2-amino-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine hydrobromide

• 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-amino-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine hydrobromide
• 英文别名: 2-amino-5-(4-chlorophenyl)-1,3,4-thiadiazine hydrobromide；2-amino-5-(4-chlorohenyl)-6H-1,3,4-thiadiazine hydrobromide；5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-2-aminium bromide；5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-3-ium-2-amine;bromide
• 化学式: BrH*C₉H₈ClN₃S
• 分子量: 306.614
• InChiKey: AMABWUMMPIGOJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine hydrobromide 在 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 反应 0.25h， 生成 5-(4-chlorophenyl)-3-heptyl-N-nitroso-3,6-dihydro-2H-1,3,4-thiadiazin-2-imine
  参考文献：
  名称：

  Rehse; Bruemmer; Unsoeld, Pharmazie, 1998, vol. 53, # 12, p. 820 - 824

  摘要：

  DOI：
• 作为产物：
  描述：

  在 48percent aq. HBr 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 2-amino-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine hydrobromide
  参考文献：
  名称：

  Structure-Based Design and Synthesis of Potent Matrix Metalloproteinase Inhibitors Derived from a 6H-1,3,4-Thiadiazine Scaffold

  摘要：

  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.

  DOI：

  10.1021/jm010887p

文献信息

• Thiadiazines and their use as inhibitors of metalloproteinases
  申请人：Tschesche, Harald

  公开号：EP1191024A1

  公开（公告）日：2002-03-27

  The present invention provides novel thiadiazines represented by formula (I) which are useful as inhibitors of metalloproteinases. Also disclosed are pharmaceutical compositions and methods of treating disorders associated with increased activity of metalloproteinases using these compounds or the pharmaceutical compositions containing them.

  本发明提供了一种新型的噻二唑类化合物，其化学式表示为（I），这些化合物可用作金属蛋白酶的抑制剂。还公开了使用这些化合物或含有它们的药物组合物治疗与金属蛋白酶活性增加相关的疾病的方法和药物组合物。
• Synthesis of Imidazo[2,1-<i>b</i>][2<i>H</i>-1,3,4]thiadiazines and 1,2,4-Triazolo[3,4-<i>b</i>][2<i>H</i>-1,3,4]thiadiazines
  作者：Stefanie Knak、Wolf-Diethard Pfeiffer、Horst Dollinger、Ashot S. Saghyan、Peter Langer

  DOI：10.1002/jhet.2074

  日期：2015.3

  Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.
• 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.
• Rehse; Bruemmer; Unsoeld, Pharmazie, 1998, vol. 53, # 12, p. 820 - 824
  作者：Rehse、Bruemmer、Unsoeld

  DOI：——

  日期：——