Synthesis, molecular and crystal structure of new 9,10-substituted deazaflavins

Abstract

Cyclocondensation of 6-N-(3-hydroxypropyl)aminouracyl with 2-fluoro-or 2,3-dimethoxy-substituted benzaldehydes provided the corresponding 9,10-substituted 5-deazaflavins {pyrimido[4,5-b]quinoline-2,4-(3Н,10Н)diones}. X-ray diffraction analysis was carried out for 9-methoxy-10-(3-hydroxy-propyl)-substituted 5-deazaflavin derivative.The synthesis, functional role, and biologic properties of 5-deazaflavins (pyrimido[4,5-b]-quinoline-2,4(3Н,10Н)diones) attract increasing interest in the last decade. Apart from their application as a model of co-factor for some flavin-catalyzed reactions they are accepted as new class of antitumor agents, because they possess a wide spectrum of inhibiting activity for a number of tumor cultures (NCI-H 460, HCT 116, A 431, L-1210, KB etc.) [1]. Proceeding from these data in continuation of our research on new effective antitumor drugs among the pyrimidine derivatives and its condensed systems [2][3][4] we synthesized in this study some derivatives of 5-deazaflavin containing methoxy-and 3-hydroxypropyl substituents in positions 9, 10 of the system (Scheme 1).As it is evident from the scheme, the initial compound was 6-(3-hydroxypropylamino)uracyl (I), synthesized from 6-chlorouracyl and 3-hydroxypropylamine by a usual method [5].To obtain the target 5-deazaflavin (III) we chose a method based on the interaction of 6-aminouracyl with 2-halo(chloro, bromo)-substituted aromatic aldehydes [6]. The condensation of the obtained 6-aminouracyl (I) with

Synthetic methodology of pyrimido[4,5‐b]quinoline derivatives

“…Condensation of 6‐((3‐hydroxypropyl)amino) pyrimidine‐2,4‐dione 108 with 2‐fluoro‐benzaldehyde in boiling DMF for 5–6 h, through dehydration and dehydrofluorination gave the corresponding 10‐(3‐hydroxypropyl)pyrimido[4,5‐b]quinoline‐2,4‐dione 109a in good yield. Applying this method to 2,3‐dimethoxybenzaldehyde, instead of halogen‐containing aldehyde in the ortho‐position, the corresponding 10‐(3‐hydroxypropyl)‐9‐methoxy pyrimido[4,5‐b]quinoline‐2,4(3H,10H)‐dione 109b was performed (Scheme 28) [57].…”