N-叔丁氧羰基-S-(4-甲氧基苄基)-D-半胱氨酸 | 58290-35-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 半胱氨酸类衍生物
• 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: N-叔丁氧羰基-S-(4-甲氧基苄基)-D-半胱氨酸
• 英文名称: N-tert-butyloxycarbonyl-S-p-methoxybenzyl-D-cysteine
• 英文别名: N-Boc-D-S-(p-methoxybenzyl)cysteine；N-Boc-S-p-methoxybenzyl-D-cysteine；Boc-DCys(S-p-Mob)；Boc-D-Cys(MBzl)；Boc-S-4-methoxybenzyl-D-cysteine；(2S)-3-[(4-methoxyphenyl)methylsulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 58290-35-0
• 化学式: C₁₆H₂₃NO₅S
• 分子量: 341.428
• InChiKey: VRTXRNJMNFVTOM-CYBMUJFWSA-N

物化性质

• 沸点：
  514.0±50.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-S-(4-甲氧基苄基)-D-半胱氨酸 在 Hg(II) trifluoroacetate 、 硫化氢 、 sodium hydride 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 生成 Benzyloxycarbonylamino-thioacetic acid S-[(S)-2-tert-butoxycarbonylamino-3-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-3-oxo-propyl] ester
  参考文献：
  名称：

  A formal synthesis of althiomycin

  摘要：

  A formal synthesis of the antibiotic althiomycin has been completed preliminary to studies of the interaction of this compound with prokaryotic ribosomes. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00270-3

文献信息

• Amino acid derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04146611A1

  公开（公告）日：1979-03-27

  A method for alleviating or reducing angiotensin related hypertension in hypertensive mammals comprises administering an effective amount of a compound having the general formula ##STR1## Intermediates for the preparation of such compounds are also included.

  一种缓解或减轻高血压哺乳动物中与肾素-血管紧张素相关的高血压的方法，包括给予一种具有一般式##STR1##的化合物的有效量。还包括用于制备这种化合物的中间体。
• Amino mercapto substituted acylamino acids
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04154946A1

  公开（公告）日：1979-05-15

  New substituted acyl derivatives of amino acids which have the general formula ##STR1## are useful as angiotensin converting enzyme inhibitors.

  新的取代基氨基酸酰衍生物具有一般式##STR1##，可用作血管紧张素转化酶抑制剂。
• Method for alleviating hypertension
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04177277A1

  公开（公告）日：1979-12-04

  A method for alleviating or reducing angiotensin related hypertension in hypertensive mammals comprises administering an effective amount of a compound having the general formula ##STR1## Intermediates for the preparation of such compounds are also included.

  一种缓解或减轻高血压哺乳动物中的血管紧张素相关性高血压的方法，包括给予一定剂量的一种具有以下一般式的化合物：##STR1## 也包括用于制备这种化合物的中间体。
• Design of Potent Dicyclic (1−5/4−10) Gonadotropin Releasing Hormone (GnRH) Antagonists
  作者：Jean E. Rivier、Guangcheng Jiang、R. Scott Struthers、Steven C. Koerber、John Porter、Laura A. Cervini、Dean A. Kirby、A. Grey Craig、Catherine L. Rivier

