N,N'-di-t-butoxycarbonyl-3,5-dimetylpyrazolyl-1-carboxamidine | 153114-31-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N'-di-t-butoxycarbonyl-3,5-dimetylpyrazolyl-1-carboxamidine
• 英文别名: N,N'-bis-(t-Butyloxycarbonyl)-3,5-dimethyl-1H-pyrazole-1-carboxamidine；tert-butyl (NZ)-N-[(3,5-dimethylpyrazol-1-yl)-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate
• CAS: 153114-31-9
• 化学式: C₁₆H₂₆N₄O₄
• 分子量: 338.407
• InChiKey: ZWLXESMNQHVOQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N,N'-di-t-butoxycarbonyl-3,5-dimetylpyrazolyl-1-carboxamidine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 38.0h， 生成 N,N'-bis(tert-butoxycarbonyl)-6-guanidinylcaproic acid
  参考文献：
  名称：

  Synthesis and evaluation of RGD peptidomimetics aimed at surface bioderivatization of polymer substrates

  摘要：

  Several RGD peptidomimetics have been prepared, in a convergent way, from the common ortho-amino-tyrosine template (O-substituted with an anchorage-arm or a methyl group, and alpha N-substituted with a fluorine tag for XPS analysis), and various omega-aminoacid derivatives. The most flexible compounds have shown a biological activity similar to that of the peptide reference (RGDS) in the platelet aggregation test. The compound 16a could be fitted (by modelisation) with DMP 728 and c(RGDfV), two cyclic peptides that are good ligands of integrins. The compound 16b has been covalently fixed on the surface of a poly(ethylene terephthalate) membrane used as support for mammalian cell cultivation. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00083-2
• 作为产物：
  描述：

  3,5-二甲基吡唑 、 N,N′-二-Boc-硫脲 在 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以87%的产率得到N,N'-di-t-butoxycarbonyl-3,5-dimetylpyrazolyl-1-carboxamidine
  参考文献：
  名称：

  制备胍的改进方法

  摘要：

  在氯化汞的存在下使用N，N'-二-（叔丁氧基羰基）硫脲1提供了一种非常有效的方法，用于双-Boc保护的氨基化合物的空间或电子高度失活的胍形成。

  DOI：

  10.1016/s0040-4039(00)61537-x

文献信息

• Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
  作者：Chu-Biao Xue、John Wityak、Thais M. Sielecki、Donald J. Pinto、Douglas G. Batt、Gary A. Cain、Michael Sworin、Arlene L. Rockwell、John J. Roderick、Shuaige Wang、Michael J. Orwat、William E. Frietze、Lori L. Bostrom、Jie Liu、C. Anne Higley、F. Wayne Rankin、A. Ewa Tobin、George Emmett、George K. Lalka、Jean Y. Sze、Susan V. Di Meo、Shaker A. Mousa、Martin J. Thoolen、Adrienne L. Racanelli、Elizabeth A. Hausner、Thomas M. Reilly、William F. DeGrado、Ruth R. Wexler、Richard E. Olson

  DOI：10.1021/jm960799i

  日期：1997.6.1

  Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of

  使用异恶唑啉XR299（1a）作为设计高效，长效GPIIb / IIIa拮抗剂的起点，评估了将亲脂性取代基置于羧酸酯部分的α和β处的效果。在所研究的化合物中，发现氨基甲酸正丁酯24u在狗中表现出优异的效力和离体抗血小板作用的持续时间。用可替代的碱性基团取代苯并胺丁-4-基部分，消除异恶唑啉立体中心，并改变异恶唑啉环的方向，导致效力和/或作用时间降低。
• Solid phase synthesis of a diketopiperazine catalyst containing the unnatural amino acid (S)-norarginine
  作者：Jennifer Kowalski、Mark A. Lipton

  DOI：10.1016/0040-4039(96)01239-7

  日期：1996.8

  A cyclic dipeptide containing the unnatural amino acid (S)-norarginine, recently shown to display useful catalytic activity, has been synthesized in good yield and high chemical purity using a solid phase protocol. All reactions in the sequence, including a Hofmann rearrangement and cyclization to diketopiperazine, were performed on the Merrifield polystyrene resin and proceed in high yield. In addition

  使用固相方案以高收率和高化学纯度合成了包含非天然氨基酸（S）-去甲精氨酸的环状二肽，最近显示出其显示出有用的催化活性。该序列中的所有反应，包括霍夫曼重排和环化成二酮哌嗪，均在Merrifield聚苯乙烯树脂上进行，并以高收率进行。除了提高产量外，这种新的合成方法还易于获得衍生物，并有可能采用组合策略来寻找新型的催化环二肽。
• Control of the Molecular Packing in Guanidinium Monolayers through Binding with Aqueous Polycarboxylates
  作者：Ayumi Kamino、Hiroshi Koyano、Katsuhiko Ariga、Toyoki Kunitake

