Pelitrexol

• CAT Number: I008630
• CAS Number: 446022-33-9
• Molecular Formula: C20H25N5O6S
• Molecular Weight: 463.509
• Purity: ≥95%
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: (2S)-2-[[5-[2-[(6S)-2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pyrido[2,3-d]pyrimidin-6-yl]ethyl]-4-methylthiophene-2-carbonyl]amino]pentanedioic acid
• InChI: InChI=1S/C20H25N5O6S/c1-9-6-14(18(29)23-12(19(30)31)3-5-15(26)27)32-13(9)4-2-10-7-11-16(22-8-10)24-20(21)25-17(11)28/h6,10,12H,2-5,7-8H2,1H3,(H,23,29)(H,26,27)(H,30,31)(H4,21,22,24,25,28)/t10-,12-/m0/s1
• InChIKey: QXOPTIPQEVJERB-JQWIXIFHSA-N
• SMILES: CC1=C(SC(=C1)C(=O)NC(CCC(=O)O)C(=O)O)CCC2CC3=C(NC2)NC(=NC3=O)N

Pelitrexol is a GARFT inhibitor, and is also a water soluble antifolate with anti-proliferative activity. Pelitrexol inhibits activity of glycinamide ribonucleotide formyltransferase (GARFT), the first folate-dependent enzyme of the de novo purine synthesis pathway essential for cell proliferation. Enzyme inhibition reduces the purine nucleotides pool required for DNA replication and RNA transcription. As a result, this agent causes cell cycle arrest in S-phase, and ultimately inhibits tumor cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Reference

1:Org Lett. 2006 Apr 13;8(8):1653-5. Efficient chemoenzymatic synthesis of pelitrexol via enzymic differentiation of a remote stereocenter.Hu S,Kelly S,Lee S,Tao J,Flahive E, PMID: 16597133 DOI: 10.1021/ol0602755 Abstract: [structure: see text] An efficient chemoenzymatic process is described for the synthesis of pelitrexol, a novel GARFT inhibitor. The remoteness of this molecule/’s stereocenter in the tetrahydropterin moiety from the terminal carbonyl group provided a significant challenge in synthesis. The introduction of an oxalamic ester adjacent to the stereocenter dramatically enhanced an enzyme/’s enantioselectivity for hydrolysis at the terminal ester, producing the desired S-acid with high optical purity and yield. The recycling of the /wrong/ enantiomer is achieved via a dehydrogenation/hydrogenation strategy.