5-ethyl-4-fluoro-1H-pyrazole-3-carboxylic acid | 681034-63-9

• 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-ethyl-4-fluoro-1H-pyrazole-3-carboxylic acid
• CAS: 681034-63-9
• 化学式: C₆H₇FN₂O₂
• 分子量: 158.132
• InChiKey: YHRGYNURXYGNCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-ethyl-4-fluoro-1H-pyrazole-3-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以88%的产率得到5-ethyl-4-fluoro-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a

  摘要：

  A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.101

文献信息

• [EN] MORPHOLIN-PYRIDINE DERIVATIVES<br/>[FR] DÉRIVÉS MORPHOLINE-PYRIDINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015165835A1

  公开（公告）日：2015-11-05

  The present invention relates to compounds of formula (I) wherein X is CR or N; R is hydrogen, halogen or lower alkyl; L is a bond, -C(O)- or -C(O)NH-; Ar is phenyl or a five or six membered heteroaryl group, containing one or two N atoms; R1 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen or cycloalkyl; n is 0, 1, 2 or 3; or to a pharmaceutically suitable acid addition salt thereof, to all racemic mixtures, all their corresponding enantiomers and/or optical isomers, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

  本发明涉及以下式（I）的化合物，其中X为CR或N；R为氢、卤素或较低的烷基；L为键，-C（O）-或-C（O）NH-；Ar为苯基或含有一个或两个N原子的五元或六元杂环芳基；R1为卤素、较低的烷基、被卤素取代的较低烷基、较低的烷氧基、被卤素取代的较低烷氧基或环烷基；n为0、1、2或3；或其药学适宜的酸加合物，所有外消旋混合物，所有对应的对映体和/或光学异构体，可用于治疗抑郁症、焦虑症、双相情感障碍、注意缺陷多动障碍（ADHD）、与压力有关的障碍、精神障碍、精神分裂症、神经疾病、帕金森病、神经退行性疾病、阿尔茨海默病、癫痫、偏头痛、高血压、物质滥用、代谢障碍、进食障碍、糖尿病、糖尿病并发症、肥胖症、血脂异常、能量消耗和吸收障碍、体温稳态障碍和功能障碍、睡眠和昼夜节律障碍，以及心血管疾病。
• [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。
• PYRAZOLE DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Xiong Yifeng

  公开号：US20100004264A1

  公开（公告）日：2010-01-07

  Pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the serotonin 5HT 2A receptor. Formula (Ia). Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de Ia Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

  化合物公式（Ia）的吡唑衍生物及其药物组成物可调节5HT2A血清素受体的活性。化合物公式（Ia）及其药物组成物用于治疗失眠和相关睡眠障碍、血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、心房颤动、降低血栓形成的风险、哮喘或其症状、激动或其症状、行为障碍、药物引起的精神病、兴奋性精神病、Gilles de Ia Tourette综合征、躁狂障碍、有机或NOS精神病、精神病性障碍、急性精神分裂症、慢性精神分裂症、NOS精神分裂症及相关障碍、糖尿病相关障碍、进行性多灶性白质脑病等。本发明还涉及联合单独或同时给予其他药物制剂的方法，用于治疗5-HT2A血清素受体介导的疾病。
• Primary Amines And Derivatives Thereof As Modulators Of The 5-HT2A Serotonin Receptor Useful For The Treatment Of Disorders Related Thereto
  申请人：TEEGARDEN BRADLEY

  公开号：US20120270861A1

  公开（公告）日：2012-10-25

  The present invention pertains to certain compounds of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, asthma or symptoms thereof, agitation or a symptom thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor associated disorders in combination with other pharmaceutical agents administered separately or together.

  本发明涉及式(Ia)的某些化合物及其制药组合物，这些化合物调节5-HT2A 5-羟色胺受体的活性。这些化合物及其制药组合物用于治疗血小板聚集、冠状动脉疾病、心肌梗死、短暂性脑缺血发作、心绞痛、中风、心房颤动、血栓形成、哮喘或其症状、激动或其症状、行为障碍、药物诱导的精神病、兴奋性精神病、Gilles de la Tourette综合征、躁狂障碍、器质性或非器质性精神病、精神病、急性精神分裂症、慢性精神分裂症、非特异性精神分裂症及相关疾病以及睡眠障碍、糖尿病相关疾病、进行性多灶性白质脑病等方面的治疗方法。本发明还涉及与其他药物分别或同时给予的联合治疗5-HT2A 5-羟色胺受体相关疾病的方法。