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US 2013/0158037 A1Published application
Compounds and methods for treating tuberculosis infection
AssigneeAcademia Sinica
InventorsChi-Huey Wong, Ying-Ta Wu
Life of this patent
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Abstract
The present invention provides compounds which are potent inhibitors against Lpd activity, PDH activity, and/or the growth of tubercle bacillus, and thus are useful in the treatment of tuberculosis infection and associated conditions. The present invention is further directed to in vitro- and in vzivo-based methods of inhibiting Lpd and/or PDH activity. In certain embodiments, these methods are useful in inhibiting Lpd and/or PDH activity key to a pathogen's survival.
Claims23
A method of treating a tuberculosis infection, the method comprising administering an effective amount of a compound of Formula (IX):
- or a pharmaceutically acceptable salt thereof, to a subject in need thereof;
- wherein:
- each instance of R20, R21, R22, and R23 is, independently, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl, halo, nitro, —CN, —ORa, —COORa, —OC(O)Ra, —C(O)Ra, —C(O)NRbRc, or —NRbRc;
- each instance of R24a, R24b, R25a, and R25b is, independently, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl, halo, nitro, —CN, —ORa, —COORa, —OC(O)Ra, —C(O)Ra, —C(O)NRbRc, or —NRbRc;
- or R24a and R25a are absent, and R24b and R25b together with the carbon atom to which they are attached form an optionally substituted aryl or optionally substituted heteroaryl ring;
- or R24a and R24b together with the carbon atom to which they are attached form a ═C—Ra group;
- each instance of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl;
- and
- each instance of Rb and Rc is, independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, an amino protecting group, or Rb and Rc, together with the nitrogen atom to which they are bonded are an optionally substituted heterocycloalkyl, an optionally substituted heterocycloalkenyl, or an optionally substituted heteroaryl.
6 more elements
5-10. (canceled)
16-30. (canceled)
A method of treating a tuberculosis infection, the method comprising administering an effective amount of a compound of Formula (III) or (IV):
- or a pharmaceutically acceptable salt thereof, to a subject in need thereof;
- wherein:
- each of R6, R7, and R8, independently, is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl;
- each of R9 and R10, independently, is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, halo, nitro, —CN, —ORa, —COORa, —OC(O)Ra, —C(O)Ra, —C(O)NRbRc, or —NRbRc;
- each instance of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl;
- each instance of Rb and Rc is, independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, an amino protecting group, or Rb and Rc, together with the nitrogen atom to which they are bonded are an optionally substituted heterocycloalkyl, an optionally substituted heterocycloalkenyl, or an optionally substituted heteroaryl;
- m is 0, 1, or 2;
- and
- n is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9.
6 more elements
A method of treating a tuberculosis infection, the method comprising administering an effective amount of a compound of Formula (I):
- or pharmaceutically acceptable salt thereof, or tautomer thereof, to a subject in need thereof;
- wherein:
- each instance of R1 and R2, independently, is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, or an amino protecting group;
- and
- R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, halo, nitro, CN, ORa, COORa, OC(O)Ra, C(O)Ra, C(O)NRbRc, or NRbRc;
- each instance of Ra is independently hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, or optionally substituted heteroaryl;
- and
- each instance of Rb and Rc, is, independently, hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, an amino protecting group, or Rb and Rc, together with the nitrogen atom to which they are bonded are an optionally substituted heterocycloalkyl, an optionally substituted heterocycloalkenyl, or an optionally substituted heteroaryl.
5 more elements
42-75. (canceled)
Dependencies are inferred from the claim text.