Boc-S-4-甲基苄基-L-青霉胺 | 104323-41-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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
• 中文名称: Boc-S-4-甲基苄基-L-青霉胺
• 英文名称: N^α-Boc-L-Pen(S-4'-methylbenzyl)
• 英文别名: N^α-Boc-Pen(S-4-MeBzl)；Boc-L-4-Methylbenzyl-L-Penicillamine；(2R)-3-methyl-3-[(4-methylphenyl)methylsulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 104323-41-3
• 化学式: C₁₈H₂₇NO₄S
• 分子量: 353.483
• InChiKey: SIBYHJVDFRKDDV-CQSZACIVSA-N

物化性质

• 沸点：
  504.2±50.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-S-4-甲基苄基-L-青霉胺 在 ammonium acetate 、 potassium hexacyanoferrate(III) 作用下， 反应 1.0h， 生成 D-Phe-cyclo[Cys-Tyr-D-Trp-Arg-Thr-Pen]-Thr-NH2
  参考文献：
  名称：

  Design and synthesis of conformationally constrained somatostatin analogs with high potency and specificity for .mu. opioid receptors

  摘要：

  A series of cyclic, conformationally constrained peptides related to somatostatin were designed and synthesized in an effort to develop highly selective and potent peptides for the mu opioid receptor. The following new peptides were prepared and tested for their mu opioid receptor potency and selectively in rat brain binding assays: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (2, CTOP); D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (3, CTAP); D-Phe-Cys-Tyr-D-Trp-Nle-Thr-Pen-Thr-NH2 (4); D-Phe-Cys-Tyr-D-Trp-Lys-Val-Pen-Thr-NH2 (5); D-Phe-Cys-Tyr-D-Trp-Lys-Gly-Pen-Thr-NH2 (6); D-Phe-Cys-Tyr-Trp-Lys-Thr-Pen-Thr-NH2 (7); D-Tyr-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH (8); D-PhGly-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (9); and D-PhGly-Pen-Phe-D-Trp-Lys-Thr-Cys-Thr-OH (10). The most selective peptide, 2 (CTOP), displayed both high affinity (IC50 = 3.5 nM) and exceptional selectivity (IC50 delta/IC50 mu = 4,000) for mu opioid receptors. Furthermore, 2 exhibited very low affinity for somatostatin receptors in the rat brain (IC50 greater than 24,000 nM), with an IC50 somatostatin/IC50 mu receptor selectivity of 8,750. These conformationally constrained cyclic peptides should provide new insight into the structural and conformational requirements for the mu opioid receptor and the physiological role of this receptor.

  DOI：

  10.1021/jm00161a037

文献信息

• A new approach to receptor ligand design: synthesis and conformation of a new class of potent and highly selective μ opioid antagonists utilizing tetrahydroisoouinoline carroxylic acid
  作者：Wieslaw Kazmierski、Victor J. Hruby

  DOI：10.1016/s0040-4020(01)86110-x

  日期：1988.1

  describe a new class of potent and selective μ opioid receptor antagonists and demonstrate a new approach for the design of receptor specific ligands by which a low affinity, “non-physiological” activity of a natural peptide hormone is converted to a high potency, receptor selective ligand for that receptor, and, at the same time, eliminates the activity at the natural receptors for the peptide.

  对阿片受体（μ，δ，κ等）的生理功能的研究需要有效和选择性的受体配体。构象约束提供了增加柔性肽的受体选择性的有用方法。这种方法减少了配体可访问的低能构象集，因此可以提供对可能对特定受体亚型具有高亲和力的拓扑学特征的洞察力。使用这种方法，我们描述了一类新型的有效和选择性μ阿片受体拮抗剂，并展示了一种设计受体特异性配体的新方法，该方法可将天然肽激素的低亲和力，“非生理”活性转化为高效的受体选择性配体，同时，
• Fluoropyrrolidines as dipeptidyl peptidase inhibitors
  申请人：——

  公开号：US20040171848A1

  公开（公告）日：2004-09-02

  The present invention relates to novel compounds, their use for inhibiting serine proteases, such as dipeptidyl peptidases, such as dipeptidyl peptidase IV (DPP-IV) and to methods for their production and their therapeutic utility.

