(2R)-3-methyl-2-[(phenylsulfonyl)amino]butyric acid | 371196-69-9

• 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
• 英文名称: (2R)-3-methyl-2-[(phenylsulfonyl)amino]butyric acid
• 英文别名: (2R)-2-(benzenesulfonamido)-3-methylbutanoic acid
• CAS: 371196-69-9
• 化学式: C₁₁H₁₅NO₄S
• 分子量: 257.31
• InChiKey: AGDVYAPPQUVBHB-SNVBAGLBSA-N

物化性质

• 熔点：
  148-149 °C
• 沸点：
  431.5±47.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  91.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-3-methyl-2-[(phenylsulfonyl)amino]butyric acid 在 N-甲基吗啉 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  控制异羟肟酸的血浆稳定性：MedChem工具箱

  摘要：

  异羟肟酸是杰出的锌螯合基团，可用于设计各种治疗领域中的有效和选择性金属酶抑制剂。一些异羟肟酸显示出较高的血浆清除率，导致体内活性差，尽管它们在体外可能是非常有效的化合物。我们设计了一个由57名成员组成的异羟肟酸文库，以探索这些系列中结构与血浆的稳定性关系，并确定哪些酶和哪些药效团对血浆稳定性至关重要。芳基酯酶和羧酸酯酶被确定为异羟肟酸的主要代谢酶。最后，我们建议引入或删除结构特征以提高稳定性。因此，这项工作提供了第一个药物化学工具箱（实验程序和结构指导），用于评估和控制异羟肟酸的血浆稳定性，并充分发挥其作为体内药理探针和治疗剂的潜力。这项研究与临床前开发特别相关，因为它允许获得在人和啮齿动物模型中同样稳定的化合物。

  DOI：

  10.1021/acs.jmedchem.7b01444
• 作为产物：
  描述：

  tosyl-vaniline 在 C₄₆H₄₆ClP₂RuS₂⁽¹⁺⁾*Cl^(1-) 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、721.87 kPa 条件下， 反应 17.0h， 以99%的产率得到(2R)-3-methyl-2-[(phenylsulfonyl)amino]butyric acid
  参考文献：
  名称：

  [EN] PROCESS FOR MAKING N-SULFONATED-AMINO ACID DERIVATIVES
  [FR] PROCEDE DE FABRICATION DE DERIVES D'ACIDES AMINES N-SULFONES

  摘要：

  公开号：

  WO2005118529A3

文献信息

• Enantioselective [3 + 2] Cycloaddition of Allenes to Acrylates Catalyzed by Dipeptide-Derived Phosphines: Facile Creation of Functionalized Cyclopentenes Containing Quaternary Stereogenic Centers
  作者：Xiaoyu Han、Youqing Wang、Fangrui Zhong、Yixin Lu

  DOI：10.1021/ja1106282

  日期：2011.2.16

  A new family of dipeptide-based chiral phosphines was designed and prepared. D-Thr-L-tert-Leu-derived catalyst 4c promoted [3 + 2] cycloaddition of allenoates to α-substituted acrylates in a regiospecific and stereoselective manner, furnishing functionalized cyclopentenes with quaternary stereogenic centers in high yields and with excellent enantioselectivities.

  设计并制备了一个新的基于二肽的手性膦家族。D-Thr-L-tert-Leu 衍生的催化剂 4c 以区域专一性和立体选择性的方式促进了烯丙酸酯的 [3 + 2] 环加成反应到 α-取代的丙烯酸酯，以高产率和优异的对映选择性提供具有四元立体中心的官能化环戊烯。
• [EN] PROCESS FOR THE SYNTHESIS OF 2-[(2S)-1-AZABICYCLO[2.2.2]OCT-2-YL]-6- (3-METHYL-1 H-PYRAZOL-4-YL)THIENO[3,2-D]PYRIMIDIN-4(3H)-ONE<br/>[FR] PROCÉDÉS DE SYNTHÈSE DE 2-[(2S)-1-AZABICYCLO[2.2.2]OCT-2-YL]-6- (3-MÉTHYL-1 H-PYRAZOL-4-YL)THIÉNO[3,2-D]PYRIMIDIN-4(3H)-ONE
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2019194319A1

  公开（公告）日：2019-10-10

  The present invention provides processes and synthetic intermediates for the synthesis of 2-[(2S)-l- azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-lH-pyrazol-4- yl)thieno[3,2-d]pyrimidin-4 3H) -one or a salt, hydrate, or tautomer thereof, or any combination thereof, which are Cdc7 kinase inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with Cdc7 activity.

