Synthesis of 2H-pyrano[3,2-g]quinolin-2-ones containing a pyrimidinone moiety and characterization of their anticoagulant activity via inhibition of blood coagulation factors Xa and XIa

Abstract

The reactions of 7-hydroxy-1,2,2,4-tetramethylhydroquinoline-6-carbaldehydes with methyl 3-oxopentanedioate were used to synthesize 3-oxo-3-(6,8,8,9-tetramethyl-2-oxo-2H-pyrano[3,2-g]quinolin-3-yl)propanoates with various degrees of hydrogenation in the pyridine ring, the condensation of which with carboximidamides provided a series of new 6,8,8,9-tetramethyl-3-(6-oxo-1,6-dihydropyrimidin-4-yl)-2H-pyrano[3,2-g]quinolin-2-ones. It was found that some compounds of this class exhibited relatively high inhibitory activity against the blood coagulation factors Xа and XIa.

Annulated Heterocyclic[g]Coumarin Composites: Synthetic Approaches and Bioactive Profiling

“…In comparison, the positive control, rivaroxaban, decreased the activities to 94 % and 8 %, respectively. This suggests that compound ( 164 ) exhibited moderate selectivity towards Factor 11a, presenting itself as a promising candidate for a novel anticoagulant agent [110] …”

“…Following this, the compound reacted with ethyl 3-oxobutyrate (2) to create the coumarin derivative (108). Next, compound ( 108) was nitrated at C6 using anhydrous aluminium nitrate, producing compound (109), which underwent deamination of its amino group via a reaction with H 2 SO 4 and acetic anhydride, resulting in compound (110). The final stage involved treating compound (110) with Sn and HCl to obtain the desired compound (111).…”

“…Next, compound ( 108) was nitrated at C6 using anhydrous aluminium nitrate, producing compound (109), which underwent deamination of its amino group via a reaction with H 2 SO 4 and acetic anhydride, resulting in compound (110). The final stage involved treating compound (110) with Sn and HCl to obtain the desired compound (111). The imidazolocoumarin derivatives (112a and 112b) were synthesized by subjecting compound (111) to phenylmethanal and cinnamal, respectively, as depicted in Scheme 19.…”

“…This suggests that compound (164) exhibited moderate selectivity towards Factor 11a, presenting itself as a promising candidate for a novel anticoagulant agent. [110] Potapov and associates [111] used the same synthesis process to create a different series of dihydropyridocoumarins in an additional experimental study. Compound (165) exhibited noteworthy suppression capabilities against factors 10a and 11a, as depicted in Figure 11.…”

New Blood Coagulation Factor XIIa Inhibitors: Molecular Modeling, Synthesis, and Experimental Confirmation

“…Synthesis techniques and characteristics of compounds 41453 (6'-6'-dimethyl-2,3,4,5',6',9hexahydrodispiro[ß-carboline-1,1'-pyrrolo[3,2,1-ij]quinoline-4',1"-cyclohexane]-2'-one) and 225006 (6,8,8,9-tetramethyl-3-[2-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-4-yl]-6,7,8,9-tetrahydro-2Hpyrano-[3,2-g]quinolin-2-one) were previously described in our works [43] and [44], respectively. Undescribed compound 30901 (2-amino-8'-methoxy-4',4',6'-trimethyl-2',5-dioxo-5',6'-dihydro-2'H,4'H,5H-spiro[pyrano[3,2-c]chromene-4,1'-pyrrolo[3,2,1-ij]quinoline]-3-carbonitrile) was obtained by the three-component cyclocondensation of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1,2diones Ia with malononitrile and 4-hydroxycoumarin according to our previously developed method [45] in the environment of ethanol and the presence of N-methylpiperazine as a catalyst (see Scheme 1).…”