2-(S)-<<(tert-butyloxy)carbonyl>amino>-6-(3-o-tolylureido)hexanoic acid | 131451-45-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(S)-<<(tert-butyloxy)carbonyl>amino>-6-(3-o-tolylureido)hexanoic acid
• 英文别名: N-α-Boc-L-lysine<(N^ε-o-tolylamino)carbonyl>；Boc-Lys(CONH-Ph-o-Me)-OH；BOC-Lys(Tac)-OH；(2S)-6-[(2-methylphenyl)carbamoylamino]-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 131451-45-1
• 化学式: C₁₉H₂₉N₃O₅
• 分子量: 379.456
• InChiKey: MZOODEATOYXMNR-HNNXBMFYSA-N

物化性质

• 沸点：
  556.6±50.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(S)-<<(tert-butyloxy)carbonyl>amino>-6-(3-o-tolylureido)hexanoic acid 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 、 lithium aluminium tetrahydride 、 sodium azide 、 ethylcarbodiimide hydrochloride 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 氯甲酸异丁酯 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 103.75h， 生成 N-<2-<<2-(S)-<<(adamantan-2-yloxy)carbonyl>amino>-3-(1H-indol-3-yl)-2-(R)-methylpropionyl>amino>-6-(3-o-tolylureido)hexyl>succinamic acid
  参考文献：
  名称：

  Modification of Receptor Selectivity and Functional Activity in Cholecystokinin Peptoid Ligands

  摘要：

  Hybrid analogs of the cholecystokinin A (CCK-A) receptor selective tetrapeptide agonist Boc-Trp-Lys(Tac)-Asp-MePhe-NH2 (1, A-71623) and the CCK-B receptor selective antagonists PD-135118 (2) and CI-988 (3) were prepared. Incorporation of the Lys(Tac) side chain into 2 produced a moderately potent antagonist of CCK-8 in the isolated guinea pig gallbladder (GPGB). Incorporation of the Lys(Tac) side chain into 3 produced the novel agonist analog 7 (EC(50) = 28 nM in the GPGB) with excellent affinity for both human CCK-A (IC50 = 12 nM) and CCK-B (IC50 = 17 nM) receptors. Analog 7 was a full agonist (EC(50) = 3.5 nM) for calcium mobilization on CHO-K1 cells expressing hCCK-A receptors but a partial agonist on CHO-K1 cells expressing hCCK-B receptors, eliciting a weak agonist reponse (EC(50) = 2800 nM) and antagonizing CCK-8-induced calcium mobilization (K-B = 20 nM). Despite this unusual in vitro profile, analog 7 was a potent anorectic agent in rats (ED(50) = 30 nmol/kg) following intraperitoneal administration.

  DOI：

  10.1021/jm00017a022
• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 、 邻甲苯异氰酸酯 在 sodium hydroxide 作用下， 反应 3.0h， 以94%的产率得到2-(S)-<<(tert-butyloxy)carbonyl>amino>-6-(3-o-tolylureido)hexanoic acid
  参考文献：
  名称：

  来自CCK-A受体选择性四肽激动剂Boc-Trp-Lys（Tac）-Asp-MePhe-NH2（A-71623）的CCK-A受体选择性拮抗剂。

  摘要：

  制备了CCK-A受体选择性激动剂Boc-Trp-Lys（Tac）-Asp-MePhe-NH2（A-71623）的类似物，其中赖氨酸残基被L-4-氨基苯丙氨酸和D-或L-3取代-氨基苯丙氨酸。这些新的类似物是分离的豚鼠胆囊中CCK-8的中度有效拮抗剂，具有出色的CCK-A受体选择性，这在稳定转染了人CCK-A和CCK-B受体的CHO K1细胞膜制剂中得到了评估。

  DOI：

  10.1021/jm00001a027

文献信息

• Novel Asp32-Replacement Tetrapeptide Analogs as Potent and Selective CCK-A Agonists
  作者：Richard L. Elliott、Hana Kopecka、Michael D. Tufano、Youe-Kong Shue、Andre J. Gauri、Chun-Wel Lin、Bruce R. Bianchi、Thomas R. Miller、David G. Witte

  DOI：10.1021/jm00037a005

  日期：1994.5

  penultimate position, demonstrated surprisingly high CCK-A receptor affinity and selectivity. The effect of N-methylation pattern on CCK-A receptor affinity showed consistent trends for analogues in which n = 1, 2, or 3, with the di-N-methylated analogues having the highest affinity in each case. However, none of these analogues had full agonist activity, as measured by percent maximal PI hydrolysis

  一系列通式为Boc-Trp-Lys（Tac）-N（R）-（CH2）nCON（R'）Phe-NH2的新颖CCK四肽类似物（Tac =邻甲苯基氨基羰基），其中R，R'= H或Me且n = 1-5，已经合成和测试。这些类似物在倒数第二个位置缺少酸性残基，显示出令人惊讶的高CCK-A受体亲和力和选择性。N-甲基化模式对CCK-A受体亲和力的影响显示出对n = 1、2或3的类似物的一致趋势，其中二-N-甲基化类似物在每种情况下均具有最高亲和力。然而，通过最大PI水解百分数测量，这些类似物均不具有完全的激动剂活性。两种受构象限制的类似物也显示出高CCK-A受体亲和力和选择性，以及几乎最大的激动剂活性。此外，
• Tetrapeptide CCK agonists: structure-activity studies on modifications at the N-terminus
  作者：Richard L. Elliott、Hana Kopecka、Michael J. Bennett、Youe Kong Shue、Richard Craig、Chun Wel Lin、Bruce R. Bianchi、Thomas R. Miller、David G. Witte

  DOI：10.1021/jm00028a015

  日期：1994.1

  We had reported earlier(1) on a novel series of potent and selective tetrapeptide cholecystokinin-A (CCK-A) agonists of the general structure Boc-Trp-Lys[epsilon-Y]-Asp-N(R)PheNH(2) [Y = amides, ureas; R = H, Me] that were potent anorectic agents in rats. In an effort to optimize the potency, selectivity, stability, and efficacy of our lead candidate A-71623 [R = Me, Y = o-tolylaminocarbonyl; Tac] toward-development of a clinical candidate; we have explored a series of analogues in which the N-terminal Boc functionality was systematically replaced with various amides, ureas, carbamates, and sulfonamides of differing size, hydrophobicity; and stereoelectronic properties. In;general, these analogues maintained good potency and selectivity for the CCK-A receptor (guinea pig pancreas), as well as potent anorectic activity in rats. Those analogues exhibiting equal or superior activity compared to A-71623 but differing physicochemical properties may represent superior drug candidates.
• Holladay; Kopecka; Miller, Journal of Medicinal Chemistry, 1994, vol. 37, # 5, p. 630 - 635
  作者：Holladay、Kopecka、Miller、Bednarz、Nikkel、Bianchi、Witte、Shiosaki、Chun Wel Lin、Asin、Nadzan

  DOI：——

  日期：——
• The design and synthesis of the high efficacy, non-peptide CCK 1 receptor agonist PD 170292
  作者：N. Bernad、B.G.M. Burgaud、D.C. Horwell、R.A. Lewthwaite、J. Martinez、M.C. Pritchard

  DOI：10.1016/s0960-894x(00)00198-0

  日期：2000.6

  The design, synthesis and biological actions of a novel, non-peptide CCK1 receptor agonist (PD 170292) which exhibits a similar pharmacological profile to the CCK analogue JMV180 is reported. PD 170292 was designed based on a consideration of the structures of a peptide based CCK1 receptor selective agonist and a peptoid CCK2 receptor selective antagonist. (C) 2000 Elsevier Science Ltd. All rights reserved.