(Z)-N'-(4-methoxyphenyl)-1-(methylsulfonyl)methanehydrazonoyl chloride | 473927-66-1

• 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: (Z)-N'-(4-methoxyphenyl)-1-(methylsulfonyl)methanehydrazonoyl chloride
• 英文别名: (1Z)-1-[chloro (methylsulfonyl)methylene]-2-(4-methoxyphenyl)hydrazine；(1Z)-N-(4-methoxyphenyl)-1-methylsulfonylmethanehydrazonoyl chloride
• CAS: 473927-66-1
• 化学式: C₉H₁₁ClN₂O₃S
• 分子量: 262.717
• InChiKey: BBHFNIVLNWXMDV-FMIVXFBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-碘苯基)-3-吗啉基-5,6-二氢吡啶-2(1H)-酮 、 (Z)-N'-(4-methoxyphenyl)-1-(methylsulfonyl)methanehydrazonoyl chloride 在 三乙胺 、 盐酸 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以80%的产率得到6-(4-iodophenyl)-1-(4-methoxyphenyl)-3-(methylsulfonyl)-1,4,5,6-tetrahydro-7H-pyrazolo(3,4-c)pyridin-7-one
  参考文献：
  名称：

  Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

  摘要：

  Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P-1 moieties that resulted in the identification of the p-methoxyphenyl P-1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P-4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidinl-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

  DOI：

  10.1021/jm070245n
• 作为产物：
  描述：

  1-chloro-1-(methylsulfonyl)propan-2-one 、 甲氧苯胺 在 盐酸 、 sodium nitrite 、 sodium acetate 作用下， 以 水 、 丙酮 为溶剂， 反应 4.5h， 以57%的产率得到(Z)-N'-(4-methoxyphenyl)-1-(methylsulfonyl)methanehydrazonoyl chloride
  参考文献：
  名称：

  Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

  摘要：

  Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P-1 moieties that resulted in the identification of the p-methoxyphenyl P-1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P-4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidinl-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

  DOI：

  10.1021/jm070245n

文献信息

• Substituted amino methyl factor Xa inhibitors
  申请人：——

  公开号：US20030212054A1

  公开（公告）日：2003-11-13

  The present application describes substituted-aminomethyl substituted compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了替代氨甲基取代化合物及其衍生物，或其药用盐形式，这些化合物可用作因子Xa的抑制剂。
• [EN] 1,1-DISUBSTITUTED CYCLOALKYL DERIVATIVES AS FACTOR XA INHIBITORS<br/>[FR] DERIVES CYCLOALKYLES 1,1-DISUBSTITUES UTILISES EN TANT QU'INHIBITEURS DU FACTEUR XA
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003099276A1

  公开（公告）日：2003-12-04

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物，或其药用可接受的盐形式，这些化合物对于Xa因子的抑制剂具有用处。
• 1,4,5,6-tetrahydropyrazolo-[3,4,-c]-pyridin-7-ones useful as factor Xa inhibitors
  申请人：——

  公开号：US20020177713A1

  公开（公告）日：2002-11-28

  The present application describes 1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-ones of the following formula or pharmaceutically acceptable salt forms thereof: 1 wherein ring R b is 3-amido or 4-methoxy, R a can be cyano, trifluoromethyl, or amido, and R can be a substituted phenyl, a substituted imidazolyl, or a substituted pyridine. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  该申请描述了以下公式或其药学上可接受的盐形式的1,4,5,6-四氢吡唑并-［3,4-c］-吡啶-7-酮：其中环R为3-氨基或4-甲氧基，R可以是氰基、三氟甲基或氨基，R可以是取代苯基、取代咪唑基或取代吡啶基。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，具体来说是因子Xa。
• 1,1-Disubstituted cycloalkyl derivatives as factor Xa inhibitors
  申请人：——

  公开号：US20040254158A1

  公开（公告）日：2004-12-16

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物，或其药学上可接受的盐形式，这些化合物可用作因子Xa的抑制剂。
• 1, 1-disubstituted cycloalkyl derivatives as factor Xa inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US07312214B2

  公开（公告）日：2007-12-25

  The present application describes 1,1-disubstituted cycloalkyl compounds and derivatives thereof, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

  本申请描述了1,1-二取代环烷基化合物及其衍生物或其药学上可接受的盐形式，它们可用作凝血因子Xa的抑制剂。