Compounds for inhibiting 1-deoxy-D-xylulose-5-phosphate reductoisomerase
In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or (II) where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).
1. A compound having the chemical structure of formula (II)
wherein X is 1) a carboxylate, phosphonate, sulfate, an ester thereof, or a salt thereof, or 2) a tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4,
wherein “n is 1” and
are not simultaneously satisfied.
2. The compound of claim 1 , wherein Ar is a phenyl or a heteroaromatic group.
3. A compound having the chemical structure of formula (II)
wherein X is 1) a carboxylate, phosphonate, sulfate, an ester thereof, or a salt thereof, or 2) a tetrazol; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and wherein n is 2, 3, or 4.
4. A compound having the chemical structure of formula (II)
wherein X is a phosphonate, an ester thereof, or a salt thereof; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, wherein “n is 1” and
are not simultaneously satisfied.
5. The compound of claim 1 , selected from the group consisting of:
6. A pharmaceutical composition comprising a compound having the chemical structure of formula (II)
wherein X is 1) a carboxylate, phosphonate, sulfate, an ester thereof, or a salt thereof, or 2) tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, wherein “n is 1” and
are not simultaneously satisfied.
7. The composition of claim 6 , wherein Ar is a phenyl or a heteroaromatic group.
8. A pharmaceutical composition comprising a compound having the chemical structure of formula (II)
where X is 1) a carboxylate, phosphonate, sulfate, an ester thereof, or a salt thereof, or 2) a tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; wherein n is 2, 3, or 4.
9. A pharmaceutical composition comprising the compound of claim 5 .