Design, synthesis and evaluation of 2,4-diarylpyrano[3,2-c]chromen-5(4H)-one as a new class of non-purine xanthine oxidase inhibitors

Figures & data

Figure 1. Design strategy.

Scheme 1. Synthesis of 2,4–diphenyl pyrano[3,2-c]coumarins.

Table 1. Percentage yield of the model reaction with various catalysts.

Entry	Catalyst (10 mol%)	Yield (%)
1	AlCl3	38
2	FeCl3	35
3	I2	32
4	BF3	25
5	ZnCl2	50
6	SnCl2	41
7	H3BO3	13
8	Silica (200–400 #)	18
9	SiO2-ZnCl2 (60–120 #)	55
10	SiO2-ZnCl2 (100–200 #)	62
11	SiO2-ZnCl2 (200–400 #)	82

Table 2. Isolated yields, IC₅₀ values and type of inhibition.

Code	Structure	Yield (%)	IC50 (µM)
HV-1		82	25.42
HV-2		84	78.31HV-3
		83	80.21
HV-4		85	65.32
HV-5		83	72.1
HV-6		68	16.71
HV-7		72	21.31
HV-8		75	8.21
HV-9		84	75.21
HV-10		69	56.21
HV-11		75	2.21
HV-12		81	4.31
HV-13		85	85.32
HV-14		71	26.43
HV-15		60	59.21
HV-16		81	86.32
HV-17		70	27.51
HV-18		80	33.21
HV-19		78	43.21
HV-20		53	36.81
Allopurinol			8.79

Figure 2. Lineweaver–Burk plot of HV-11.

Table 3. Molecular properties of some selected hybrids.

Entry	Compound	TPSA	Mol. wt.	ClogP	nOHNH	nON	nrotb	Volume	No. of violations
1	HV-11	35.539	360	4.602	0	3	2	310.742	0
2	HV-12	35.539	404	5.863	0	3	2	364.022	1
3	HV-8	35.539	404	6.36	0	3	2	364.022	1
4	HV-16	81.363	399	5.111	0	6	3	343.364	1
5	HV-13	81.363	399	5.135	0	6	3	343.364	1
6	HV-6	81.363	414	4.823	0	5	4	371.121	0