—C(═O)R16、—C(═O)OR16、—C(═O)OR16；—OC(═O)R16；—CN；—NO2；—C(═O)NR16R17；—OC(═O)NR16R17；—NR12aC(═O)NR16R17；—NR12aC(═NR12)NR16R17；—NR12aC(═NCN)NR16R16；—NR12aC(═N—NO2)NR15R16；—C(═NR12a)NR15R16；—CH2C(═NR12a)NR16R17；—OC(═NR12a)NR16R17；—OC(═N—NO2)NR16R17；—NR16R17；—CH2NR16R17；—NR12aC(═O)R16；—NR12aC(═O)OR16；═NOR16；—NR12aS(═O)pR17—S(═O)pNR16R17；和—CH2C(═NR12a)NR16R17；(2) —(C1-C4)烷基，包括二甲基和—(C1-C4)烷氧基，其上可有0至3个取代基—F或—Cl；或者0或1个取代基(C1-C2)烷氧羰基、(C1-C2)烷基羰基或(C1-C2)烷基羰氧基；或者(3) 芳基或杂环基；或者(4) R5和R6聚合形成部分式(1.3.1)到(1.3.15)中的一个基团；或其药学上可接受的盐。
• US7250518B2
  申请人：——

  公开号：US7250518B2

  公开（公告）日：2007-07-31
• Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes
  申请人：Pfizer Products Inc.

  公开号：EP1229034B1

  公开（公告）日：2005-04-13