(S)-2,3,3-Trimethylbutylamin | 74669-71-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-2,3,3-Trimethylbutylamin
• 英文别名: (2S)-2,3,3-trimethylbutan-1-amine
• CAS: 74669-71-9
• 化学式: C₇H₁₇N
• 分子量: 115.219
• InChiKey: CGXTZRLPKKSQOC-ZCFIWIBFSA-N

物化性质

• 沸点：
  125.5±8.0 °C(Predicted)
• 密度：
  0.777±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-2,3,3-Trimethylbutylamin 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands

  摘要：

  A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S-2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P-2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

  DOI：

  10.1021/acs.jmedchem.6b00998
• 作为产物：
  描述：

  3,3-二甲基丁酰氯 在 lithium aluminium tetrahydride 、 正丁基锂 、 双氧水 、 二异丙胺 、 三苯基膦 、 lithium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 水 为溶剂， 反应 75.0h， 生成 (S)-2,3,3-Trimethylbutylamin
  参考文献：
  名称：

  Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands

  摘要：

  A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S-2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P-2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

  DOI：

  10.1021/acs.jmedchem.6b00998

文献信息

• Enantioselective CuH-Catalyzed Anti-Markovnikov Hydroamination of 1,1-Disubstituted Alkenes
  作者：Shaolin Zhu、Stephen L. Buchwald

  DOI：10.1021/ja509786v

  日期：2014.11.12

  Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could

  β-手性胺的对映选择性合成是通过铜催化的 1,1-二取代烯烃与羟胺酯在氢硅烷存在下的加氢胺化反应实现的。这种温和的方法以优异的收率和高对映选择性提供了一系列结构多样的 β-手性胺，包括 β-氘化胺。此外，可以采用低至 0.4 mol% 的催化剂负载量以不降低产率和选择性提供产品，证明了该方法用于大规模合成的实用性。
• Kinase antagonists
  申请人：Knight A. Zachary

  公开号：US20070293516A1

  公开（公告）日：2007-12-20

  The present invention provides novel compounds that are antagonists of PI3 kinase, PI3 kinase and tryosine kinase, PI3Kinase and mTOR, or PI3Kinase, mTOR and tryosine kinase.

  本发明提供了一种新型化合物，它们是 PI3 激酶、PI3 激酶和酪氨酸激酶、PI3 激酶和 mTOR，或者 PI3 激酶、mTOR 和酪氨酸激酶的拮抗剂。
• KINASE INHIBITORS AND METHODS OF USE
  申请人：Liu Yi

  公开号：US20110077268A1

  公开（公告）日：2011-03-31

  The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating lipid kinases such PB kinases, tryosine kinases and protein kinases such as mTOR. Also provided in the present invention are methods of using these compositions to modulate these kinases especially for therapeutic applications.

  本发明提供了能够调节脂质激酶如PB激酶、酪氨酸激酶和蛋白激酶如mTOR的化学实体或化合物及其制药组合物。本发明还提供了使用这些组合物来调节这些激酶的方法，特别是用于治疗应用的方法。
• NOVEL NICOTINAMIDE DERIVATIVE OR SALT THEREOF
  申请人：FUJIWARA Hideyasu

  公开号：US20130116430A1

  公开（公告）日：2013-05-09

  An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R 1 represents a halogen atom; R 2 represents a C 1-12 alkyl group, a C 2-12 alkenyl group, a C 2-12 alkynyl group, a C 3-8 cycloalkyl group, an aryl group, an ar-C 1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R 3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R 4 and R 5 each independently represent a hydrogen atom; and R 2 and R 4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

  本发明的目的是提供一种具有优异的Syk抑制活性的化合物和制药组合物。本发明提供了一种由以下式(I)表示的烟酰胺衍生物（其中R1表示卤素原子；R2表示C1-12烷基、C2-12烯基、C2-12炔基、C3-8环烷基、芳基、芳基-C1-6烷基或杂环基，每种均可选地具有至少一个取代基；R3表示芳基或杂环基，每种均可选地具有至少一个取代基；R4和R5各自独立地表示氢原子；且R2和R4可以与它们结合的氮原子一起形成具有至少一个取代基的环状氨基团）或其盐，并且用于治疗Syk相关疾病的制药组合物包括该烟酰胺衍生物或其盐。
• DERIVATIVES OF SOBETIROME
  申请人：Scanlan Thomas S.

  公开号：US20160244418A1

  公开（公告）日：2016-08-25

  Ester derivatives of sobetirome with enhanced CNS distribution are disclosed.

  本发明公开了具有增强中枢神经系统分布的Sobetirome的Ester衍生物。