(2S)-2-[(4-{2-[(6R)-2-amino-4-oxo-4H,4aH,5H,6H,7H,8H-pyrido[2,3-d]pyrimidin-6-yl]ethyl}phenyl)formamido]pentanedioic acid

• ChemBase ID: 172375
• Molecular Formular: C21H25N5O6
• Molecular Mass: 443.4531
• Monoisotopic Mass: 443.18048355
• SMILES: N1=C(N=C2C(C1=O)C[C@H](CN2)CCc1ccc(cc1)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N
• Canonical SMILES: OC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)CC[C@H]1CNC2=NC(=NC(=O)C2C1)N
• InChI: InChI=1S/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,14-15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H3,22,23,25,26,30)/t12-,14?,15+/m1/s1
• InChIKey: ZIXNNHANGXIXPX-ATFAPYMMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-2-[(4-{2-[(6R)-2-amino-4-oxo-4H,4aH,5H,6H,7H,8H-pyrido[2,3-d]pyrimidin-6-yl]ethyl}phenyl)formamido]pentanedioic acid
• IUPAC Traditional name: (2S)-2-[(4-{2-[(6R)-2-amino-4-oxo-4aH,5H,6H,7H,8H-pyrido[2,3-d]pyrimidin-6-yl]ethyl}phenyl)formamido]pentanedioic acid
• Synonyms: N-[4-[2-[(6R)-2-Amino-3,4,5,6,7,8-hexahydro-4-oxopyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl]-L-glutamic Acid; LY 264618; Lometrexol

Database IDs

• CAS Number: 106400-81-1
• PubChem SID: 164228285
• PubChem CID: 71749832

CALCULATED PROPERTIES

• Acid pKa: 3.0429292
• H Acceptors: 10
• H Donor: 5
• LogD (pH = 5.5): -3.0199182
• LogD (pH = 7.4): -5.7805386
• Log P: -1.5574178
• Molar Refractivity: 111.4643 cm^3
• Polarizability: 42.420364 Å^3
• Polar Surface Area: 183.54 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

DETAILS

Toronto Research Chemicals - L469465

It is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Lometrexol has activity against tumors which are refractory to other drugs, notably Methotrexate.

REFERENCES

• Gibbs, D., et al.: Cancer Res., 65, 11721 (2005)
• Gangjee, A., et al.: J. Med. Chem., 48, 5329 (2005)
• Hilgenbrink, A., et al.: J. Pharm. Sci., 94, 2135 (2005)