1-benzyl-3-hydroxy-5-methoxycarbonyl-1H-pyrazole | 52867-49-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-benzyl-3-hydroxy-5-methoxycarbonyl-1H-pyrazole
• 英文别名: 2-benzyl-5-oxo-2,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester；methyl 2-benzyl-5-hydroxy-2H-pyrazole-3-carboxylate；methyl 1-benzyl-3-hydroxy-1H-pyrazole-5-carboxylate；1-benzyl-3-hydroxy-1H-pyrazole-5-carboxylic acid methyl ester；methyl 2-benzyl-5-oxo-1H-pyrazole-3-carboxylate
• CAS: 52867-49-9
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: UFYYVUADSYAISN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyl-3-hydroxy-5-methoxycarbonyl-1H-pyrazole 在 sodium hydroxide 、 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 1-benzyl-3-(3-di-methylaminopropyloxy)-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Pyrazoles and Indazoles as Activators of the Nitric Oxide Receptor, Soluble Guanylate Cyclase

  摘要：

  Database searching and compound screening identified 1-benzyl-3-(3-dimethylaminopropyloxy)-indazole (benzydamine, 3) as a potent activator of the nitric oxide receptor, soluble guanylate cyclase. A comprehensive structure-activity relationship study surrounding 3 clearly showed that the indazole C-3 dimethylaminopropyloxy substituent was critical for enzyme activity. However replacement of the indazole ring of 3 by appropriately substituted pyrazoles maintained enzyme activity. Compounds were evaluated for inhibition of platelet aggregation and showed a general lipophilicity requirement. Aryl-substituted pyrazoles 32, 34, and 43 demonstrated potent activation of soluble guanylate cyclase and potent inhibition of platelet aggregation. Pharmacokinetic studies in rats showed that compound 32 exhibits modest oral bioavailability (12%). Furthermore 32 has an excellent selectivity profile notably showing no significant inhibition of phosphodiesterases or nitric oxide synthases.

  DOI：

  10.1021/jm001034k
• 作为产物：
  描述：

  5-羟基-吡唑-3-羧酸甲酯 、 溴甲苯 在 potassium carbonate 作用下， 以 异丙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 以22%的产率得到1-benzyl-3-hydroxy-5-methoxycarbonyl-1H-pyrazole
  参考文献：
  名称：

  EP1829863

  摘要：

  公开号：

文献信息

• Benzimidazole derivatives and their use as KDR kinase protein inhibitors
  申请人：Babin Didier

  公开号：US20050009894A1

  公开（公告）日：2005-01-13

  The invention discloses and claims benzimidazole compounds of formula (I): wherein X is C—R2; Y is C—R2 or C—R3; W and Z are each C—R3; R1 is an optionally substituted aryl, heteroaryl or a saturated 5- or 6-membered monocyclic heterocyclic radical or a bicyclic heterocyclic radical; and A5 is H or alkyl; or a stereoisomer, a racemate, an enantiomer or a diastereoisomer of said compound of formula (I) or a pharmaceutically acceptable salt thereof; the use of compounds of formula (I) for the treatment of a disorder of proliferation of blood vessels, uncontrolled angiogenesis, a fibrotic disorder, a disorder of proliferation of mesangial cells, a metabolic disorder, allergy, asthma, thrombosis, a disease of the nervous system, retinopathy, psoriasis, rheumatoid arthritis, diabetes, muscle degeneration, solid tumors and cancers, pharmaceutical compositions comprising a compound of formula (I) and one or more pharmaceutically acceptable adjuvants or diluents and pharmaceutical compositions comprising a compound of formula (I) and one or more. antimitiotic agents.

  该发明公开和要求具有以下结构的苯并咪唑化合物（I）：其中X为C—R2；Y为C—R2或C—R3；W和Z均为C—R3；R1为选择性取代的芳基、杂环芳基或饱和的5-或6-成员单环杂环基或双环杂环基；A5为H或烷基；或者为该化合物的立体异构体、拉克酸盐、对映异构体或二对映异构体；该化合物的用途为治疗血管增殖障碍、不受控制的血管生成、纤维化障碍、系膜细胞增殖障碍、代谢障碍、过敏、哮喘、血栓形成、神经系统疾病、视网膜病变、银屑病、类风湿性关节炎、糖尿病、肌肉退化、实体肿瘤和癌症的药物组合物包括化合物（I）和一个或多个药用辅料或稀释剂，以及包括化合物（I）和一个或多个抗有丝分裂剂的药物组合物。
• [EN] ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE<br/>[FR] ACTIVATEURS DE GUANYLATE CYCLASE SOLUBLE
  申请人：UNIV LONDON

  公开号：WO2000027394A1

  公开（公告）日：2000-05-18

  The present invention describes the use of pyrazole or indazole derivates as activators of soluble guanylate cyclase. Some compounds disclosed are novel. All activators are vasodilators and/or inhibit platelet aggregation and are therefore useful in the treatment of peripheral vascular diseases such as hypertension, angina pectoris or atherosclerosis, or in the treatment of prevention of glaucoma, preeclampsia, Raynaud's syndrome, stroke or erectile disfunctions.

