S-苄基-L-半胱氨酸砜 | 25644-88-6

• 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: S-苄基-L-半胱氨酸砜
• 英文名称: S-Benzyl-L-cystein-sulfon
• 英文别名: (2R)-2-azaniumyl-3-benzylsulfonylpropanoate
• CAS: 25644-88-6
• 化学式: C₁₀H₁₃NO₄S
• 分子量: 243.284
• InChiKey: KDIYEJQJSZCWGR-VIFPVBQESA-N

物化性质

• 熔点：
  174-176°C
• 沸点：
  519.1±50.0 °C(Predicted)
• 密度：
  1.390±0.06 g/cm3(Predicted)
• 溶解度：
  酸水溶液（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  S-苄基-L-半胱氨酸砜 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 28.0h， 生成 Cbz-Ile-Ala(SO2Bn)-OSu
  参考文献：
  名称：

  Optimization of Subsite Binding to the β5 Subunit of the Human 20S Proteasome Using Vinyl Sulfones and 2-Keto-1,3,4-oxadiazoles:  Syntheses and Cellular Properties of Potent, Selective Proteasome Inhibitors

  摘要：

  Beginning with the peptide sequence Cbz-Ile-Glu(OtBu)-Ala-Leu found in PSI (3), a series of vinyl sulfones (VS) were synthesized for evaluation as inhibitors of the chymotrypsin-like activity of the 20S proteasome. Variations at the key P3 position confirmed the importance of a long side chain capped with a hydrophobic group for optimal potency, consistent with a model of binding to the S3 subsite. The tert-butyl glutamic ester initially used at P3 gave plasma unstable, insoluble compounds and was replaced with the better isostere, N-beta-neopentyl asparagine. The inhibitors were shortened by replacing the N-terminal Cbz-isoleucine with a p-tosyl group without loss of potency. Small L-amino acids were used at P2, where D-substitution was not tolerated. The resulting optimized P4-P3-P2 sequence was grafted onto a novel proteasome inhibitor warhead, 2-keto-1,3,4-oxadiazoles (KOD), to produce reversible, subnanomolar proteasome inhibitors that were 1000-fold selective versus cathepsin B (CatB), cathepsin S (CatS), and trypsin-like as well as PGPH-like proteasome activity. A number of compounds in both the VS and the KOD series exhibited growth inhibitory effects against the human prostate cancer cell line PC3 at submicromolar concentrations.

  DOI：

  10.1021/jm058289o
• 作为产物：
  描述：

  S-苄基-L-半胱氨酸 在 ammonium molybdate 、 高氯酸 、 双氧水 作用下， 生成 S-苄基-L-半胱氨酸砜
  参考文献：
  名称：

  将苄基磺酰基（砜）中间体还原为亚磺酸。牛磺酸，L-半胱氨酸和L-高半胱氨酸亚磺酸的合成

  摘要：

  用金属钠还原液态氨中的半胱胺，L-半胱氨酸和L-同型半胱氨酸的苄基磺酰基衍生物，其相应的亚磺酸收率在80-90％范围内。

  DOI：

  10.1039/j39700000270

文献信息

• Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-X_L and BCL-2
  作者：Michael J. Roy、Amelia Vom、Toru Okamoto、Brian J. Smith、Richard W. Birkinshaw、Hong Yang、Houda Abdo、Christine. A. White、David Segal、David C. S. Huang、Jonathan B. Baell、Peter M. Colman、Peter E. Czabotar、Guillaume Lessene

  DOI：10.1021/acs.jmedchem.0c01771

  日期：2021.5.13

  Here, we outline the crystallography-guided development of a structurally distinct series of BCL-XL/BCL-2 inhibitors based on a benzoylurea scaffold, originally proposed as α-helix mimetics. We describe structure-guided exploration of a cryptic “p5” pocket identified in BCL-XL. This work yields novel inhibitors with submicromolar binding, with marked selectivity toward BCL-XL. Extension into the hydrophobic

  的BCL-2家族蛋白（包括促存活蛋白BCL-2，BCL-X大号和MCL-1）是用于新型抗癌治疗剂的发展的一个重要目标。尽管靶向小分子蛋白质相互作用的挑战，但许多抑制剂（称为BH3模拟物）已进入临床，并且BCL-2抑制剂ABT-199 / venetoclax已经证明具有转化性。对于BCL-X大号，新的验证化工系列是可取的。在这里，我们勾勒出一个结构不同的系列BCL-X的结晶学引导发展大号基于一个苯甲酰脲支架/ BCL-2抑制剂，最初提出如α螺旋模拟物。我们描述了在BCL-X L中识别出的隐秘“ p5”口袋的结构指导探索。这项工作产生了具有亚微摩尔的结合，与朝向BCL-X标记选择性新型抑制剂大号。延伸到疏水P2口袋产生最有效的抑制剂在系列，强烈结合BCL-X大号和BCL-2（纳摩尔范围的半最大抑制浓度（IC 50在工程改造到细胞）），并显示基于机制的杀伤依靠BCL-X L生存。
• Peptides which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, compositions and uses thereof
  申请人：——

