1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester | 887703-74-4

• 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-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester
• 英文别名: 1-(4-fluoro-phenyl)-4-isopropyl-1 H-pyrazole-3,5-dicarboxylic acid 3-methyl ester；2-(4-fluorophenyl)-5-methoxycarbonyl-4-propan-2-ylpyrazole-3-carboxylic acid
• CAS: 887703-74-4
• 化学式: C₁₅H₁₅FN₂O₄
• 分子量: 306.294
• InChiKey: ASTVVQBHDKWAPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.83h， 以90%的产率得到1-(4-fluorophenyl)-5-hydroxymethyl-4-isopropyl-1H-pyrazole-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Novel pyrazole-based HMG CoA reductase inhibitors

  摘要：

  描述了作为降胆固醇和降脂血症药物的新化合物和制剂。更具体地，描述了对酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的强效抑制剂。还描述了使用这些化合物和制剂来治疗患有高脂血症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、阿尔茨海默病、良性前列腺肥大（BPH）、糖尿病和骨质疏松症等疾病的受试者，包括人类的方法。

  公开号：

  US20060111422A1
• 作为产物：
  描述：

  3-甲基-1-(p-氟苯基)-4-异丙基-1H-吡唑-3,5-二羧酸-5-苄酯 在 钯 氮 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以to afford 1-(4-fluoro-phenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester (14.6g, 99%) in sufficient purity for use in the next step的产率得到1-(4-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 3-methyl ester
  参考文献：
  名称：

  NOVEL PYRAZOLE-BASED HMG CoA REDUCTASE INHIBITORS

  摘要：

  本文描述了一种新型化合物和制药组合物，可用作降低胆固醇和脂质的药物。更具体地说，本文描述了一种酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的有效抑制剂。本文还描述了使用这些化合物和组合物治疗患有高脂血症、高胆固醇血症、高三酰甘油血症、动脉粥样硬化、阿尔茨海默病、良性前列腺增生症（BPH）、糖尿病和骨质疏松症等疾病的受试者，包括人类的方法。

  公开号：

  US20090170852A1

文献信息

• Pyrazole-based HMG CoA reductase inhibitors
  申请人：Pfizer Inc.

  公开号：US07446121B2

  公开（公告）日：2008-11-04

  Novel compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents are described. More specifically, potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (“HMG CoA reductase”) are described. Methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis are also described.

  本文描述了作为降低胆固醇和脂质的药物的新化合物和制药组合物。更具体地，描述了强效的酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的抑制剂。还描述了使用这些化合物和组合物治疗患有高脂血症、高胆固醇血症、高三酰甘油血症、动脉硬化、阿尔茨海默病、良性前列腺肥大、糖尿病和骨质疏松症等病症的受试者，包括人类的方法。
• Substituted Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery of (3<i>R</i>,5<i>R</i>)-7-[2-(4-Fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2<i>H</i>-pyrazol-3-yl]-3,5-dihydroxyheptanoic Acid (PF-3052334) as a Candidate for the Treatment of Hypercholesterolemia
  作者：Jeffrey A. Pfefferkorn、Chulho Choi、Scott D. Larsen、Bruce Auerbach、Richard Hutchings、William Park、Valerie Askew、Lisa Dillon、Jeffrey C. Hanselman、Zhiwu Lin、Gina H. Lu、Andrew Robertson、Catherine Sekerke、Melissa S. Harris、Alexander Pavlovsky、Graeme Bainbridge、Nicole Caspers、Mark Kowala、Bradley D. Tait

  DOI：10.1021/jm070849r

  日期：2008.1.1

  In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.
• 7-(2H-PYRAZOL-3-YL)-3,5-DIHYDROXY-HEPTANOIC ACID DERIVATIVES AS HMG CO-A REDUCTASE INHIBITORS FOR THE TREATMENT OF LIPIDEMIA
  申请人：Warner-Lambert Company LLC

  公开号：EP1819681B1

  公开（公告）日：2009-08-12
• US7446121B2
  申请人：——

  公开号：US7446121B2

  公开（公告）日：2008-11-04
• [EN] 7-(2H-PYRAZOL-3-YL)-3, 5-DIHYROXY-HEPTANOIC ACID DERIVATIVES AS HMG CO-A REDUCTASE INHIBITORS FOR THE TREATMENT OF LIPIDEMIA<br/>[FR] DERIVES D'ACIDE 7-(2H-PYRAZOL-3-YL)-3, 5-DIHYROXY-HEPTANOIQUE COMME INHIBITEURS DE HMG CO-A REDUCTASE POUR LE TRAITEMENT DE L'HYPERLIPIDEMIE
  申请人：WARNER LAMBERT CO

