2-amino-5-phenyl-6H-1,3,4-thiadiazine hydrochloride | 74495-44-6

• 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-phenyl-6H-1,3,4-thiadiazine hydrochloride
• 英文别名: 5-phenyl-6H-1,3,4-thiadiazin-3-ium-2-amine;chloride
• CAS: 74495-44-6
• 化学式: C₉H₉N₃S*ClH
• mdl: MFCD06801343
• 分子量: 227.718
• InChiKey: FWCMBEVJMSPOID-UHFFFAOYSA-N

物化性质

• 熔点：
  210 °C (decomp)

计算性质

• 辛醇/水分配系数(LogP)：
  1.39
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.111
• 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-phenyl-6H-1,3,4-thiadiazine hydrochloride 在 sodium acetate 、 sodium nitrite 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.25h， 生成 3-allyl-N-nitroso-5-phenyl-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：

  氨基硫脲单盐酸盐 、 alpha-氯乙酰苯 以 甲醇 为溶剂， 反应 0.25h， 以43%的产率得到2-amino-5-phenyl-6H-1,3,4-thiadiazine hydrochloride
  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

• The rearrangement of 2-amino-1,3,4-thiadiazines to 3-amino-2-thiazolimines. Part 1. The rates of rearrangement of a series of 5-alkyl- and 5-aryl-2-amino-1,3,4-thiadiazines at 30 and 50 °C
  作者：Reginald E. Busby、Terence W. Dominey

  DOI：10.1039/p29800000890

  日期：——

  The rates of rearrangement of the series 5-methyl-, 5-ethyl-, 5-isopropyl-, and 5-t-butyl-2-amino-1,3,4-thiadiazines in strong acid have been followed by observing the u.v. absorptions of the protonated thiadiazine substrates or the product thiazolimines. The rates of rearrangement were found to be first order with respect to the thiadiazine concentration and the rates decreased along the series in

  在强酸中观察了5-甲基-，5-乙基-，5-异丙基-和5-叔丁基-2-氨基-1,3,4-噻二嗪系列的重排速率，并观察了uv。质子化的噻二嗪底物或产物噻唑啉的吸收。发现重排的速率相对于噻二嗪浓度是一阶的，并且该速率以S N 2反应的特征沿着系列下降。2-氨基-1,3,4-噻二嗪与苯基，对硝基苯基和p的重排速率在5位的-羟基苯基基团都非常慢，而2-氨基-5-苄基-1,3,4-噻二嗪的重排比这些芳基噻二嗪快得多，但比5-甲基和5-乙基化合物慢得多。在4.47–8.12 M -HCl范围内的各种酸强度下，遵循2-氨基-5-甲基-1,3,4-噻二嗪的重排速率。反应最终达到平衡，并且测得的常数k 1等于正向和反向反应的速度常数（k r + k –r）之和。既ķ ř和ķ -r被认为是类似地依赖于酸度和水分活度。使用HLong和Paul用取代的苯胺得到0个值，发现对数10 k 1对– H 0的图是线性的，斜率等于0
• 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：——