(+)-cis-6'-chloro-2',3'-dihydro-2'-methyl-spiro-[imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine]-2,5-dione | 126642-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (+)-cis-6'-chloro-2',3'-dihydro-2'-methyl-spiro-[imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine]-2,5-dione
• 英文别名: 2'S,4'R-6'-chloro-2',3'-dihydro-2'-methylspiro(imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine)-2,5-dione；(2S,4R)-6-chloro-2-methylspiro[2,3-dihydropyrano[2,3-b]pyridine-4,5'-imidazolidine]-2',4'-dione
• CAS: 126642-41-9
• 化学式: C₁₁H₁₀ClN₃O₃
• 分子量: 267.672
• InChiKey: WFPFAWQUEPGPQT-ULHQUTTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-cis-6'-chloro-2',3'-dihydro-2'-methyl-spiro-[imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine]-2,5-dione 在 双氧水 、 溶剂黄146 作用下， 以29%的产率得到6'-chloro-2',3'-dihydro-2'-methylspiropyridine>-2,5-dione 8'-oxide
  参考文献：
  名称：

  螺旋乙内酰脲醛糖还原酶抑制剂衍生自8-Aza-4-chromanones。

  摘要：

  制备了一系列衍生自8-氮杂苯并二氢吡喃酮（2,3-二氢-4H-吡喃并[2,3-b]吡啶-4-酮的螺旋乙内酰脲）的醛糖还原酶抑制活性。必须对Bucherer-Bergs标准条件进行彻底修改，以将收率从不到1％提高到可接受的50％范围。最有效的化合物之一是cis-6'-chloro-2'，3'-dihydro-2'-methylspiro [imidazolidine-4,4'-4'H-pyrano [2,3-b] pyridine] -2 ，5-二酮; 该化合物的拆分结果表明2'R，4'S对映异构体16是该系列中活性最高的螺乙内酰脲，对人胎盘醛糖还原酶的IC50为7.5 x 10（-9）。

  DOI：

  10.1021/jm00169a005
• 作为产物：
  描述：

  6-chloro-2,3-dihydro-2-methyl-4H-pyrano<2,3-b>pyridin-4-one 在 ammonium carbonate 、 sodium hydrogensulfite 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 (+)-cis-6'-chloro-2',3'-dihydro-2'-methyl-spiro-[imidazolidine-4,4'-4'H-pyrano[2,3-b]pyridine]-2,5-dione
  参考文献：
  名称：

  Azolidinedione derivatives

  摘要：

  一系列源自2,3-二氢吡喃并[2,3-b]吡啶环系统的新型螺二氮杂环酮已被制备，包括其药学上可接受的盐。这些化合物在治疗上作为醛糖还原酶抑制剂，用于控制某些慢性糖尿病并发症是有用的。典型的成员化合物包括源自上述环系统的螺酰亚胺、螺噁唑烷二酮、螺噻唑烷二酮和螺咪唑烷二酮。(4'S)(2'R)-6'-氯-2',3'-二氢-2'-甲基-螺[咪唑烷-4,4'-4'H-吡喃并[2,3-b]吡啶]-2,5-二酮代表了一个典型且优选的成员化合物。提供了从已知起始原料制备所有这些化合物的方法。

  公开号：

  US04980357A1

文献信息

• Novel triazine compounds useful as sorbitol dehydrogenase inhibitors
  申请人：——

  公开号：US20030004166A1

  公开（公告）日：2003-01-02

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of formula I 1 wherein R 1 , R 2 and R 3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing these compounds which inhibit sorbitol dehydrogenase and to methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy, diabetic cardiomyopathy and foot ulcers, by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of the present invention with a second pharmaceutical agent, including an aldose reductase inhibitor, a sodium hydrogen ion exchange (NHE-1) inhibitor, a glycogen phosphorylase inhibitor (GPI), a selective serotonin reuptake inhibitor, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, an angiotensin converting enzyme inhibitor, a thiazolidinedione antidiabetic agent, an angiotensin 11 receptor antagonist, a &ggr;-aminobutyric acid (GABA) agonist, a phosphodiesterase type 5 inhibitor, an adenosine agonist, and a CETP inhibitor and to methods of using these combination compositions.

  这项发明涉及到化合物的抑制山梨醇脱氢酶的公式I1，其中R1、R2和R3如规范中所定义。这项发明还涉及含有这些化合物的药物组合物，其抑制山梨醇脱氢酶，并通过向患有糖尿病且因此有发生这些并发症风险的哺乳动物施用这些化合物的方法来治疗或预防糖尿病并发症，特别是糖尿病神经病变、糖尿病肾病、糖尿病微血管病、糖尿病大血管病、糖尿病心肌病和足部溃疡。这项发明还涉及含有本发明公式I的化合物与第二药物剂的组合的药物组合物，包括醛糖还原酶抑制剂、钠氢离子交换（NHE-1）抑制剂、糖原磷酸化酶抑制剂（GPI）、选择性5-羟色胺再摄取抑制剂、3-羟基-3-甲基戊二酸辅酶A还原酶抑制剂、血管紧张素转换酶抑制剂、噻唑烷二酮抗糖尿病药物、血管紧张素II受体拮抗剂、γ-氨基丁酸（GABA）激动剂、磷酸二酯酶5抑制剂、腺苷激动剂和CETP抑制剂，以及使用这些组合组合物的方法。
• Fungicidal composition
  申请人：UBE INDUSTRIES, LTD.

