Methotrexate analogs. 19. Enhancement of the antitumor effect of methotrexate and 3′,5′-dichloromethotrexate by the use of lipid-soluble diesters was written by Rosowsky, A.;Yu, C. S.. And the article was included in Journal of Medicinal Chemistry in 1983.Reference of 7413-34-5 This article mentions the following:
The methotrexate (MTX) diesters I (R = CMe3, PhCH2, dodecyl, substituted benzyl, etc.) were prepared by esterification of the appropriate MTX salt with an alkyl or aralkyl halide in Me2SO or DMF and evaluated in vivo against L1210 leukemia in mice. Methotrexate bis(2,6-dichlorobenzyl) ester (I; R = 2,6-dichlorobenzyl) [86669-36-5] and methotrexate bis(6-chloropiperonyl) ester (I; R = 6-chloropiperonyl) [86688-51-9] gave a 16% increase in median life span at 20 and 40 mg/kg, resp., values which are higher than those of MTX. Some 3′,5′-dichloromethotrexate (DCM) esters were also tested. The results indicate that MTX and DCM esters are not therapeutically equivalent in mice despite the high serum esterase activity in this species, and that an up to 10-fold reduction in total given dose is feasible by this approach. In the experiment, the researchers used many compounds, for example, Sodium (S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioate (cas: 7413-34-5Reference of 7413-34-5).
Sodium (S)-2-(4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioate (cas: 7413-34-5) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. Ionic, or saltlike, amides are strongly alkaline compounds ordinarily made by treating ammonia, an amine, or a covalent amide with a reactive metal such as sodium.Reference of 7413-34-5
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics