α-<3<<(1,1-dimethylethoxy)carbonyl>amino>-1(E)-propenyl>benzenepropanoic acid | 134161-23-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: α-<3<<(1,1-dimethylethoxy)carbonyl>amino>-1(E)-propenyl>benzenepropanoic acid
• 英文别名: (2RS,3E)-5-t-butoxycarbonylamino-2-benzylpent-3-enoic acid；(E)-2-benzyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]pent-3-enoic acid
• CAS: 134161-23-2
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: UHWRBBGPHKQDLH-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-<3<<(1,1-dimethylethoxy)carbonyl>amino>-1(E)-propenyl>benzenepropanoic acid 在 N-甲基吗啉 、 盐酸 、 碘 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.33h， 生成 methyl 13α-<<(1,1-dimethylethoxy)carbonyl>amino>-3,3-14,14-tetramethyl-6,12-dioxo-7-(phenylmethyl)-1,2-dithia-5,11-diazacyclotetradec-8-ene-(4R)-4α-carboxylate
  参考文献：
  名称：

  Analogs of the .delta. opioid receptor selective cyclic peptide [cyclic][2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions

  摘要：

  In order to develop systemically-active opioid peptides, the delta-selective, opioid pentapeptide [D-Pen2,D-Pen5]-enkephalin (DPDPE) was modified by esterification and by substitution of 2,6-dimethyltyrosine for tyrosine to yield 4. Compound 4 was on the order of 8- and 800-fold more active than DPDPE in both delta and mu-opioid radioligand binding assays, respectively, in rat neural membrane suspensions. Compound 4 was considerably more potent than DPDPE at inhibiting contractions of electrically-stimulated mouse vas deferens in vitro, and this effect was very sensitive to naltrindole, a delta-selective opioid antagonist. These observations can be taken as indication that 4 exerts its effects through delta-opioid receptors. This interpretation is supported by the finding that the EC50 value of 4 derived in the smooth muscle assay is very similar to that derived in NG108-15 neuroblastoma cells, a preparation devoid of mu-receptors. Unlike DPDPE, 4 exhibited significant, naloxone-sensitive, antinociceptive activity when administered systemically, as measured by inhibition of phenylbenzquinone-induced stretching in mice (ED50 = 2.1 mg/kg). Compound 4 also displayed significant antinociceptive activity following systemic administration as measured by its action in mice to increase latencies for tail withdrawal from radiant heat (ED50 = 50 mg/kg). Compound 4 did not produce morphine-like discriminative stimulus effects in rats trained to discriminate 3.0 mg/kg morphine from vehicle at doses ranging from 30 to 120 mg/kg. This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects. Physical dependence, however, could be induced in mice at higher doses of 4 under a progressively-graded, 4-day dose regimen. Congeners of 4 with amide bond surrogates for the Gly-Phe amide bond (oxymethylene, trans-double bond, and bismethylene isosteres) in the cyclic core of DPDPE were prepared in an attempt to increase the antinociceptive activity of 4. While some of the were active in the in vitro assays, they did not display significant antinociceptive activity following systemic administration. The preparation of all the compounds was accomplished by solution-phase methods. The which might underlie the biological and systemic activity of 4 are discussed.

  DOI：

  10.1021/jm00094a002
• 作为产物：
  描述：

  3-苯丙酸乙酯 在 palladium on activated charcoal chromium(VI) oxide 、 4-二甲氨基吡啶 、 sodium hydroxide 、 硫酸 、 氢气 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 二异丁基氢化铝 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 氯仿 、 丙酮 、 甲苯 、 xylene 为溶剂， -78.0~25.0 ℃ 、34.48 kPa 条件下， 反应 77.0h， 生成 α-<3<<(1,1-dimethylethoxy)carbonyl>amino>-1(E)-propenyl>benzenepropanoic acid
  参考文献：
  名称：

  Analogs of the .delta. opioid receptor selective cyclic peptide [cyclic][2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions

  摘要：

  In order to develop systemically-active opioid peptides, the delta-selective, opioid pentapeptide [D-Pen2,D-Pen5]-enkephalin (DPDPE) was modified by esterification and by substitution of 2,6-dimethyltyrosine for tyrosine to yield 4. Compound 4 was on the order of 8- and 800-fold more active than DPDPE in both delta and mu-opioid radioligand binding assays, respectively, in rat neural membrane suspensions. Compound 4 was considerably more potent than DPDPE at inhibiting contractions of electrically-stimulated mouse vas deferens in vitro, and this effect was very sensitive to naltrindole, a delta-selective opioid antagonist. These observations can be taken as indication that 4 exerts its effects through delta-opioid receptors. This interpretation is supported by the finding that the EC50 value of 4 derived in the smooth muscle assay is very similar to that derived in NG108-15 neuroblastoma cells, a preparation devoid of mu-receptors. Unlike DPDPE, 4 exhibited significant, naloxone-sensitive, antinociceptive activity when administered systemically, as measured by inhibition of phenylbenzquinone-induced stretching in mice (ED50 = 2.1 mg/kg). Compound 4 also displayed significant antinociceptive activity following systemic administration as measured by its action in mice to increase latencies for tail withdrawal from radiant heat (ED50 = 50 mg/kg). Compound 4 did not produce morphine-like discriminative stimulus effects in rats trained to discriminate 3.0 mg/kg morphine from vehicle at doses ranging from 30 to 120 mg/kg. This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects. Physical dependence, however, could be induced in mice at higher doses of 4 under a progressively-graded, 4-day dose regimen. Congeners of 4 with amide bond surrogates for the Gly-Phe amide bond (oxymethylene, trans-double bond, and bismethylene isosteres) in the cyclic core of DPDPE were prepared in an attempt to increase the antinociceptive activity of 4. While some of the were active in the in vitro assays, they did not display significant antinociceptive activity following systemic administration. The preparation of all the compounds was accomplished by solution-phase methods. The which might underlie the biological and systemic activity of 4 are discussed.

  DOI：

  10.1021/jm00094a002

文献信息

• Scarso, A.; Degelaen, J.; Viville, R., Bulletin des Societes Chimiques Belges, 1991, vol. 100, # 5, p. 381 - 399
  作者：Scarso, A.、Degelaen, J.、Viville, R.、Cock, E. De、Marsenille, M. Van、et al.

  DOI：——

  日期：——
• PSEUDO- AND NON-PEPTIDE BRADYKININ RECEPTOR ANTAGONISTS
  申请人：SCIOS NOVA INC.

  公开号：EP0716661A1

  公开（公告）日：1996-06-19
• US5552383A
  申请人：——

  公开号：US5552383A

  公开（公告）日：1996-09-03
• US5686565A
  申请人：——

  公开号：US5686565A

  公开（公告）日：1997-11-11
• US5817756A
  申请人：——

  公开号：US5817756A

  公开（公告）日：1998-10-06