diethyl hydroxy<2-oxo-2-(4-pyridinyl)ethyl>propanedioate | 80843-41-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: diethyl hydroxy<2-oxo-2-(4-pyridinyl)ethyl>propanedioate
• 英文别名: diethyl hydroxy[2-oxo-2-(4-pyridinyl)ethyl]propanedioate；diethyl 2-hydroxy-2-(2-oxo-2-pyridin-4-ylethyl)propanedioate
• CAS: 80843-41-0
• 化学式: C₁₄H₁₇NO₆
• 分子量: 295.292
• InChiKey: KZBNMPJVBPMBCG-UHFFFAOYSA-N

物化性质

• 熔点：
  130-132 °C(Solv: ethanol (64-17-5))
• 沸点：
  463.3±45.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl hydroxy<2-oxo-2-(4-pyridinyl)ethyl>propanedioate 在 盐酸肼 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 23.5h， 生成 2,3-dihydro-3-oxo-6-(4-pyridinyl)-4-pyridazinecarboxylic acid hydrazide
  参考文献：
  名称：

  Synthesis of Aza Analogs of Amrinone

  摘要：

  The aldol condensation product (4) of 4-acetylpyridine (2) and diethyl mesoxalate (3) was converted to pyridazinecarboxylic acid hydrazide (6). Curtius reaction of 6 gave aminopyridazinone (7). The condensation of (4-pyridinyl)glyoxal (17) with aminomalonamide (9) yielded pyrazinecarboxamide (18) which was transformed to aminopyrazinone (19) by the Hofmann reaction. Curtius reaction of 1,2,4-triazinone-5-carboxylic acid (21b) gave aminotriazinone (22). Demethylation of methoxypyrimidine (29) prepared from methyl 2-methoxyformylacetate (25) and isonicotinamidine (26) gave pyrimidinol (30).

  DOI：

  10.3987/com-90-5562
• 作为产物：
  描述：

  4-乙酰吡啶 、 酮基丙二酸二乙酯 在 氮气 作用下， 反应 15.0h， 以to provide diethyl 2-hydroxy-2-(4-pyridyl)cabonylmethyl-malonate as a crystalline solid的产率得到diethyl hydroxy<2-oxo-2-(4-pyridinyl)ethyl>propanedioate
  参考文献：
  名称：

  Pyridazines as interleukin-1.beta. converting enzyme inhibitors

  摘要：

  本发明公开了式（I）的化合物及其药学上可接受的盐：##STR1## 其中R.sub.1是卤素或氧链离去基，包括芳香醚，烷基磺酸盐，芳基磺酸盐，烷基膦酸盐，芳基膦酸盐，烷基磷酸盐或芳基磷酸盐; R.sub.2是COOR.sub.5，C(.dbd.O)NH(CHR.sub.5).sub.m --COOR.sub.5，NH(CHR.sub.5).sub.m CON(R.sub.5)R.sub.6，C(.dbd.O)N(R.sub.5)R.sub.6或NH(CHR.sub.5).sub.m OH; R.sub.3是H或烷基; R.sub.4是H，取代或未取代的芳基，杂芳基或烷基; R.sub.5和R.sub.6独立地是H，低烷基，芳基，羟基烷基，氨基烷基，杂芳基，低烷基烯基芳基，低烷基烯基杂芳基或低环烷基; m=0-6; 包含该化合物的药物组合物; 以及利用该化合物和组合物抑制哺乳动物中白细胞介素-1β蛋白酶活性的方法。

  公开号：

  US06121266A1

文献信息

• 4-Substituted-6-(pyridinyl)-3(2h)-pyridazinones and their use as
  申请人：Sterling Drug Inc.

  公开号：US04304776A1

  公开（公告）日：1981-12-08

  2-R-4-R'-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as intermediates and some as cardiotonics, are prepared by reacting di-(lower-alkyl) hydroxy[2-oxo-2-PY-ethyl]propanedioate (II) with a hydrazine salt of the formula RNHNH.sub.2.nH.sub.x An (III) to produce lower-alkyl 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylate (Ia where R' is lower-carbalkoxy) and reacting Ia with hydrazine hydrate or anhydrous hydrazine to produce 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (Ib where R' is aminocarbamyl), where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl, R' is carbamyl, carboxy, aminocarbamyl or lower-carbalkoxy, n is 1 or 2, x is 1, 2 or 3, and An is an anion of a strong inorganic acid or an organic sulfonic acid. Also shown are: the preparation of II from PY--COCH.sub.3 (IV), the conversion of Ia to Ib (Id where R' is carboxy), and the use of 2-R-4-R"-6-PY-3(2H)-pyridazinones (I where R is lower-alkyl or lower-hydroxyalkyl and R" is carbamyl, aminocarbamyl or lower-carbalkoxy) as cardiotonic agents. Other intermediates are shown.