  公开号：US20040162239A1

  公开（公告）日：2004-08-19

  The present invention relates generally to peptides, which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, methods of making peptides, which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, pharmaceutical compositions of these peptides and methods of using these peptides and pharmaceutical compositions of these peptides to treat diseases associated with aberrant vascularization.

  本发明一般涉及抑制血管生成、细胞迁移、细胞侵袭和细胞增殖的多肽，抑制血管生成、细胞迁移、细胞侵袭和细胞增殖的多肽的制造方法，这些多肽的药物组合物，以及使用这些多肽和这些多肽的药物组合物治疗与血管异常有关的疾病的方法。
• <b>Oxidative Cleavage of Tyrosyl-Peptide Bonds. III. Synthesis and Cleavage of Peptides Containing Sulfur Moieties</b>
  作者：John G. Wilson、Louis A. Cohen

  DOI：10.1021/ja00888a018

  日期：1963.3
• Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers
  作者：David C. Tully、Hong Liu、Arnab K. Chatterjee、Phil B. Alper、Robert Epple、Jennifer A. Williams、Michael J. Roberts、David H. Woodmansee、Brian T. Masick、Christine Tumanut、Jun Li、Glen Spraggon、Michael Hornsby、Jonathan Chang、Tove Tuntland、Thomas Hollenbeck、Perry Gordon、Jennifer L. Harris、Donald S. Karanewsky

  DOI：10.1016/j.bmcl.2006.07.033

  日期：2006.10

  The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.
• Selenoxidation by Flavin-Containing Monooxygenases as a Novel Pathway for β-Elimination of Selenocysteine <i>Se</i>-Conjugates
  作者：Martijn Rooseboom、Jan N. M. Commandeur、Gerrit C. Floor、Allan E. Rettie、Nico P. E. Vermeulen

  DOI：10.1021/tx0001326

  日期：2001.1.1

  Previously, it was shown that beta -elimination of selenocysteine Se-conjugates by rat renal cytosol leading to pyruvate formation was not solely catalyzed by pyridoxal phosphate-dependent enzymes. It was hypothesized that selenoxidation of the selenocysteine Se-conjugates, followed by syn-elimination, may be an alternative mechanism for pyruvate formation. In this study, selenoxidation of selenocysteine Se-conjugates was studied using rat liver microsomes and recombinant human oxidative enzymes. For all six selenocysteine Se-conjugates that were tested, it was found that rat liver microsomal incubations led to the formation of pyruvate, whereas the corresponding selenoxides were not observed. Microsomal pyruvate formation from Se-benzyl-L-selenocysteine (SeBC) was NADPH-dependent, but only marginally inhibited by several P450 inhibitors. Inhibition by methimazole and by heat pretreatment and stimulation by n-octylamine indicated that flavin-containing monooxygenases are mainly responsible for pyruvate formation from the selenocysteine Se-conjugates in rat liver microsomes. In the case of S-benzyl-L-cysteine, the sulfur analogue of SeBC, pyruvate formation was not observed. For this substrate, a chemically stable sulfoxide could be observed, as previously described. By using recombinantly expressed human flavin-containing monooxygenases and P450 enzymes, it was delineated that SeBC is selenoxidized by human FMOs, but not by human P450s. The k(cat)/K-m of selenoxidation was 3.8-fold higher for FMO-1 than for FMO-3. In conclusion, selenoxidation of selenocysteine Se-conjugates catalyzed by FMOs and subsequently syn-elimination has taken place as an alternative route for the formation of pyruvate from selenocysteine Se-conjugates. Although selenoxides are known to be easily reduced by thiol compounds, microsomal pyruvate formation from SeBC was only 75% inhibited in the presence of an excess of glutathione. This indicates that even in the presence of physiological concentrations of reducing thiol compounds, selenoxides of selenocysteine Se-conjugates may undergo syn-elimination to some extent. Whether selenoxides and/or selenenic acids that are formed are involved in the activity of chemopreventive selenocysteine Se-conjugates remains to be established.