Synthesis and immunosuppressive activity evaluation of substituted N-imidazolidin-2-ones and N-tetrahydropyrimidin-2(1H)-ones

Figures & data

Figure 1 Structure of compound 1.

Scheme 1 Synthesis of imidazolidin-2-ones 10-17 and 33-37 and tetrahydropyrimidin-2(1H)-ones 42-45. Reaction reagents and conditions: (i) AcOH, reflux; (ii) Pd/C 5%, H₂, THF, 50°C; (iii) 2-chloroethyl isocyanate, CHCl₃, reflux; (iv) 2-chloroethyl isocyanate (8 éq), microwaves, 82°C, 20 W; (v) 3-chloropropyl isocyanate, CHCl₃, reflux; (vi) Cs₂CO₃, CH₃CN, reflux; (vii) Na₂CO₃, CH₃CN, reflux.

Figure 2 Structure of compounds 10, 11 and 14.

Table I.  Inhibition of the mouse splenocyte ConA-induced proliferation by N-substituted imidazolidin-2-ones 10-17 and 33-37 and tetrahydropyrimidin-2(1H)-ones 42-45.

Compound (90 μM)	R	N	Inhibition (%) ± sem
10		1	60 ± 1.8
11		1	43 ± 1.9
12		1	< 30
13		1	< 30
14		1	91 ± 2.1
15		1	< 30
16		1	< 30
17		1	< 30
33		1	ne
34		1	< 30
35		1	< 30
36		1	ne
37		1	< 30
42		2	< 30
43		2	< 30
44		2	< 30
45		2	< 30
	Compound 1 (90 μM)		100 ± 0.0
	Cyclosporine A (5 μM)		100 ± 0.0

ne: not evaluated