Boc-S-三苯甲游基-D-青霉胺 | 135592-14-2

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: Boc-S-三苯甲游基-D-青霉胺
• 中文别名: BOC-S-三苯甲游基-D-青霉胺
• 英文名称: N-Boc-S-trityl-D-Pen-OH
• 英文别名: Boc-S-trityl-D-penicillamine；(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylbutanoic acid
• CAS: 135592-14-2
• 化学式: C₂₉H₃₃NO₄S
• 分子量: 491.651
• InChiKey: GFULWLRDJMLHCD-DEOSSOPVSA-N

物化性质

• 沸点：
  621.0±55.0 °C(Predicted)
• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  Boc-S-三苯甲游基-D-青霉胺 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 50.33h， 生成 methyl 13α-<<2(S)-amino-3-(4-hydroxy-2,6-dimethylphenyl)-1-oxopropyl>amino>-3,3,14,14-tetramethyl-6,12-dioxo-7-(phenylmethyl)-1,2-dithia-5,11-diazacyclotetradecane-(4R)-4α-carboxylate hydrochloride
  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

• Tetrahydroimidazo[1,2‐ <i>a</i> ]pyrazine Derivatives: Synthesis and Evaluation as Gα _q ‐Protein Ligands
  作者：Jim Küppers、Tobias Benkel、Suvi Annala、Kenichi Kimura、Lisa Reinelt、Bernd K. Fleischmann、Evi Kostenis、Michael Gütschow

  DOI：10.1002/chem.202001446

  日期：2020.10

  The 5,6,7,8‐tetrahydroimidazo[1,2‐a]pyrazine derivative BIM‐46174 and its dimeric form BIM‐46187 (1) are heterocyclized dipeptides that belong to the very few cell‐permeable compounds known to preferentially silence Gαq proteins. To explore the chemical space of Gαq inhibitors of the BIM chemotype, a combinatorial approach was conducted towards a library of BIM molecules. This library was evaluated

  5,6,7,8-四氢咪唑并[1,2- a ]吡嗪衍生物 BIM-46174 及其二聚体形式 BIM-46187 ( 1 ) 是杂环化二肽，属于极少数已知优先沉默 Gα 的细胞渗透性化合物q蛋白。为了探索 BIM 化学型 Gα q抑制剂的化学空间，对 BIM 分子库进行了组合方法。该文库在基于第二信使的荧光测定中进行了评估，通过测定细胞内肌醇1-磷酸来分析 Gα q蛋白的活性。推导了结构-活性关系并获得了生物活性的结构要求，它们是（i）氧化还原反应性硫醇/二硫烷子结构，（ii）N-末端碱性氨基，（iii）环己基丙氨酸部分，和（iv）双环骨架。活性化合物表现出细胞毒性，对此原型抑制剂进行了详细研究1。该化合物以 Gα q/11独立的方式影响结构细胞骨架动力学。
• Nitrosothiol derivatives and their use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05116861A1

  公开（公告）日：1992-05-26

  Novel nitrosothiol derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently a hydrogen atom or a hydrocarbon residue which may be substituted; R.sup.3 is a hydrogen atom, an acyl group or a hydrocarbon residue which may be substituted; X.sup.1 is a hydrogen atom, an acyl group, a lower alkoxy group or a hydrocarbon residue which may be substituted; X.sup.2 is an acyl group or a carboxyl group which may be esterified or which may form an amide; with proviso that when X.sup.2 is a carboxyl group X.sup.1 is not a hydrogen atom or acetyl group and that when both R.sup.1 and R.sup.2 are hydrogen atoms X.sup.1 is not acetyl group or .gamma.-glutamyl group, and salts thereof, show excellent hypotensive action, antiarrhythmic action, anti-anginal action, cardiotonic action or coronary vasodilation, thus being useful as therapeutic or prophylactic agents for the cardiovascular diseases such as hypertension and angina pectoris.

  化合物的名称为Novel nitrosothiol derivatives，其化学式为：##STR1## 其中R1和R2分别为氢原子或可被取代的碳氢残基；R3为氢原子、酰基或可被取代的碳氢残基；X1为氢原子、酰基、低级烷氧基或可被取代的碳氢残基；X2为酰基或可酯化的羧基或可形成酰胺基的羧基；但当X2为羧基时，X1不为氢原子或乙酰基，并且当R1和R2均为氢原子时，X1不为乙酰基或γ-谷氨酰基。该化合物及其盐具有出色的降压作用、抗心律失常作用、抗心绞痛作用、心脏强心作用或冠状动脉扩张作用，因此可作为治疗或预防高血压和心绞痛等心血管疾病的药物。
• Nitrosothiol derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0412699B1

  公开（公告）日：1994-04-27
• US5116861A
  申请人：——

  公开号：US5116861A

  公开（公告）日：1992-05-26
• 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
  作者：Nizal S. Chandrakumar、Awilda Stapelfeld、Patrick M. Beardsley、Oscar T. Lopez、Bridget Drury、Elizabeth Anthony、Michael A. Savage、L. Neil Williamson、Melvin Reichman

  DOI：10.1021/jm00094a002

  日期：1992.8

  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.