  本发明提供了合成2-[(2S)-1-氮杂双环[2.2.2]辛-2-基]-6-(3-甲基-1H-吡唑-4-基)噻唑并[3,2-d]嘧啶-4(3H)-酮或其盐、水合物或互变异构体的过程和合成中间体，这些化合物是Cdc7激酶抑制剂，可用于治疗细胞增殖紊乱，特别是癌症，以及与Cdc7活性相关的其他疾病。
• Process for the synthesis of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US11524957B2

  公开（公告）日：2022-12-13

  The present invention provides processes and synthetic intermediates for the synthesis of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4 3H)-one or a salt, hydrate, or tautomer thereof, or any combination thereof, which are Cdc7 kinase inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with Cdc7 activity.

  本发明提供了合成 2-[(2S)-1-氮杂双环[2.2.2]辛-2-基]-6-(3-甲基-1H-吡唑-4-基)噻吩并[3,2-d]嘧啶-4 3H)-酮或其盐、水合物或同系物，或其任意组合，它们是Cdc7激酶抑制剂，可用于治疗细胞增殖紊乱，特别是癌症，以及与Cdc7活性相关的其他紊乱。
• Structure-Based Design and Synthesis of Potent Matrix Metalloproteinase Inhibitors Derived from a 6<i>H</i>-1,3,4-Thiadiazine Scaffold
  作者：Jörg Schröder、Andreas Henke、Herbert Wenzel、Hans Brandstetter、Hans G. Stammler、Anja Stammler、Wolf D. Pfeiffer、Harald Tschesche

  DOI：10.1021/jm010887p

  日期：2001.9.1

  We describe a new generation of heterocyclic nonpeptide matrix metalloproteinase (MMP) inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. A screening effort was utilized to identify some chiral 6-methyl-1,3,4-thiadiazines that are weak inhibitors of the catalytic domain of human neutrophil collagenase (cdMMP-8). Further optimization of the lead compounds revealed general design principles that involve the placement of a phenyl or thienyl group at position 5 of the thiadiazine ring, to improve unprimed side affinity; the incorporation of an amino group at position 2 of the thiadiazine ring as the chelating agent for the catalytic zinc; the placement of a N-sulfonamide-substituted amino acid residue at the amino group, to improve primed side affinity; and the attachment of diverse functional groups at position 4 or 5 of the phenyl or thienyl group at the unprimed side, to improve selectivity. The new compounds were assayed against eight different matrix metalloproteinases, MMP-1, cdMMP-2, cdMMP-8, MMP-9, cdMMP-12, cdMMP-13, cdMMP-14, and the ectodomain of MMP-14, respectively. A unique combination of the above-described modifications produced the selective inhibitor (2R)-N-[5-(4-bromophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide with high affinity for MMP-9 (K-i = 40 nM). X-ray crystallographic data obtained for cdMMP-8 cocrystallized with N-allyl-5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-2-amine hydrobromide gave detailed design information on binding interactions for thiadiazine-based MMP inhibitors.
• PROCESS FOR THE SYNTHESIS OF 2-[(2S)-1-AZABICYCLO[2.2.2]OCT-2-YL]-6-(3-METHYL-1H-PYRAZOL-4-YL)THIENO[3,2-d]PYRIMIDIN-4(3H)-ONE
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20210101897A1

  公开（公告）日：2021-04-08

  The present invention provides processes and synthetic intermediates for the synthesis of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4 (3H)-one or a salt, hydrate, or tautomer thereof, or any combination thereof, which are Cdc7 kinase inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with Cdc7 activity.