US 10,870,625 B2 · Zwitterionic propargyl-linked antifolates useful for treating bacterial infections

Abstract

The disclosure provides compounds of the formula I and the pharmaceutically acceptable salts thereof. The variables, e.g. R1, R2, R3, R4, A, B, J, V, W, M, J and Ar are defined herein. The disclosure also provides pharmaceutical compositions comprising a compound or salt of formula I and a pharmaceutically acceptable carrier, methods of inhibiting dihydrofolate reductase (DHFR) in vitro or in vivo with a compound or salt of formula I, and methods of treating a bacterial infections, fungal infections, and protozoal infections with a compound or salt of formula I. A compound or salt of formula I can be the first and only active ingredient used in a pharmaceutical composition or method of this disclosure or may be combined with one or more additional active ingredients that are not compounds or salts of formula I.

Claims18

Dependent claims

A compound of the formula I

or a pharmaceutically acceptable salt thereof, wherein:
R is H, hydroxyl, C1-C6alkyl, or C1-C6alkoxy;
R1, R2, R3, and R4 are independently chosen from H, C1-C6alkyl, and cycloalkyl;
A and B are independently chosen from H, hydroxyl, C1-C6alkyl, and C1-C6alkoxy;
one of V and W is methoxy and the other is chosen from H, C1-C6alkyl, and C1-C6alkoxy;
J and M are independently selected from H, halogen, hydroxyl, nitro, cyano, —COOH, —CHO, —CONH2, cycloalkyl, or C1-C6alkyl in which any methylene (—CH2) is optionally replaced by O, NH, N(C1-C6alkyl), S, SO2, C(O)O, OC(O), or C(O), and which is optionally substituted with hydroxyl, amino, or halogen;
W and M may be joined to form a 5- or 6-membered carbocyclic ring or a 5- or 6-membered heterocyclic ring that contains 1, 2, or 3 heteroatoms independently chosen from N, O, and S;
and
the Ar ring is a phenyl, pyridyl, or pyrimidinyl ring substituted with at least one —COOH, or —CH2COOH, group and optionally substituted with one or more substituents independently chosen from halogen, hydroxyl, amino, C1-C6alkyl, C1-C6alkoxy, C1-C2haloalkyl, and C1-C2haloalkoxy.

6 more elements

Dependencies are inferred from the claim text.

Zwitterionic propargyl-linked antifolates useful for treating bacterial infections

Life of this patent

Zwitterionic propargyl-linked antifolates useful for treating bacterial infections

Life of this patent

Abstract

Claims18