N,O-ditosylhydroxy-L-proline | 5260-29-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,O-ditosylhydroxy-L-proline
• 英文别名: 1-(toluene-4-sulfonyl)-4c-(toluene-4-sulfonyloxy)-(2rH)-L-proline；trans-4-p-Toluolsulfonyloxy-N-p-toluolsulfonyl-prolin；N,O-Ditosyl-trans-4-hydroxy-L-prolin；N,O-Di-p-tosylhydroxy-L-prolin；(2S,4R)-1-(4-methylphenyl)sulfonyl-4-(4-methylphenyl)sulfonyloxypyrrolidine-2-carboxylic acid
• CAS: 5260-29-7
• 化学式: C₁₉H₂₁NO₇S₂
• 分子量: 439.51
• InChiKey: BLMFLUPREFKLIJ-QAPCUYQASA-N

物化性质

• 沸点：
  656.4±65.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,O-ditosylhydroxy-L-proline 在 sodium tetrahydroborate 、 三氟化硼乙醚 作用下， 以 四氢呋喃 为溶剂， 以85%的产率得到(2S,4R)-2-(hydroxymethyl)-1-(toluene-4-sulfonyl)-4-(toluene-4-sulfonyloxy)pyrrolidine
  参考文献：
  名称：

  Chemoenzymatic synthesis and cannabinoid activity of a new diazabicyclic amide of phenylacetylricinoleic acid

  摘要：

  Endocannabinoids (eCBs) are endogenous neuromodulators of synaptic transmission. Their dysfunction may cause debilitating disorders of diverse clinical manifestation. For example, drug addiction, lack of sex desire, eating disorders, such as anorexia or bulimia and dyssomnias. eCBs also participate in the regulation of core temperature and pain perception. In this context, it is important to recognize the utility of cannabinoid receptor 1 (CB1R) agonists, natural as Delta(9)-tetrahydrocannabinol (THC) or synthetic as Nabilone as useful drugs to alleviate this kind of patients' suffering. Therefore, we have developed a new drug, (R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-yl phenylacetate (PhAR-DBH-Me), that appears to bind and activate the CB1R. This diazabicyclic amide was synthesized from phenylacetylricinoleic acid and (1S, 4S)-2,5-diazabicyclo[ 2.2.1] heptane. To test its cannabinergic properties we evaluated its effects on core temperature, pain perception, and the sleep-waking cycle of rats. Results indicate that 20 and 40 mg/kg of PhAR-DBH-Me readily reduced core temperature and increased pain perception threshold. In addition, 20 mg/kg increased REM sleep in otherwise normal rats. All these effects were prevented or attenuated by AM251, a CB1R antagonist. Place preference conditioning studies indicated that this molecule does not produce rewarding effects. These results strongly support that PhAR-DBH-Me possesses cannabinoid activity without the reinforcement effects. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.074
• 作为产物：
  描述：

  对甲苯磺酰氯 、 L-羟基脯氨酸 在 sodium carbonate 作用下， 以 水 为溶剂， 以94%的产率得到N,O-ditosylhydroxy-L-proline
  参考文献：
  名称：

  Chemoenzymatic synthesis and cannabinoid activity of a new diazabicyclic amide of phenylacetylricinoleic acid

  摘要：

  Endocannabinoids (eCBs) are endogenous neuromodulators of synaptic transmission. Their dysfunction may cause debilitating disorders of diverse clinical manifestation. For example, drug addiction, lack of sex desire, eating disorders, such as anorexia or bulimia and dyssomnias. eCBs also participate in the regulation of core temperature and pain perception. In this context, it is important to recognize the utility of cannabinoid receptor 1 (CB1R) agonists, natural as Delta(9)-tetrahydrocannabinol (THC) or synthetic as Nabilone as useful drugs to alleviate this kind of patients' suffering. Therefore, we have developed a new drug, (R,Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-yl phenylacetate (PhAR-DBH-Me), that appears to bind and activate the CB1R. This diazabicyclic amide was synthesized from phenylacetylricinoleic acid and (1S, 4S)-2,5-diazabicyclo[ 2.2.1] heptane. To test its cannabinergic properties we evaluated its effects on core temperature, pain perception, and the sleep-waking cycle of rats. Results indicate that 20 and 40 mg/kg of PhAR-DBH-Me readily reduced core temperature and increased pain perception threshold. In addition, 20 mg/kg increased REM sleep in otherwise normal rats. All these effects were prevented or attenuated by AM251, a CB1R antagonist. Place preference conditioning studies indicated that this molecule does not produce rewarding effects. These results strongly support that PhAR-DBH-Me possesses cannabinoid activity without the reinforcement effects. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.074