  DOI：10.1246/bcsj.69.3619

  日期：1996.12

  By using newly developed guanylating agents, octadecyl- and dioctadecylguanidinium amphiphiles were synthesized. The interaction between each guanidinium monolayer and polycarboxylates in the subphase was investigated on the basis of the π–A isotherm, FT-IR spectroscopy, and XPS measurements. When linear dicarboxylates were used, the molecular areas of the monolayer increased, as the length of the methylene chain between the carboxylate groups increased. The expansion of the molecular area was greater for the octadecylguanidinium monolayers than for the dioctadecylguanidinium monolayers. The molecular packing was affected by the shape of polycarboxylate molecules in the case of phthalate, cis-1,2-cyclohexanedicarboxylate, and 1,1-cyclohexanediacetate. It is clear that, the molecular packing in the complexed monolayers is governed by the distance and relative orientation of the two carboxylate groups in a polycarboxylate. With all of the dicarboxylates, excluding oxalate, FT-IR and XPS measurements of the LB films indicated the formation of 1 : 1 guanidinium/carboxylate pairs with hydrogen bonding interactions. Oxalate produced an asymmetric complex where one guanidinium was bound to oxalate through hydrogen bonding, and the other guanidinium existed as a non-hydrogen bonded counter ion. These results are useful for the development of two-dimensional molecular patterns.

  利用新开发的鸟苷酸化剂合成了十八烷基和双十八烷基鸟苷酸双亲化合物。根据π-A 等温线、傅立叶变换红外光谱和 XPS 测量，研究了每种胍单层与亚相中的聚羧酸盐之间的相互作用。当使用线性二羧酸盐时，随着羧酸盐基团之间亚甲基链长度的增加，单层的分子面积也随之增加。十八烷基胍单层分子面积的扩大程度大于双十八烷基胍单层。邻苯二甲酸酯、顺式-1,2-环己烷二甲酸酯和 1,1-环己烷二乙酸酯的分子堆积受聚羧酸酯分子形状的影响。显然，络合单层中的分子堆积受聚羧酸盐中两个羧酸基团的距离和相对方向的影响。对于除草酸盐以外的所有二羧酸盐，枸杞薄膜的傅立叶变换红外光谱和 XPS 测量结果表明，胍/羧酸盐对形成了 1:1 的氢键相互作用。草酸盐产生了一种不对称复合物，其中一个胍通过氢键与草酸盐结合，另一个胍作为非氢键反离子存在。这些结果有助于开发二维分子模式。
• Aminothiazolidine and aminotetrahydrothiazepine derivatives as BACE 1 inhibitors
  申请人：Shionogi & Co., Ltd.

  公开号：EP2612854A1

  公开（公告）日：2013-07-10

  A composition having BACE 1 inhibitory activity containing a compound represented by the general formula (I): wherein ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; E is lower alkylene; X is S, O, or NR1; R1 is a hydrogen atom or lower alkyl; R2a, R2b, R3a, R3b, R4a and R4b is each independently a hydrogen atom, halogen, or hydroxy etc.; n and m are each independently an integer of 0 to 3; n+m is an integer of 0 to 3; R5 is a hydrogen atom or substituted lower alkyl; its pharmaceutically acceptable salt, or a solvate thereof.

  一种具有 BACE 1 抑制活性的组合物，含有通式 (I) 所代表的化合物： 其中环 A 是任选取代的碳环基团或任选取代的杂环基团； E 是低级亚烷基 X 是 S、O 或 NR1； R1 是氢原子或低级烷基； R2a、R2b、R3a、R3b、R4a 和 R4b 各自独立地为氢原子、卤素或羟基等； n 和 m 各自独立地为 0 至 3 的整数； n+m 是 0 至 3 的整数； R5 是氢原子或取代的低级烷基； 其药学上可接受的盐或其溶液。
• α_vβ₃ Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers
  作者：Vincent Rerat、Georges Dive、Alex A. Cordi、Gordon C. Tucker、Reine Bareille、Joëlle Amédée、Laurence Bordenave、Jacqueline Marchand-Brynaert

  DOI：10.1021/jm901133z

  日期：2009.11.26

  RGD peptides are used in biomaterials science for surface modifications with a view to elicit selective cellular responses. Our objective is to replace peptides by small peptidomimetics acting similarly. We designed novel molecules targeting alpha(v)beta(3) integrin and featuring spacer-arms (for surface grafting), which do not disturb the biological activity, from (L) N-(3-(trifluoromethyl)benzenesulfonyl) tyrosine used as scaffold. Various Arg-mimics were fixed on the phenol function, and the ortho position was used for the Coupling of OEG spacers. All peptidomimetics were active in the nM range in a binding test toward human alpha(v)beta(3) integrin (IC50 = 0.1 to 1.7 nM) and selective versus platelet integrin alpha(IIb)beta(3) Selected compounds revealed excellent ability to inhibit bone cells adhesion on vitronectin. Modeling and docking studies were performed for comparing the most active RGD peptidomimetic to cilengitide, i.e., cyclo-[RGDfN(Me)V]-. Lastly, the adhesion of endothelial cells on a cultivation support grafted with RGD peptidomimetics was significantly improved.