CR2361 | 137795-86-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: CR2361
• 英文别名: (4R)-4-azaniumyl-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoate
• CAS: 137795-86-9
• 化学式: C₁₃H₂₄N₂O₃
• 分子量: 256.345
• InChiKey: VCRGLZYPNNAVRP-SNVBAGLBSA-N

物化性质

• 沸点：
  477.1±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  CR2361 、 螺谷胺 在 氯甲酸乙酯 、 三乙胺 作用下， 生成 (4R)-4-[[(4R)-5-(8-azaspiro[4.5]decan-8-yl)-4-[(3,5-dichlorobenzoyl)amino]-5-oxopentanoyl]amino]-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Structure−Antigastrin Activity Relationships of New Spiroglumide Amido Acid Derivatives

  摘要：

  A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbit gastric parietal cells. Appropriate chemical manipulations of the structure of spiroglumide (CR 2194), i.e., (R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro[4,5]decan-8-yl)-5-oxopentanoic acid, led to potent and selective antagonists of CCKB/gastrin receptors. Structure-activity relationships are discussed. Some of these new derivatives, as, for example, compound 54 (CR 2622), i.e., (S)-4-[[(R)-4'-[(3,5-dichlorobenzoyl)amino]-5'-(8-azaspiro[4.5] decan-8-yl)-5'-oxo-pentanonyl]amino]-5-(1-naphthylamino)-5- oxopentanoic acid, exhibit activity 70-170 times greater than that of spiroglumide, depending upon the model used (IC50 = 2 x 10(-8) vs 140 x 10(-8) mol in binding inhibition of [H-3]-N-Me-N-Leu-CCK-8 in guinea pig brain cortex and IC50 = 0.7 x 10(-8) vs 122.3 x 10(-8) mol in inhibition of gastrin-induced Ca2+ mobilization in parietal cells of rabbit, respectively). Computer-assisted conformational analysis studies were carried out in order to compare the chemical structure of both the agonist (pentagastrin) and the antagonist (54).

  DOI：

  10.1021/jm950372w
• 作为产物：
  描述：

  (R)-4-Benzyloxycarbonylamino-4-(4,4-dimethyl-cyclohexylcarbamoyl)-butyric acid benzyl ester 在 palladium on activated charcoal 水 、 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 CR2361
  参考文献：
  名称：

  新的（R）-4-苯甲酰胺基-5-氧戊酸衍生物的结构-抗胃泌素活性关系。

  摘要：

  通过立体保守方法合成了新的（R）-4-benzamido-5-oxopentanoic酸衍生物，并在体外评估了其抑制[125I]（BH）-CCK-8与任一大鼠外周血（CCK-A）结合的能力）或中枢（CCK-B）CCK受体，或[3H] pentagastrin与兔胃腺的结合，以及在体内抑制五肽胃泌素在灌注的大鼠胃中输注所诱导的酸分泌。该系列的母体化合物（洛格米特）是CCK-A受体的第一种非肽类，有效和选择性拮抗剂。化学处理洛格鲁胺的结构导致发现CCK-B /胃泌素受体的选择性拮抗剂。讨论了构效关系。其中一些新衍生物与兔胃腺细胞和大鼠皮质膜表现出不同的亲和力，提示胃胃泌素受体（任意称为CCK-B1受体）与先前假设的与CCK中枢受体（称为CCK-B2）的关系不那么紧密。该系列中最有效的化合物，即（R）-4-（3,5-dichlorobenzamido）-5-（8-azaspiro [4.5] d

  DOI：

  10.1021/jm00079a003

文献信息

• Structure−Antigastrin Activity Relationships of New Spiroglumide Amido Acid Derivatives
  作者：Francesco Makovec、Walter Peris、Sandra Frigerio、Roberto Giovanetti、Ornella Letari、Laura Mennuni、Laura Revel

  DOI：10.1021/jm950372w

  日期：1996.1.1

  A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbit gastric parietal cells. Appropriate chemical manipulations of the structure of spiroglumide (CR 2194), i.e., (R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro[4,5]decan-8-yl)-5-oxopentanoic acid, led to potent and selective antagonists of CCKB/gastrin receptors. Structure-activity relationships are discussed. Some of these new derivatives, as, for example, compound 54 (CR 2622), i.e., (S)-4-[[(R)-4'-[(3,5-dichlorobenzoyl)amino]-5'-(8-azaspiro[4.5] decan-8-yl)-5'-oxo-pentanonyl]amino]-5-(1-naphthylamino)-5- oxopentanoic acid, exhibit activity 70-170 times greater than that of spiroglumide, depending upon the model used (IC50 = 2 x 10(-8) vs 140 x 10(-8) mol in binding inhibition of [H-3]-N-Me-N-Leu-CCK-8 in guinea pig brain cortex and IC50 = 0.7 x 10(-8) vs 122.3 x 10(-8) mol in inhibition of gastrin-induced Ca2+ mobilization in parietal cells of rabbit, respectively). Computer-assisted conformational analysis studies were carried out in order to compare the chemical structure of both the agonist (pentagastrin) and the antagonist (54).
• Structure-antigastrin activity relationships of new (R)-4-benzamido-5-oxopentanoic acid derivatives
  作者：Francesco Makovec、Walter Peris、Laura Revel、Roberto Giovanetti、Laura Mennuni、Lucio C. Rovati

  DOI：10.1021/jm00079a003

  日期：1992.1

  CCK-B1 receptor) is not as closely related to the CCK central receptor (termed CCK-B2) as previously hypothesized. The antigastric activity of the most potent compound of the series, i.e. (R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro[4.5]decan- 8-yl)-5-oxopentanoic acid (compound 28, CR 2194) was further evaluated in vivo: in the first hour after administration the compound inhibits acid secretion induced

  通过立体保守方法合成了新的（R）-4-benzamido-5-oxopentanoic酸衍生物，并在体外评估了其抑制[125I]（BH）-CCK-8与任一大鼠外周血（CCK-A）结合的能力）或中枢（CCK-B）CCK受体，或[3H] pentagastrin与兔胃腺的结合，以及在体内抑制五肽胃泌素在灌注的大鼠胃中输注所诱导的酸分泌。该系列的母体化合物（洛格米特）是CCK-A受体的第一种非肽类，有效和选择性拮抗剂。化学处理洛格鲁胺的结构导致发现CCK-B /胃泌素受体的选择性拮抗剂。讨论了构效关系。其中一些新衍生物与兔胃腺细胞和大鼠皮质膜表现出不同的亲和力，提示胃胃泌素受体（任意称为CCK-B1受体）与先前假设的与CCK中枢受体（称为CCK-B2）的关系不那么紧密。该系列中最有效的化合物，即（R）-4-（3,5-dichlorobenzamido）-5-（8-azaspiro [4.5] d