  2-R-4-R'-6-PY-3(2H)-吡啶并咪唑酮（I）或其盐，可作为中间体和一些作为心脏强心剂，通过将二（较低烷基）羟基[2-氧代-2-PY-乙基]丙二酸酯（II）与公式RNHNH.sub.2.nH.sub.x An（III）的肼盐反应制备，以产生较低烷基2,3-二氢-2-R-3-氧代-6-PY-4-吡啶并咪唑羧酸酯（Ia，其中R'为较低碳烷氧基），并将Ia与肼水合物或无水肼反应，以产生2,3-二氢-2-R-3-氧代-6-PY-4-吡啶并咪唑羧酸肼（Ib，其中R'为氨基羰基），其中PY为4-或3-吡啶基或带有一个或两个较低烷基取代基的4-或3-吡啶基，R为氢、较低烷基或较低羟基烷基，R'为羰基、羧基、氨基羰基或较低碳烷氧基，n为1或2，x为1、2或3，An为强无机酸或有机磺酸的阴离子。还显示了：从PY--COCH.sub.3（IV）制备II，将Ia转化为Ib（其中R'为羧基），以及将2-R-4-R"-6-PY-3(2H)-吡啶并咪唑酮（I，其中R为较低烷基或较低羟基烷基，R"为羰基、氨基羰基或较低碳烷氧基）用作心脏强心剂。还显示了其他中间体。
• 4-Amino-6-(pyridinyl)-3(2H)-pyridazinones and their use as cardiotonics
  申请人：Sterling Drug Inc.

  公开号：US04305943A1

  公开（公告）日：1981-12-15

  4-Amino-2-R-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as cardiotonics, where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents are prepared by: (a) reaction of 2-R-6-PY-3(2H)-pyridazinone (II) with hydrazine; (b) conversion from 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxamide (III); or, (c) conversion form 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (IV). Also shown are: the use of I or salts as cardiotonic agents; and, the preparation of intermediates.

  4-氨基-2-R-6-PY-3(2H)-吡啶并嗪酮(I)或其盐，可用作心力衰竭药物，其中R为氢、低烷基或低羟基烷基，PY为4-或3-吡啶基或带有一个或两个低烷基取代基的4-或3-吡啶基，通过以下方法制备：(a) 2-R-6-PY-3(2H)-吡啶并嗪酮(II)与肼的反应；(b) 从2,3-二氢-2-R-3-氧代-6-PY-4-吡啶并嗪甲酰胺(III)转化而来；或(c) 从2,3-二氢-2-R-3-氧代-6-PY-4-吡啶并嗪羧酸肼酰肼(IV)转化而来。还显示了：将I或其盐用作心力衰竭药物；以及中间体的制备。
• Pyridazines as interleukin-1beta converting enzyme inhibitors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20040110725A1

  公开（公告）日：2004-06-10

  Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: 1 wherein R 1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate; R 2 is COOR 5 , C(═O)NH(CHR 5 ) m —COOR 5 , NH(CHR 5 ) m CON(R 5 )R 6 , C(═O)N(R 5 )R 6 or NH(CHR 5 ) m OH; R 3 is H or alkyl; R 4 is H, sybstituted or unsubstituted aryl, heteroaryl or alkyl; R 5 and R 6 are independently H, lower alkyl, aryl, hydroxy alkyl, amino alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycloalkyl; and m=0-6; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1&bgr; protease activity in a mammal utilizing the compounds and compositions.

