Amino methylated 2-pyridinones
Novel amino methylated 2-pyridinones, precursors, intermediates, and derivatives; the methods for the preparation of the same; uses of the same for inhibiting pili formation in bacteria; and pharmaceutical compositions comprising these compounds are described in this application. The present compounds may be employed to inhibit biofilm formation and thereby inhibit adherence of bacteria to a host cell.
1. The amino methylated 2-pyridinone corresponding to Formula VIa or a salt thereof:
wherein
R 2 and R 3 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl or heterocyclo or, in combination with the nitrogen atom to which they are bonded, form a heterocyclo, provided at least one of R 2 and R 3 is other than hydrogen;
R 4 and R 5 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, or heterocyclo, provided at least one of R 4 and R 5 is other than hydrogen;
X 5 is —C(H)—;
X 33 is an electron pair or oxo;
X 44 is hydrogen or hydrocarbyl;
X 55 is —CO 2 X 555 ; and
X 555 is hydrogen, a cation, hydrocarbyl, substituted hydrocarbyl, or heterocyclo.
2. The amino methylated 2-pyridinone of claim 1 wherein X 44 is hydrogen or alkyl.
3. The amino methylated 2-pyridinone of claim 1 wherein X 555 is an alkali metal.
4. The amino methylated 2-pyridinone of claim 1 wherein R 2 and R 3 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl or heterocyclo, provided at least one of R 2 and R 3 is other than hydrogen.
5. The amino methylated 2-pyridinone of claim 1 wherein (i) R 2 and R 3 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl or heterocyclo, and (ii) X 44 is hydrogen or hydrocarbyl.
6. The amino methylated 2-pyridinone of claim 1 wherein R 2 is alkyl.
7. The amino methylated 2-pyridinone of claim 1 wherein R 2 and R 3 , in combination with the nitrogen atom to which they are bonded form a heterocyclo.
8. The amino methylated 2-pyridinone of claim 1 wherein R 4 is alkyl or aryl.
9. The amino methylated 2-pyridinone of claim 1 wherein R 5 is alkyl.
10. A compound having the formula
wherein R 1 is phenyl, R 2 is methyl, R 3 is NMe 2 and Me is methyl.
11. A process for inhibiting adherence of a bacteria to a host cell, the process comprising treating the bacteria with a compound of claim 1 or a salt thereof.
12. A process for inhibiting adherence of a bacteria to a host cell, the process comprising treating the bacteria with a compound of claim 2 or a salt thereof.
13. A compound having the formula
wherein R 1 is phenyl, R 2 is —CH 2 -1-naphthyl, R 3 is NMe 2 , and Me is methyl.
14. A compound having the formula
wherein R 1 is phenyl, R 2 is —CH 2 -1-naphthyl, R 3 is morpholine.
15. A compound having the formula
wherein R 1 is cyclopropyl, R 2 is —CH 2 -1-naphthyl, R 3 is NMe 2 and Me is methyl.