  DOI：10.1021/jm990116+

  日期：2000.3.1

  In three earlier papers, the structures and biological potencies of numerous mono- and dicyclic antagonists of GnRH were reported. Among these, two families, each containing two to four members were identified that had very high antagonist potencies in an antiovulatory assay (within a factor of 2 of those of the most potent linear analogues) and high affinities (K-i < 0.5 nM) for the rat GnRH receptor (rGnRHR). The most favored cycles bridged the side chains of residues (4-10),(1,2) (5-8),(2) (4-10/5-8),(2) (1-3),(3) and (1-3/4-10).(3) Our goal was to identify a consensus model of bioactive conformations of GnRH antagonists, yet these biocompatible constraints did not sufficiently restrain the spatial location of the N-terminal tripeptide with respect to the C-terminal heptapeptide, due largely to the rotational freedom about the bonds connecting these regions. Examination of models derived from NMR studies of cyclo(4-10) analogues suggested a large number of possible cyclic constraints such as cycle (0-8), (1-8), or (2-8). All analogues tested with these substitutions were inactive as antiovulatory agents at 1 mg/rat (5-9) and had low affinity for rGnRHR. On the other hand, bridging positions 3 and 8 with a [DAsp(3)] to [Dbu(8)] (12, K-i = 13 nM) or [Orn(8)] (13, K-i = 14 nM) in the parent compound cyclo(3-8)[Ac-DNal(1),DCpa(2),DXaa(3),Arg(5),DNal(6),Xbb(8),DAla(10)]GnRH yielded analogues that blocked ovulation at 250 mu g/rat. Analogue 14 (K-i = 2.3 nM), with a [DAsp(3), Lys(8)] bridge, was fully active at 50 mu g/rat. Loss of potency (> 20-fold) was observed with the substitution of [DAsp(3)] in 14 by [DGlu(3)] in 15 (K-i = 23 nM), Dicyclic analogues possessing the (4-10) cycle and selected (1-6), (2-6), and (2-8) cycles led to analogues that were inactive at doses of 500 mu g/rat or larger. Two analogues with (1-8/4-10) cycles (16, K-i = 1.1 nM) or (3-8/4-10) cycles (22, K-i = 17 nM) showed full antiovulatory potency at 250 mu g/rat. None of these substitutions yielded analogues potent enough (>80% inhibition of ovulation at 5 mu g/rat or less and K-i < 0.5 nM) to be candidates for structural analysis by NMR. On the other hand, four dicyclic (1,1'-5/4-10) analogues met this criterion: dicyclo(1,1'-5/4-10)[Ac-Asp(1)(Gly),DCpa(2),DTrp(3),Asp(4),Dbu(5), DNal(6),Dpr(10)]GnRH (32, K-i = 0.22 nM), dicyclo(1,1'-5/4-10)[Ac-Asp(1)(Gly),DCpa(2),DTrp(3),Asp(4),Dbu(5), DNal(6),Dpr(10)]GnRH (34, K-i = 0.38 nM), dicyclo(1,1'-5/4 - 10)[Ac-Asp(1)(beta Ala),DCpa(2), DTrp(3),Asp(4),Dbu(5),DNal(6),Dpr(10)]GnRH (40, K-i = 0.15 nM), and dicyclo(1,1'-5/4-10)[Ac-Glu(1)(Gly), DCpa(2),DTrp(3),Asp(4),Dbu(5),DNal(6),Dpr(10)]GnRH (41, K-i = 0.24 nM). Since they differed slightly in terms of the (1,1'-5) bridge length (21 and 22 atoms) and bridgehead configuration, we may hypothesize that they assume similar bioactive conformations that satisfy a very discriminating receptor, since many other closely related analogues were significantly less potent.
• Ring Size in Octreotide Amide Modulates Differently Agonist versus Antagonist Binding Affinity and Selectivity
  作者：Christy Rani R. Grace、Judit Erchegyi、Manoj Samant、Renzo Cescato、Veronique Piccand、Roland Riek、Jean Claude Reubi、Jean E. Rivier

  DOI：10.1021/jm701445q

  日期：2008.5.1

  H-DPhe(2)-c[Cys(3) -Phe(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Thr(15) -NH(2) (1) (a somatostatin agonist, SRIF numbering) and H-Cpa(2) -c[DCys(3) -Tyr(7) -DTrp(8)-Lys(9)-Thr(10)-Cys(14)] -Nal(15)-NH(2) (4) (a somatostatin antagonist) are based on the structure of octreotide that binds to three somatostatin receptor subtypes (SSt(2/3/5)) with significant binding affinity. Analogues of 1 and 4 were synthesized with norcysteine (Ncy), homocysteine (Hcy), or D-homocysteine (DHcy) at positions 3 and/or 14. Introducing Ncy at positions 3 and 14 constrained the backbone flexibility, resulting in loss of binding affinity at all sst(s) The introduction of Hey at positions 3 and 14 improved selectivity for sst(2) as a result of significant loss of binding affinity at the other ssts. Substitution by DHcy at position 3 in the antagonist scaffold (5), on the other hand, resulted in a significant loss of binding affinity at sst(2) and sst(3) as compared to the different affinities of the parent compound (4). The 3D NMR structures of the analogues in dimethylsulfoxide are consistent with the observed binding affinities.