  公开号：EP0432894A1

  公开（公告）日：1991-06-19

  Aralkylamine derivatives, preparation thereof and bactericides containing the same Disclosed are a fungicidal composition containing a compound represented by the formula (I): wherein R¹ represents a halogen atom and R² and R³ each represent a lower alkyl group, and R⁴ represents or -CHF₂, or an acid addition salt thereof, and at least one fungicide having ergosterol biosynthesis inhibitive activity or cytokinesis inhibitive activity.

  阿拉基胺衍生物，其制备方法以及含有该物质的杀菌剂。公开了一种含有由式(I)表示的化合物的杀真菌组合物：其中R¹代表卤素原子，R²和R³各代表较低的烷基基团，R⁴代表或-CHF₂，或其酸盐加合物，并且至少含有一种具有麦角固醇生物合成抑制活性或细胞分裂抑制活性的杀菌剂。
• [EN] AMINOPYRIMIDINES AS SORBITOL DEHYDROGENASE INHIBITORS<br/>[FR] AMINOPYRIMIDINES COMME INHIBITEURS DE SORBITOL DESHYDROGENASE
  申请人：PFIZER PROD INC

  公开号：WO2000059510A1

  公开（公告）日：2000-10-12

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of formula (I), wherein R?1, R2 and R3¿ are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefor at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula (I) of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula (I) of this invention with an NHE-1 inhibitor and to methods of treating cardiomyopathy and other heart-related problems therewith. This invention is also directed to certain intermediates used in the synthesis of the compounds of formula (I) and to processes for preparing those intermediates.

  本发明涉及式（I）的山梨醇脱氢酶抑制剂，其中R1、R2和R3在说明书中定义。本发明还涉及含有这些化合物的药物组合物，以及通过将这些化合物用于患有糖尿病并因此有患上这些并发症风险的哺乳动物进行治疗或预防糖尿病并发症，特别是糖尿病神经病变、糖尿病肾病、糖尿病微血管病、糖尿病大血管病和糖尿病心肌病的方法。本发明还涉及一种包含本发明式（I）化合物和醛还原酶抑制剂的药物组合物以及用于治疗或预防糖尿病并发症的方法。本发明还涉及一种包含本发明式（I）化合物和NHE-1抑制剂的药物组合物以及用于治疗心肌病和其他心脏相关问题的方法。本发明还涉及用于合成式（I）化合物的某些中间体以及制备这些中间体的方法。
• Sorbitol dehydrogenase inhibitors
  申请人：——

  公开号：US20040077671A1

  公开（公告）日：2004-04-22

  This invention is directed to sorbitol dehydrogenase inhibitory compounds of the formula I, 1 wherein R 1 , R 2 and R 3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing those compounds and methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy and diabetic cardiomyopathy by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an aldose reductase inhibitor and to methods of treating or preventing diabetic complications therewith. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of this invention with an NHE-1 inhibitor and to methods of treating cardiomyopathy and other heart-related problems therewith. This invention is also directed to certain intermediates used in the synthesis of the compounds of formula I and to processes for preparing those intermediates.

  本发明涉及公式I的山梨醇脱氢酶抑制剂，其中R1、R2和R3如规范中所定义。本发明还涉及含有这些化合物的制药组合物以及通过向患有糖尿病且因此有发展这些并发症风险的哺乳动物投与这些化合物来治疗或预防糖尿病并发症，特别是糖尿病神经病、糖尿病肾病、糖尿病微血管病、糖尿病大血管病和糖尿病心肌病的方法。本发明还涉及一种公式I化合物与醛糖还原酶抑制剂的组合物制药组合物以及用于治疗或预防糖尿病并发症的方法。本发明还涉及一种公式I化合物与NHE-1抑制剂的组合物制药组合物以及用于治疗心肌病和其他心脏相关问题的方法。本发明还涉及用于合成公式I化合物的某些中间体以及制备这些中间体的方法。
• 3-Pyrrolidinylthio-1-azabicyclo(3,2,0) hept-2-ene-2-carboxylic acid compounds
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0343499A1

  公开（公告）日：1989-11-29

  A compound of the formula : in which R1 is carboxy or protected carboxy, R2 is hydroxy(lower)alkyl or protected hydroxy(lower)alkyl, R3 is hydrogen or lower alkyl, R4 is unsaturated heterocyclic group which may be substituted by suitable substituent(s), R5 is hydrogen, lower alkanimidoyl or imino-protective group, and A is lower alkylene, or pharmaceutically acceptable salts thereof, processes for their preparation and pharmaceutical compositions comprising them as an active ingredient in admixture with a pharmaceutically acceptable carrier or excipient.

  一种式......的化合物 其中 R1 是羧基或受保护的羧基 R2 是羟基（低级）烷基或受保护的羟基（低级）烷基 R3 是氢或低级烷基 R4 是不饱和杂环基，可被合适的取代基取代、 R5 是氢、低级烷酰基或亚氨基保护基团，以及 A 是低级亚烷基、 或它们的药学上可接受的盐、它们的制备工艺以及包含它们作为活性成分与药学上可接受的载体或赋形剂混合的药物组合物。