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

• ChemBase ID: 72570
• Molecular Formular: C21H22N4O6S
• Molecular Mass: 458.48758
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-2-[(5-{methyl[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl]amino}thiophen-2-yl)formamido]pentanedioic acid
• IUPAC Traditional name: (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
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

• Acid pKa: 3.9605484
• H Acceptors: 8
• H Donor: 4
• LogD (pH = 5.5): -1.3607305
• LogD (pH = 7.4): -4.7035975
• Log P: 0.7630046
• Molar Refractivity: 117.8249 cm^3
• Polarizability: 43.176983 Å^3
• Polar Surface Area: 148.4 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol; Water
• Apperance: Yellow Solid
• Melting Point: 176-180°C

Safety Information

• Storage Condition: -20°C; Hygroscopic, -20°C Freezer, Under Inert Atmosphere

Pharmacology Properties

• Target: Antimetabolites
• Mechanism of Action: Thymidylate synthase inhibitor

Product Information

• Salt Data: Free Base
• Application(s): Antineoplastic agent

DETAILS

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.

REFERENCES

• 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)