  本发明描述了将吡唑或吲唑衍生物用作可溶性鸟苷酸环化酶的激活剂。其中一些化合物是新颖的。所有激活剂均为血管扩张剂和/或抑制血小板聚集剂，因此可用于治疗外周血管疾病，如高血压、心绞痛或动脉粥样硬化，或用于预防青光眼、先兆子痫、雷诺综合征、中风或勃起功能障碍。
• Benzimidazoles
  申请人：Edwards L. Michael

  公开号：US20060014756A1

  公开（公告）日：2006-01-19

  The invention is directed to physiologically active compounds of the general formula (Ix) and compositions containing such compounds, and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (Ix), and to processes for their preparation. Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit kinases.

  本发明涉及一般式（Ix）的生理活性化合物及含有这种化合物的组合物，以及它们的前药、药学上可接受的盐和溶剂化物，还涉及在式（Ix）范围内的新化合物和它们的制备方法。这种化合物和组合物具有有价值的药物性质，特别是抑制激酶的能力。
• Arylalkanoic Acid Derivative
  申请人：Maekawa Tsuyoshi

  公开号：US20080051418A1

  公开（公告）日：2008-02-28

  A compound represented by the formula (I): wherein Ar is an optionally substituted aromatic ring; Xa, Xc, Ya, Yc, Z 1 and Z 2 are each a bond, O, S, —CO—, —CS—, —CR 3 (OR 4 )—, —NR 5 —, —SO—, —SO 2 —, —CONR 6 — or —NR 6 CO— (wherein R 3 , R 4 , R 5 and R 6 are as defined in the specification); Xb and Yb are each a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R 1 is an optionally substituted hydrocarbon group; ring A is an optionally further substituted aromatic ring, provided that the ring should not be benzimidazole; n is an integer of 1 to 8; ring B is an optionally further substituted aromatic ring, provided that the ring should not be oxazole; W is a divalent saturated hydrocarbon group having 1 to 20 carbon atoms; and R 2 is —OR 8 or —NR 9 R 10 (wherein R 8 , R 9 and R 10 are as defined in the specification) or a salt thereof, is useful as an agent for the prophylaxis or treatment of diabetes and the like.

  化合物式(I)所代表的复合物，其中Ar是一个可选择性取代的芳香环；Xa、Xc、Ya、Yc、Z1和Z2分别是键合、O、S、—CO—、—CS—、—CR3(OR4)—、—NR5—、—SO—、—SO2—、—CONR6—或—NR6CO—（其中R3、R4、R5和R6如规范中所定义）；Xb和Yb分别是一个键合或具有1到20个碳原子的二价碳氢基团；R1是一个可选择性取代的碳氢基团；环A是一个可选择性进一步取代的芳香环，但不应为苯并咪唑；n是1到8的整数；环B是一个可选择性进一步取代的芳香环，但不应为噁唑；W是一个具有1到20个碳原子的二价饱和碳氢基团；和R2是—OR8或—NR9R10（其中R8、R9和R10如规范中所定义）或其盐，用作预防或治疗糖尿病等疾病的药剂。
• Benzimidazole derivatives and their use as kdr kinase protein inhibitors
  申请人：Babin Didier

  公开号：US20080125418A1

  公开（公告）日：2008-05-29

  The invention discloses and claims benzimidazole compounds of formula (I): wherein X is C—R2; Y is C—R2 or C—R3; W and Z are each C—R3; R1 is an optionally substituted aryl, heteroaryl or a saturated 5- or 6-membered monocyclic heterocyclic radical or a bicyclic heterocyclic radical; and A5 is H or alkyl; or a stereoisomer, a racemate, an enantiomer or a diastereoisomer of said compound of formula (I) or a pharmaceutically acceptable salt thereof; the use of compounds of formula (I) for the treatment of a disorder of proliferation of blood vessels, uncontrolled angiogenesis, a fibrotic disorder, a disorder of proliferation of mesangial cells, a metabolic disorder, allergy, asthma, thrombosis, a disease of the nervous system, retinopathy, psoriasis, rheumatoid arthritis, diabetes, muscle degeneration, solid tumors and cancers, pharmaceutical compositions comprising a compound of formula (I) and one or more pharmaceutically acceptable adjuvants or diluents and pharmaceutical compositions comprising a compound of formula (I) and one or more. antimitotic agents.

  本发明揭示和声明了式（I）的苯并咪唑化合物：其中X是C-R2; Y是C-R2或C-R3; W和Z均为C-R3; R1是可选择取代的芳基，杂芳基或饱和的5-或6-成员单环杂环基或双环杂环基; A5是H或烷基; 或者是式（I）的立体异构体，外消旋体，对映异构体或二对映异构体或其药学上可接受的盐; 本发明还涉及使用式（I）的化合物治疗血管增殖障碍，无控制的血管生成，纤维化障碍，系膜细胞增殖障碍，代谢障碍，过敏，哮喘，血栓形成，神经系统疾病，视网膜病变，牛皮癣，类风湿性关节炎，糖尿病，肌肉退化，实体瘤和癌症的药物组合物，包括式（I）的化合物和一个或多个药学上可接受的辅料或稀释剂以及包括式（I）的化合物和一个或多个抗有丝分裂剂的药物组合物。