  公开号：WO2006056845A1

  公开（公告）日：2006-06-01

  [EN] The present invention provides compounds of the formula (I), (IV) and (V) and intermediates of the formuale (VI) and (VII): (I), (IV), (V), (VI), (VII). wherein: R₁ is hydrogen, halogen, C₁-C₇ alkyl, C₃-C₈ cycloalkyl, aryl, aralkyl, heteroaryt, or heteroaralkyl; more specifically, R₁ is C₁-C₇ alkyl or C₃-C₈ cycloalkyl; even more specifically, R₁ is isopropyl; where alkyl, cycloalkyt, aryl, aralkyt, heteroaryl, or heteroaralkyl of R₁ is optionally substituted, R₂ is hydrogen, halogen, C₁-C₇ alkyl, C₃-C₈ cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, NC-, R_2bR_2aNCO(CH₂)_n -, R_2bR_2a NS(O)_n-, R_2cS(O)_n-, R_2bR_2a N(CH₂)_n-, R_2b-J-C(O)NR_2a(CH2)_n-, R_2b-J-­SO₂NR_2a(CH₂)_n-, R_2b-J-SONR_2a(CH₂)_n, R⁷OOC(CH₂)_n-, or R⁷CO(CH₂)_n-; more specifically, R₂ is R_2bR_2aNCO(CH₂)_n-; even more specifically, R₂ is R_2bR_2a NCO-; where alkyl, cycloalkyl, aryl , aralkyl, heteroaryl, or heteroaralkyl of R₂ is optionally substituted, R₃ is hydrogen, C_1-6 aikyl, C_3-6necycloafkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; more specifically, R₃ is aryl; even more specifically, R₃ is phenyl or p-fluorophenyl; where alkyl, cycloalkyl, aryl, aralkyl, heteroaryt, or beteroaralkyd of A₃ is opltianally substituted and is a bond or is absent. The other substituents are defined in the claims. The present invention relates to compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents. Moree specifically, the present invention concerns certain potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase ("HMG CoA reciuctase"). The compounds are useful for the treatement of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis.
  [FR] L'invention concerne des composés de formule (I), (IV) et (V) et des intermédiaires de formule (VI) et (VII): (I), (IV), (V), (VI), (VII): R₁ est hydrogène, halogène, C₁-C₇ alkyle, C₃-C₈ cycloalkyle, aryle, aralkyle, hétéroaryle, ou hétéroaralkyle; plus précisément, R₁ est C₁-C₇ alkyle ou C₃-C₈ cycloalkyle; plus précisément encore, R₁ est isopropyle; sachant que alkyle, cycloalkyle, aryle, aralkyle, hétéroaryle, ou hétéroaralkyle de R₁ est éventuellement substitué, R₂ est hydrogène, halogène, C₁-C₇ alkyle, C₃-C₈ cycloalkyle, aryle, aralkyle, hétéroaryle, hétéroaralkyle, NC-, R_2bR_2aNCO(CH₂)_n -, R_2bR_2a NS(O)_n-, R_2cS(O)_n-, R_2bR_2a N(CH₂)_n-, R_2b-J-C(O)NR_2a(CH2)_n-, R_2b-J--SO₂NR_2a(CH₂)_n-, R_2b-J-SONR_2a(CH₂)_n, R⁷OOC(CH₂)_n-, ou R⁷CO(CH₂)_n-; plus précisément, R₂ est R_2bR_2a NCO(CH₂)_n-; plus précisément encore, R₂ est R_2bR_2a NCO-; sachant que alkyle, cycloalkyle, aryle, aralkyle, hétéroaryle, ou hétéroaralkyle de R₂ est éventuellement substitué, R₃ est hydrogène, C_1-6 alkyle, C_3-8 cycloalkyle, aryle, aralkyle, hétéroaryle, ou hétéroaralkyle; plus précisément, R₃ est aryle; plus précisément encore, R₃ est phényle ou p-fluorophényle; sachant que alkyle, cycloalkyle, aryle, aralkyle, hétéroaryle, ou hétéroaralkyle de R₃ est éventuellement substitué et que - - - est une liaison ou n'est pas présent. On décrit des composés et des compositions pharmaceutiques utiles comme agents hypocholestérolémiques et hypolipidémiques. Plus précisément, on décrit certains inhibiteurs puissants de l'enzyme 3-hydroxy-3-méthylglutaryl-coenzyme A réductase ("HMG CoA réductase"). Les composés considérés sont utiles pour le traitement de l'hyperlipidémie, de l'hypercholestérolémie, de l'hypertriglycéridémie, de l'athérosclérose, de la maladie d'Alzheimer's, de l'hypertrophie prostatique bénigne, du diabète et de l'ostéoporose.