methyl 4-(2-fluorobenzoyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate | 111596-00-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-(2-fluorobenzoyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate
• CAS: 111596-00-0
• 化学式: C₁₅H₁₄FNO₃
• 分子量: 275.279
• InChiKey: BLKHMBZKILQEJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,5-二氯吡咯-3-羧酸甲酯 、 邻氟苯甲酰氯 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 以77%的产率得到methyl 4-(2-fluorobenzoyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  苯甲酰基吡咯型钙通道活化剂的极短合成

  摘要：

  2,5-二甲基吡咯-3-羧酸甲酯与2-氯甲基苯甲酰氯的Friedel-Crafts酰化反应生成相应的4-（2-氯甲基苯甲酰基）吡咯，其与苯和氯化铝原位反应，生成新型钙通道活化剂FPL 64176 。

  DOI：

  10.1016/0040-4039(92)89013-3

文献信息

• An extremely short synthesis of benzoylpyrrole-type calcium channel activators
  作者：Christopher R. Dalton、John M. Kane、David Rampe

  DOI：10.1016/0040-4039(92)89013-3

  日期：1992.9

  Friedel-Crafts acylation of methyl 2,5-dimethylpyrrole-3-carboxylate with 2-chloromethylbenzoyl chloride generated the corresponding 4-(2-chloromethylbenzoyl)pyrrole which was reacted in situ with benzene and aluminum chloride to yield the novel calcium channel activator FPL 64176.

  2,5-二甲基吡咯-3-羧酸甲酯与2-氯甲基苯甲酰氯的Friedel-Crafts酰化反应生成相应的4-（2-氯甲基苯甲酰基）吡咯，其与苯和氯化铝原位反应，生成新型钙通道活化剂FPL 64176 。
• Pharmacologically active pyrrole and pyrazole derivatives
  申请人：FISONS plc

  公开号：EP0230110A1

  公开（公告）日：1987-07-29

  There are described compounds of formula I, wherein either one of Y and Z (which may be the same or different) represents CH, CR2 or C-COOR21, in which R2 represents alkyl C 1 to C6 optionally substituted by halogen, hydroxy, amino, isothioureido or a group R5COO- in which R5 represents alkyl C 1 to C6, R2 being optionally interrupted by O or S, and R21 represents alkyl C 1 to C6, and the other one of Y and Z represents CR2 or C-COOR21, or one of Y and Z represents N and the other CH, CR2 or C-COOR21, R4 represents Ar1-B-(W)x, in which W represents C=O, S, SO, SO2 or C=N-OH, x represents 0 or 1, B represents a single bond or (CH2)p in which p represents 1 or 2, the group (CH2)p being optionally substituted by alkyl C1 to Ar1 represents phenyl, naphthyl or benzofurazanyl, Ar1 being optionally substituted by one or more of X, CX3, OCHnX3-n, hydroxy, alkyl C 1 to C6, Oalkyl C 1 to C6, nitro, amino, carboxy, -SCH2Ar2, -OCH2Ar2 or -OCOAr2 in which X represents halogen, n represents 0,1, 2 or 3, and Ar2 represents phenyl or phenyl substituted by hydroxy, halogen, alkyl C 1 to C6 or Oalkyl C 1 to C6, and R3 and R1 are as defined in the specification. There are also described processes for the preparation of compounds of formula I and pharmaceutical, eg cardiovascular, compositions containing them.

  所述化合物为式 I、 式中 Y和Z（可以相同或不同）中的一个代表CH、CR2或C-COOR21，其中R2代表任选被卤素、羟基、氨基、异硫脲基或基团R5COO-取代的C 1至C6烷基，其中R5代表C 1至C6烷基，R2任选被O或S打断，R21代表C 1至C6烷基，Y和Z中的另一个代表CR2或C-COOR21、 或 Y 和 Z 中的一个代表 N，另一个代表 CH、CR2 或 C-COOR21、 R4 代表 Ar1-B-(W)x，其中 W 代表 C=O、S、SO、SO2 或 C=N-OH、 x 代表 0 或 1、 B 代表单键或 (CH2)p，其中 p 代表 1 或 2，(CH2)p 组可选择被烷基 C1 至 C2 取代。 Ar1 代表苯基、萘基或苯并呋喃基，Ar1 可任选被一个或多个 X、CX3、OCHnX3-n、羟基、C 1 至 C6 烷基、C 1 至 C6 氧代烷基、硝基、氨基、羧基、-SCH2Ar2、-OCH2Ar2 或 -OCOAr2 取代，其中 X 代表卤素 n 代表 0、1、2 或 3，以及 Ar2 代表苯基或被羟基、卤素、C 1 至 C6 烷基或 C 1 至 C6 O 烷基取代的苯基，以及 R3 和 R1 如说明书中所定义。 还描述了制备式 I 化合物和含有它们的药物（如心血管）组合物的工艺。
• Discovery and synthesis of methyl 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate (FPL 64176) and analogs: the first examples of a new class of calcium channel activator
  作者：Andrew J. G. Baxter、John Dixon、Francis Ince、Carol N. Manners、Simon J. Teague

  DOI：10.1021/jm00071a004

  日期：1993.9

  Methyl 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylate, FPL 64176 (1), is the first example of a new class of calcium channel activator (CCA) that does not act on any of the well-defined calcium channel modulator receptor sites, as typified by verapamil, diltiazem, and the dihydropyridines. The potent activity of 1, having the 2-(phenylmethyl)benzoyl substituent, was predicted using QSAR on an initial set of less potent benzoylpyrroles. When compared to the CCA Bay K 8644, 1 has simialr potency on calcium uptake into GH3 cells (both have EC50 approximately 0.015 muM) but is appreciably more potent functionally at increasing contractility in a guinea pig atria preparation (1 has EC50 = 0.049 muM vs Bay K 8644 EC50 = 1.95 muM). 1 is an achiral, pharmacologically clean agonist with no demonstrable partial agonist properties and possesses appreciably higher efficacy than Bay K 8644. It should therefore become a useful biochemical and pharmacological tool for the study of calcium channels in many cell types.