  本发明涉及新型化合物，其用于抑制丝氨酸蛋白酶，例如二肽基肽酶，例如二肽基肽酶IV（DPP-IV），以及其生产方法和治疗效用。
• Opiate Aromatic Pharmacophore Structure−Activity Relationships in CTAP Analogues Determined by Topographical Bias, Two-Dimensional NMR, and Biological Activity Assays
  作者：G. Gregg Bonner、Peg Davis、Dagmar Stropova、Sidney Edsall、Henry I. Yamamura、Frank Porreca、Victor J. Hruby

  DOI：10.1021/jm9900218

  日期：2000.2.1

  Topographically constrained analogues of the highly mu-opioid-receptor-selective antagonist CTAP (H-D-Phe-c[Cys-Tyr-D-Trp-Arg-Thr-Pen]-Thr-NH2, 1) were prepared by solid-phase peptide synthesis. Replacement of the D-Phe residue with conformationally biased beta-methyl derivatives of phenylalanine or tryptophan (2R,3R; 2R,3S; 2S,3R; 2S,3S) yielded peptides that displayed widely varying types of biological activities. In an effort to correlate the observed biological activities of these analogues with their structures, two-dimensional H-1 NMR and molecular modeling was performed. Unlike the parent (1), which is essentially a pure mu antagonist with weak delta agonist activities in the MVD bioassay, the diastereomeric beta-MePhe(1)-containing peptides exhibited simultaneous delta agonism and mu antagonism by the (2R,3R)-containing isomer 2; mu antagonism by the (2R,3S)-containing isomer 3; weak mu agonism by the (2S,3R)-containing isomer 4; and delta agonism by the (2S,3S)-containing isomer 5. Incorporation of beta-MeTrp isomers into position 1 led to peptides that were mu antagonists (2R,3R), 8; (2R,3S), 9, or essentially inactive (<10%) in the MVD and GPI assays (2S,3R), 10; (2S,3S), 11. Interestingly, in vivo antinociceptive activity was predicted by neither MVD nor GPI bioactivity. When D-Trp was incorporated in position 1, the result (7) is a partial, yet relatively potent mu agonist which also displayed weak delta agonist activity. Molecular modeling based on 2D NMR revealed that low energy conformers of peptides with similar biological activities had similar aromatic pharmacophore orientations and interaromatic distances. Peptides that exhibit mu antagonism have interaromatic distances of 7.0-7.9 Angstrom and have their amino terminal aromatic moiety pointing in a direction opposite to the direction that the amino terminus points. Peptides with delta opioid activity displayed an interaromatic distance of <7 Angstrom and had their amino terminal aromatic moiety pointing in the same direction as the amino terminus.
• Amide bond surrogates: pseudopeptides and macrocycles
  作者：Arno F. Spatola、Krzysztof Darlak

  DOI：10.1016/s0040-4020(01)86119-6

  日期：1988.1
• Design, Synthesis, and Biological Properties of highly Potent Cyclic Dynorphin A Analogs. Analogs Cyclized between Positions 5 and 11
  作者：Jean-Philippe Meyer、Nathan Collins、Feng-Di Lung、Peg Davis、Teresa Zalewska、Frank Porreca、Henry I. Yamamura、Victor J. Hruby

  DOI：10.1021/jm00049a010

  日期：1994.11

  We have recently reported the synthesis of several cyclic disulfide bridge-containing peptide analogues of dynorphin A (Dyn A), which were conformationally constrained in the putative address segment of the opioid ligand. Several of these analogues, bridged between positions 5 and 11 of Dyn A(1-11)-NH2, exhibited unexpected selectivities for the kappa and mu receptors of the central over the peripheral nervous systems. In order to further investigate the conformational and topographical requirements for the residues in positions 5 and 11 of these analogues, we have synthesized a systematic series of Dyn A(1-11)-NH2 analogues incorporating the sulfydryl containing amino acids L- and D-Cys and L- and D-Pen in positions 5 and 11, thus producing 16 cyclic peptides. In addition, Dyn A(1-11)-NH2, [D-Leu(5)]Dyn A(1-11)-NH2, and [D-Lys(11)]Dyn A(1-11)-NH2 were synthesized as standards. Several of these cyclic analogues, especially c[Cys(5), D-Cys(11)] Dyn A(1-11)-NH2, c[Cys(5), L- or D-Pen(11)]Dyn A(1-11)-NH2, c[Pen(5), L-Pen(11)]Dyn A(1-11)-NH2 and c[Pen(5), L- or D-Cys(11)]Dyn A(1-11)-NH2, retained the same affinity and selectivity (vs the mu and delta receptors) as the parent compound Dyn A(1-11)-NH2 in the guinea pig brain (GPB). These same analogues and most others exhibited a much lower activity in the guinea pig ileum (GPI), thus leading to centrally vs peripherally selective peptides, but showed a different structure-activity relationship than found previously. In a wider scope, this series of analogues also provided new insights into which amino acids (and their configurations) may be used in positions 5 and 11 of Dyn A analogues for high potency and good selectivity at kappa opioid receptors. The results obtained in the GPB suggest that requirements for binding are not the same for the kappa, mu, or delta central receptors.