Method of identifying inhibitors of DHODH
The present invention provides a compound capable of binding to the ubiquinone binding site of DHODH which contains a non-aromatic ring system as a core structure, a group capable of interacting with structural elements of subsite 2 or 3 of the ubiquinone binding site of DHODH and a group capable of interacting hydrophobically with structural elements of subsite 1 of the ubiquinone binding site of DHODH. Furthermore, the present invention provides a compound capable of binding to the ubiquinone binding site of DHODH which contains an aromatic ring system as a core structure, a group capable of interacting with residues His 56 and/or Tyr 356 of subsite 3 of the ubiquinone binding site of DHODH and a group capable of interacting hydrophobically with structural elements of subsite 1 of the ubiquinone binding site of DHODH.
1. A compound of formula (III)
wherein
A is C or S
R 1 is H or OH, except when A is S R 1 is H
R 2 is H or OH
R 3 is CH 3 or CF 3 , and
n is an integer value between CH 1 and CH 4 inclusive.
2. A compound of claim 1 is:
3. A compound of claim 1 is:
4. A compound of claim 1 is:
5. A compound of claim 1 is:
6. A compound of claim 1 is:
7. A compound of claim 1 is:
8. A compound of claim 1 is:
9. A compound of claim 1 is:
10. A compound of claim 1 is: