5-[2-(4-methoxyphenyl)ethyl]-1H-pyrazole-3-carboxylic acid | 681034-85-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[2-(4-methoxyphenyl)ethyl]-1H-pyrazole-3-carboxylic acid
• CAS: 681034-85-5
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: SZLCPGSMHAVXRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  75.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 5-[2-(4-methoxyphenyl)ethyl]-1H-pyrazole-3-carboxylate 在 甲醇 、 sodium hydroxide 、 水 、 盐酸 作用下， 以 水 为溶剂， 反应 0.5h， 生成 5-[2-(4-methoxyphenyl)ethyl]-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Pyrrole and pyrazole DAAO inhibitors

  摘要：

  增加D-丝氨酸浓度和减少D-丝氨酸氧化的有毒产物浓度的方法，用于增强学习、记忆和/或认知能力，或用于治疗精神分裂症、阿尔茨海默病、共济失调或神经病性疼痛，或预防神经元功能丧失，这涉及向需要治疗的受试者施用化合物I的治疗有效量，或其药学上可接受的盐或溶剂：其中R1和R2独立地选自氢、卤素、硝基、烷基、酰基、烷基芳基和XYR5；或R1和R2共同形成一个5、6、7或8-成员的取代或未取代的碳环或杂环基团；X和Y独立地选自O、S、NH和(CR6R7)n；R3为氢、烷基或M+；M为铝、钙、锂、镁、钾、钠、锌离子或其混合物；Z为N或CR4；R4选自氢、卤素、硝基、烷基、烷基芳基和XYR5；R5选自芳基、取代芳基、杂环芳基和取代杂环芳基；R6和R7独立地选自氢和烷基；n为1到6的整数；R1、R2和R4中至少有一个不是氢；X和Y中至少有一个是(CR6R7)n。 D-丝氨酸或环丝氨酸可以与化合物I的共同给药。

  公开号：

  US20050143443A1

文献信息

• [EN] 5-SUBSTITUTED 2H-PYRAZONE-3-CARBOXYLIC ACID DERIVATIVES AS ANTILIPOLYTIC AGENTS FOR THE TREATMENT OF METABOLIC-RELATED DISORDERS SUCH AS DYSLIPIDEMIA<br/>[FR] DERIVES D'ACIDE 2H-PYRAZOLE-3-CARBOXYLIQUE SUBSTITUE EN 5 UTILISES EN TANT QU'AGENTS ANTILIPOTYQUES POUR LE TRAITEMENT DE TROUBLES METABOLIQUES, TELS QUE LA DYSLIPIDEMIE
  申请人：ARENA PHARM INC

  公开号：WO2004032928A1

  公开（公告）日：2004-04-22

  The present invention relates to certain pyrazole carboxylic acid derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, as antilipolytic agents and against for the receptor RUP25, wherein: R2 is H, halogen, C1-12 alkyl or C1-12 haloalkyl; and R3 is C3-6 cycloalkyl, C1-12 alkyl, C1-12 haloalkyl, C3-6 cycloalkyl-C1-4-alkylene, aryl-C1-4-alkylene or heteroaryl-C1-4-alkylene, wherein said aryl-C1-4-alkylene and heteroaryl-C1-4-alkylene can be optionally substituted 1 to 5 substituents selected from the substituents listed in the claims. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for pharmaceutical compositions in combination with other active agents, for example, those agents belonging to the class of α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, thiazolidinedione and the like.

  本发明涉及具有化学式（Ia）的某些吡唑羧酸衍生物及其药学上可接受的盐，作为抗脂解作用剂和针对受体RUP25的药物，在该化合物中：R2为H、卤素、C1-12烷基或C1-12卤代烷基；R3为C3-6环烷基、C1-12烷基、C1-12卤代烷基、C3-6环烷基-C1-4-烷基、芳基-C1-4-烷基或杂环芳基-C1-4-烷基，其中所述的芳基-C1-4-烷基和杂环芳基-C1-4-烷基可以选择性地取代1至5个选自权利要求中所列取代基的取代基。本发明还提供了含有该化合物的药物组合物，以及在治疗代谢相关疾病，包括脂质代谢紊乱、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、综合征X等方面使用该化合物和组合物的方法。此外，本发明还提供了与其他活性剂结合的药物组合物，例如，属于α-葡萄糖苷酶抑制剂、醛糖还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烯合成抑制剂、贝特类药物、LDL降解增强剂、血管紧张素转化酶（ACE）抑制剂、胰岛素分泌增强剂、噻唑烷二酮类药物等类别的药物。
• 5-substituted 2h-pyrazone-3-carbixylic acid derivatives as antilipolytic agents for the treatment of metabolic-related disorders such as dyslipidemia
  申请人：Semple Graeme

  公开号：US20060167270A1

  公开（公告）日：2006-07-27

  The present invention relates to certain pyrazole carboxylic acid derivatives of Formula (Ia), and pharmaceutically acceptable salts thereof, as antilipolytic agents and against for the receptor RUP25, wherein: R 2 is H, halogen, C 1-12 alkyl or C 1-12 haloalkyl; and R 3 is C 3-6 cycloalkyl, C 1-12 alkyl, C 1-12 haloalkyl, C 3-6 cycloalkyl-C 1-4 -alkylene, aryl-C 1-4 -alkylene or heteroaryl-C 1-4 -alkylene, wherein said aryl-C 1-4 -alkylene and heteroaryl-C 1-4 -alkylene can be optionally substituted 1 to 5 substituents selected from the substituents listed in the claims. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, insulin resistance, type 2 diabetes, Syndrome-X and the like. In addition, the present invention also provides for pharmaceutical compositions in combination with other active agents, for example, those agents belonging to the class of α-glucosidase inhibitors, aldose reductase inhibitors, biguanides, HMG-CoA reductase inhibitors, squalene synthesis inhibitors, fibrates, LDL catabolism enhancers, angiotensin converting enzyme (ACE) inhibitors, insulin secretion enhancers, thiazolidinedione and the like.

  本发明涉及公式（Ia）的某些吡唑羧酸衍生物及其药学上可接受的盐，作为抗脂解作用剂和对RUP25受体的作用剂，其中：R2为H、卤素、C1-12烷基或C1-12卤代烷基；R3为C3-6环烷基、C1-12烷基、C1-12卤代烷基、C3-6环烷基-C1-4-烷基、芳基-C1-4-烷基或杂环芳基-C1-4-烷基，其中所述的芳基-C1-4-烷基和杂环芳基-C1-4-烷基可以选择性地被1至5个在权利要求书中列出的取代基所取代。本发明还提供了含有该化合物的药物组合物，并且提供了使用该化合物和该组合物治疗代谢相关疾病的方法，包括血脂异常、动脉粥样硬化、冠心病、胰岛素抵抗、2型糖尿病、X综合症等。此外，本发明还提供了与其他活性剂组合的药物组合物，例如属于α-葡萄糖苷酶抑制剂、醛还原酶抑制剂、双胍类、HMG-CoA还原酶抑制剂、角鲨烷合成抑制剂、纤维酸类、LDL降解增强剂、血管紧张素转换酶（ACE）抑制剂、胰岛素分泌增强剂、噻唑烷二酮等类别的活性剂。
• Pyrrole and Pyrazole DAAO Inhibitors
  申请人：Fang Q. Kevin

  公开号：US20100016397A1

  公开（公告）日：2010-01-21

  Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R 1 and R 2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR 5 ; or R 1 and R 2 , taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR 6 R 7 ) n ; R 3 is hydrogen, alkyl or M + ; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR 4 ; R 4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR 5 ; R 5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R 6 and R 7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R 1 , R 2 and R 4 is other than hydrogen; and at least one of X and Y is (CR 6 R 7 ) n . D-serine or cycloserine may be coadministered along with the compound of formula I.

  增加D-丝氨酸浓度并减少D-丝氨酸氧化产物浓度的方法，以增强学习、记忆和/或认知能力，或治疗精神分裂症、阿尔茨海默病、共济失调或神经病理性疼痛，或预防神经退行性疾病特征性神经元功能损失，包括向需要治疗的受试者施用公式I的化合物或其药学上可接受的盐或溶剂的治疗有效量：其中，R1和R2分别选自氢、卤素、硝基、烷基、酰基、烷基芳基和XYR5；或R1和R2共同形成5、6、7或8成员取代或未取代的碳环或杂环基；X和Y分别选自O、S、NH和（CR6R7）n；R3为氢、烷基或M+；M为铝离子、钙离子、锂离子、镁离子、钾离子、钠离子、锌离子或其混合物；Z为N或CR4；R4选自氢、卤素、硝基、烷基、烷基芳基和XYR5；R5选自芳基、取代芳基、杂芳基和取代杂芳基；R6和R7分别选自氢和烷基；n为1到6的整数；R1、R2和R4中至少有一个不是氢；X和Y中至少有一个是（CR6R7）n。D-丝氨酸或环丝氨酸可以与公式I的化合物一起共同施用。
• PYRROLE AND PYRAZOLE DAAO INHIBITORS
  申请人：FANG Q. Kevin

  公开号：US20110092559A1

  公开（公告）日：2011-04-21

  Methods for increasing D-Serine concentration and reducing concentration of the toxic products of D-Serine oxidation, for enhancing learning, memory and/or cognition, or for treating schizophrenia, Alzheimer's disease, ataxia or neuropathic pain, or preventing loss in neuronal function characteristic of neurodegenerative diseases involve administering to a subject in need of treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof: wherein R 1 and R 2 are independently selected from hydrogen, halo, nitro, alkyl, acyl, alkylaryl, and XYR 5 ; or R 1 and R 2 , taken together, form a 5, 6, 7 or 8-membered substituted or unsubstituted carbocyclic or heterocyclic group; X and Y are independently selected from O, S, NH, and (CR 6 R 7 ) n ; R 3 is hydrogen, alkyl or M + ; M is aluminum, calcium, lithium, magnesium, potassium, sodium, zinc ion or a mixture thereof; Z is N or CR 4 ; R 4 is from selected from hydrogen, halo, nitro, alkyl, alkylaryl, and XYR 5 ; R 5 is selected from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R 6 and R 7 are independently selected from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R 1 , R 2 and R 4 is other than hydrogen; and at least one of X and Y is (CR 6 R 7 ) n . D-serine or cycloserine may be coadministered along with the compound of formula I.

  增加D-丝氨酸浓度和减少D-丝氨酸氧化的有毒产物浓度的方法，以增强学习、记忆和/或认知能力，或用于治疗精神分裂症、阿尔茨海默病、共济失调或神经病理性疼痛，或预防神经退行性疾病特征性神经元功能丧失，包括向需要治疗的受试者施用公式I的化合物的治疗有效量，或其药学上可接受的盐或溶剂：其中，R1和R2分别选自氢、卤、硝基、烷基、酰基、烷基芳基和XYR5；或R1和R2一起形成一个5、6、7或8成员的取代或未取代的碳环或杂环基；X和Y分别选自O、S、NH和（CR6R7）n；R3是氢、烷基或M+；M是铝、钙、锂、镁、钾、钠、锌离子或其混合物；Z是N或CR4；R4选自氢、卤、硝基、烷基、烷基芳基和XYR5；R5选自芳基、取代芳基、杂芳基和取代杂芳基；R6和R7分别选自氢和烷基；n是1到6的整数；R1、R2和R4中至少有一个不是氢；X和Y中至少有一个是（CR6R7）n。D-丝氨酸或环丝氨酸可以与公式I的化合物一起共同施用。
• 5-SUBSTITUTED 2H-PYRAZONE-3-CARBOXYLIC ACID DERIVATIVES AS ANTILIPOLYTIC AGENTS FOR THE TREATMENT OF METABOLIC-RELATED DISORDERS SUCH AS DYSLIPIDEMIA
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP1551403A1

  公开（公告）日：2005-07-13