文献信息

• Azido, imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids having hypotensive activity
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0042639A2

  公开（公告）日：1981-12-30

  Azido, imido, amido and amino derivatives of mercap- toacyl prolines and pipecolic acids having the formula wherein -NR1-R2 is azido or R1 and R2 are the same or different and are hydrogen, alkyl, cycloalkyl, 1-adamantyl, aryl, arylalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, or arylvinylcarbonyl, or together with the nitrogen atom to which they are attached R, and R2 are 1-pyrrolidinyl, 1-piperidinyl, 1-homopiperidinyl, 4-morpholinyl, 4-alkyl-1-piperazinyl, 4-aryl-1-piperazinyl, 1-imidazolyl, 1-pyrrolidinyl-2,5-dione, 3-alkyl-1-pyrrolidinyl-2,5-dione, 3-aryl-1-pyrrolidinyl-2,5-dione, 1-piperidinyl-2,6-dione,3-alkyl-1- piperidinyl-2,6-dione, 3-aryl-1-piperidinyl,2-6-dione, 2H-isoindol-2-yl-1,3-dione, hexahydro-2H-isoindol-2-yl-1,3-dione, 2,5-dihydro-2,5-dioxo-lH-pyrrol-1-yl, 1,1,3- trioxo-1,2-benzisothiazol-2(3H)-yl, or 1,3-dihydro-1,3-dioxo-2H-benz[de]isoquinolin-2-yl; R3 is hydrogen, alkyl, aryl, arylalkyl, or a hydrolyzable acyl protecting group; R4 is hydrogen, alkyl, alkylthio, or trifluoromethyl; Rs is hydrogen, alkyl, or arylalkyl; n is 0, 1 or 2; and p is 1 or 2; or a salt thereof, or symmetrical dimer thereof are useful for the treatment of hypertension.

  巯基脯氨酸和哌啶醇酸的叠氮、亚胺、酰胺和氨基衍生物，其式为 其中 -NR1-R2 为叠氮基，或 R1 和 R2 相同或不同，且为氢、烷基、环烷基、1-金刚烷基、芳基、芳烷基、烷基羰基、芳基羰基、芳基烷基羰基、烷基磺酰基、芳基磺酰基、芳基乙烯基羰基或芳基乙烯基羰基、或芳基乙烯基羰基，或连同所连接的氮原子 R 和 R2 是 1-吡咯烷基、1-哌啶基、1-高哌啶基、4-吗啉基、4-烷基-1-哌嗪基、4-芳基-1-哌嗪基1-咪唑基、1-吡咯烷基-2,5-二酮、3-烷基-1-吡咯烷基-2,5-二酮、3-芳基-1-吡咯烷基-2,5-二酮、1-哌啶基-2,6-二酮、3-烷基-1-哌啶基-2,6-二酮、3-芳基-1-哌啶基 2-6-二酮、2H-isoindol-2-yl-1,3-dione, hexahydro-2H-isoindol-2-yl-1,3-dione, 2,5-dihydro-2,5-dioxo-lH-pyrrol-1-yl, 1,1,3- trioxo-1,2-benzisothiazol-2(3H)-yl, or 1,3-dihydro-1,3-dioxo-2H-benz[de]isoquinolin-2-yl; R3 是氢、烷基、芳基、芳烷基或可水解的酰基保护基团； R4 是氢、烷基、烷硫基或三氟甲基； Rs 是氢、烷基或芳烷基； n 是 0、1 或 2；以及 p 为 1 或 2； 或其盐，或其对称二聚体可用于治疗高血压。
• Portoghese,P.S.; Sepp,D.T., Journal of Heterocyclic Chemistry, 1971, vol. 8, p. 531 - 535
  作者：Portoghese,P.S.、Sepp,D.T.

  DOI：——

  日期：——
• Bowers-Nemia, Margaret M.; Joullie, Madeleine M., Heterocycles, 1983, vol. 20, # 5, p. 817 - 828
  作者：Bowers-Nemia, Margaret M.、Joullie, Madeleine M.

  DOI：——

  日期：——
• BRAISH, TAMIM F.;FOX, DARRELL E., J. ORG. CHEM., 55,(1990) N, C. 1684-1687
  作者：BRAISH, TAMIM F.、FOX, DARRELL E.

  DOI：——

  日期：——
• US4310461A
  申请人：——

  公开号：US4310461A

  公开（公告）日：1982-01-12