Synthesis, Bioactivity and SAR study of N′-(5-substituted-1,3,4-thiadiazol-2-yl)-N-cyclopropylformyl-thioureas as ketol-acid reductoisomerase Inhibitors

Figures & data

Scheme 1.  Reaction catalyzed by KARI, the known inhibitors of HOE704 and IpOHA are the analogies of Acetohydroxyacid and Methylhydroxyketolacid respectively.

Scheme 2.  Synthetic route for compounds3a–3o.

Table I.  Inhibition (%) of compounds3a–3o against rice KARI at 100 ppm in vitro.

No	R	KARI
3a	CH3	0
3b	C2H5	0
3c	n-Pr	0
3d	Iso-Pr	66.18
3e	n-Bu	100
3f	C6H5	44.91
3g	o-CH3C6H4	44.96
3h	m-CH3C6H4	37.30
3i	p-ClC6H4	82.27
3j	o-ClC6H4	22.77
3k	o-FC6H4	38.78
3l	p-NO2C6H4	32.09
3m	p-OCH3C6H4	70.34
3n	3-pyridyl	100
3o	furan	18.08
	CPD	100

Figure 1.  Frontier molecular orbitals of compound3n: A. HOMO of compound 3n; B. HOMO-1 of compound 3n.

Table II.  energies Of Homo, Homo-1 Of3N And Cpd (Hartree).

	3n	CPD
HOMO	− 0.33672	− 0.32068
HOMO-1	− 0.33989	− 0.34159

Figure 2.  PDB code: 1YVE Binding modes of compound3n in the active sites of spinach KARI: hydrogen bond and hydrophobic interaction between 3n and the rice KARI amino acid residues.