  本发明涉及式(I)的化合物及其药学上可接受的盐：1其中R1是卤素或含芳香醚、烷基磺酸酯、芳基磺酸酯、烷基膦酸酯、芳基膦酸酯、烷基磷酸酯或芳基磷酸酯的氧链离去基；R2是COOR5、C(═O)NH(CHR5)m—COOR5、NH(CHR5)mCON(R5)R6、C(═O)N(R5)R6或NH(CHR5)mOH；R3是氢或烷基；R4是氢、取代或未取代的芳基、杂芳基或烷基；R5和R6独立地是氢、低烷基、芳基、羟基烷基、氨基烷基、杂芳基、低烷基-芳基、低烷基-杂芳基或低环烷基；m=0-6；含有这些化合物的药物组合物；以及利用这些化合物和组合物抑制哺乳动物中白细胞介素-1β蛋白酶活性的方法。
• Preparation of 4-amino-6-(pyridinyl)-3(2H)-pyridazinones from
  申请人：Sterling Drug Inc.

  公开号：US04346221A1

  公开（公告）日：1982-08-24

  4-Amino-2-R-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as cardiotonics, where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents are prepared by: (a) reaction of 2-R-6-PY-3(2H)-pyridazinone (II) with hydrazine; (b) conversion from 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxamide (III); or, (c) conversion form 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (IV). Also shown are: the use of I or salts as cardiotonic agents; and, the preparation of intermediates.

  4-氨基-2-R-6-PY-3（2H）-吡啶嗪酮（I）或其盐，可用作心脏强心剂，其中R为氢，低烷基或低羟基烷基，PY为4-或3-吡啶基或带有一个或两个低烷基取代基的4-或3-吡啶基，通过以下方法制备：（a）2-R-6-PY-3（2H）-吡啶嗪酮（II）与肼反应；（b）由2,3-二氢-2-R-3-氧代-6-PY-4-吡啶嗪羧酰胺（III）转化而来；或（c）由2,3-二氢-2-R-3-氧代-6-PY-4-吡啶嗪羧酸肼（IV）转化而来。还显示了：将I或其盐用作心脏强心剂的用途；以及中间体的制备。
• Pyridazines as interleukin-1.beta. converting enzyme inhibitors
  申请人：Vertex Pharmaceuticals, Inc.

  公开号：US06121266A1

  公开（公告）日：2000-09-19

  Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein R.sub.1 is a halogen, or an oxygen linked leaving group including an aromatic ether, an alkyl sulfonate, an aryl sulfonate, an alkyl phosphonate, an aryl phosphonate, an alkyl phosphate or aryl phosphate; R.sub.2 is COOR.sub.5, C(.dbd.O)NH(CHR.sub.5).sub.m --COOR.sub.5, NH(CHR.sub.5).sub.m CON(R.sub.5)R.sub.6, C(.dbd.O)N(R.sub.5)R.sub.6 or NH(CHR.sub.5).sub.m OH; R.sub.3 is H or alkyl; R.sub.4 is H, substituted or unsubstituted aryl, heteroaryl or alkyl; R.sub.5 and R.sub.6 are independently H, lower alkyl, aryl, hydroxy alkyl, amino alkyl, heteroaryl, lower alkylene-aryl, lower alkylene-heteroaryl or lower cycloalkyl; and m=0-6; pharmaceutical compositions containing the compounds; and a method for inhibiting interleukin-1.beta. protease activity in a mammal utilizing the compounds and compositions.

  本发明公开了式（I）的化合物及其药学上可接受的盐：##STR1## 其中R.sub.1是卤素或氧链离去基，包括芳香醚，烷基磺酸盐，芳基磺酸盐，烷基膦酸盐，芳基膦酸盐，烷基磷酸盐或芳基磷酸盐; R.sub.2是COOR.sub.5，C(.dbd.O)NH(CHR.sub.5).sub.m --COOR.sub.5，NH(CHR.sub.5).sub.m CON(R.sub.5)R.sub.6，C(.dbd.O)N(R.sub.5)R.sub.6或NH(CHR.sub.5).sub.m OH; R.sub.3是H或烷基; R.sub.4是H，取代或未取代的芳基，杂芳基或烷基; R.sub.5和R.sub.6独立地是H，低烷基，芳基，羟基烷基，氨基烷基，杂芳基，低烷基烯基芳基，低烷基烯基杂芳基或低环烷基; m=0-6; 包含该化合物的药物组合物; 以及利用该化合物和组合物抑制哺乳动物中白细胞介素-1β蛋白酶活性的方法。