(2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid

• ChemBase编号: 72570
• 分子式: C21H22N4O6S
• 平均质量: 458.48758
• 单一同位素质量: 458.12600544
• SMILES: C(=O)([C@H](CCC(=O)O)NC(=O)c1ccc(s1)N(Cc1cc2c(=O)[nH]c(nc2cc1)C)C)O
• Canonical SMILES: OC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(s1)N(Cc1ccc2c(c1)c(=O)[nH]c(n2)C)C
• InChI: InChI=1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13(14)19(28)23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21(30)31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1
• InChIKey: IVTVGDXNLFLDRM-HNNXBMFYSA-N

名称和登记号

名称

• IUPAC标准名: (2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid
• IUPAC传统名: (2S)-2-[(5-{methyl[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid; (2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid
• 别名: N-[[5-[[(1,4-Dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]methylamino]-2-thienyl]carbonyl]-L-glutamic Acid; ICI-D-1694; ZD-1694; Raltitrexed; Tomudex; Raltitrexed(Tomudex); Raltitrexed

登记号

• CAS号: 112887-68-0
• PubChem SID: 162037495
• PubChem CID: 104758

理论计算性质

• Acid pKa: 3.9605484
• 质子受体: 8
• 质子供体: 4
• LogD (pH = 5.5): -1.3607305
• LogD (pH = 7.4): -4.7035975
• Log P: 0.7630046
• 摩尔折射率: 117.8249 cm^3
• 极化性: 43.176983 Å^3
• 极化表面积: 148.4 Å^2
• 可自由旋转的化学键: 9
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO; Methanol; Water
• 外观: Yellow Solid
• 熔点: 176-180°C

安全信息

• 保存条件: -20°C; Hygroscopic, -20°C Freezer, Under Inert Atmosphere

药理学性质

• 作用靶点: Antimetabolites
• 生物活性机理: Thymidylate synthase inhibitor

产品相关信息

• 成盐信息: Free Base
• 应用领域: Antineoplastic agent

详细说明

Selleck Chemicals - S1192

Research Area: Cancer
Biological Activity:
Raltitrexed (Tomudex) is a thymidylate synthase inhibitor with an IC50 of 9 nM for the inhibition of L1210 cell growth. Raltitrexed (Tomudex) is an antimetabolite drug used in cancer chemotherapy. Raltitrexed (Tomudex) is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting Dihydrofolate reductase, an enzyme used in the synthesis of tetrahydrofolate, thereby preventing the synthesis of thymidylate. [1] In a study, there was an inverse relationship between reduced folate cellular content and raltitrexed IC50; this relationship did not, however, reach statistical significance. The only significant relationship was found between basal cellular folylpolyglutamate synthetase activity and raltitrexed IC50r = -0.56, p = 0.03. Tumor cells with a relatively high folylpolyglutamate synthetase activity were more sensitive to raltitrexed cytotoxic effects and vice versa.[2]References on Raltitrexed (Tomudex)[1] http://en.wikipedia.org/wiki/Raltitrexed, , [2] http://www.medscape.com/viewarticle/456039_4, ,

Toronto Research Chemicals - R100500

Folate-based inhibitor of thymidylate synthase; rapidly and extensively metabolized to its more potent polyglutamate derivatives. Antineoplastic.

参考文献

• http://en.wikipedia.org/wiki/Raltitrexed
• Jodrell, D.I., et al.: Cancer Chemother. Pharmacol., 28, 331 (1991)
• Jackman, A.L., et al.: Eur. J. Cancer, 31A, 1277 (1995)
• Eur. Pat., 1987, ICI, 239 362; CA, 108, 205094d, (synth)
• Jackman, A.L. et al., Cancer Res., 1991, 51, 5579, (pharmacol)
• Marsham, P.R. et al., J. Med. Chem., 1991, 34, 1594, (synth, pmr, ms, pharmacol)
• Keyomarsi, K. et al., J. Biol. Chem., 1993, 268, 15142, (pharmacol)
• Marsham, P.R., J. Het. Chem., 1994, 31, 603, (rev)
• Harrap, K.R., Cancer Res., 1995, 55, 2761, (pharmacol, rev)
• Gunasekara, N.S. et al., Drugs, 1998, 55, 423-435, (rev)