Arylnaphthalene compounds as vacuolar-ATPase inhibitors and the use thereof
AssigneesPurdue Research Foundation, Trustees of Boston University
InventorsVincent Jo Davisson, Aaron Raymond Lindstrom, Naoaki Fujii, Robert A. Davey
Life of this patent
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Abstract
Ebola virus and Marburg virus are filoviruses and are responsible for outbreaks that cause up to 90% fatality, including the recent outbreak in West Africa that has resulted in over 11,000 deaths. The present disclosure generally relates to series novel arylnaphthalene compounds, having a formula (I) or a pharmaceutically acceptable salt thereof, as a vacuolar-ATPase inhibitor that are useful for the treatment for a broad spectrum of viral infections, including those infections caused by filoviruses. Pharmaceutical composition matters and methods of use are within the scope of this invention.
Claims14
A compound having a formula
- or a pharmaceutically acceptable salt thereof, wherein
- A is CR2, CH2, S, NH, NR, wherein R is alkyl;
- B is hydrogen (H), deuterium (D), or fluorine (F);
- X is C═O, CR2, CH2, CHR, S, NH, NR, wherein R is unsubstituted alkyl;
- Y is O, CF2, CH2, CHR, S, NH, NR, wherein R is an alkyl;
- R1 is hydrogen, alkyl, alkylamide, alkenyl, alkenylamide, alkenylamino, alkynyl, alkynylamide, alkynylamino, heterocyclyl, cycloalkyl, cycloalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl;
- R2, R3, and R4 are each independently selected from the group consisting of hydrogen, deuterium, —CN, and a halo.
A method for treating a patient with an infection with Ebola virus or Marburg virus, comprising the step of administering a therapeutically effective amount of one or more compounds, together with one or more carriers, diluents, or excipients, to a patient in need of relief from said infection, the compound having formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- A is CR2, CH2, S, NH, or NR, wherein R is alkyl;
- B is hydrogen (H), deuterium (D), or fluorine (F);
- X is CR2, CH2, CHR, S, NH, or NR, wherein R is unsubstituted alkyl;
- Y is O, CF2, CH2, CHR, S, NH, or NR, wherein R is an alkyl;
- R1 is hydrogen, alkyl, alkylamide, alkenyl, alkenylamide, alkenylamino, alkynyl, alkynylamide, alkynylamino, heterocyclyl, cycloalkyl, cycloalkenyl, acyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl;
- R2, R3, and R4 are each independently selected from the group consisting of hydrogen, deuterium, —CN, and a halo.
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- A is CH2;
- B is hydrogen (H), deuterium (D), or fluorine (F);
- X is O or S;
- Y is O, CF2, CH2, CHR, S, NH, or NR, wherein R is an alkyl;
- R1 is
- —CH2CH2O(CH2)nR7, —CH2CH2CH2O(CH2)nR7, —CH2CH2CH2CH2O(CH2)nR7, or —CH2(CH2)nR7, wherein n=1-4;
- R2, R3, and R4 are each independently selected from the group consisting of hydrogen, deuterium, —CN, —CF3, and halo;
- R7 is
- wherein Z is halogen, C1˜C3 alkyl, —CF3, —CN, or —CONR2, wherein R is hydrogen or C1˜C3 alkyl, and * represents site for Attachment.
A compound selected from:
A compound having a formula
- or a pharmaceutically acceptable salt thereof, wherein
- A is C═O, CR2, S, NH, NR, wherein R is alkyl;
- B is hydrogen (H), deuterium (D), or fluorine (F);
- X is C═O, CR2, CH2, CHR, O, S, NH, NR, wherein R is unsubstituted alkyl;
- Y is O, CF2, CH2, CHR, S, NH, NR, wherein R is an alkyl;
- R1 is hydrogen, alkyl, alkylamide, alkenyl, alkenylamide, alkenylamino, alkynyl, alkynylamide, alkynylamino, heterocyclyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl, arylalkyl, arylalkenyl, or arylalkynyl;
- R2, R3, and R4 are each independently selected from the group consisting of hydrogen, deuterium, —CN, —CF3, and halo.
A method for treating a patient with an infection with Ebola virus or Marburg virus, comprising the step for Administering a therapeutically effective amount of one or more compounds, together with one or more carriers, diluents, or excipients, to a patient in need of relief
- from said infection, the compound having formula (I):
- or a pharmaceutically acceptable salt thereof, wherein
- A is CH2;
- B is hydrogen (H), deuterium (D), or fluorine (F);
- X is O or S;
- Y is O, CF2, CH2, CHR, S, NH, or NR, wherein R is alkyl;
- R1 is alkylamide, alkenylamide, alkenylamino, alkynylamide, alkynylamino, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or arylalkenyl;
- and
- R2, R3, and R4 are each independently selected from the group consisting of hydrogen, deuterium, —CN, and halo.
Dependencies are inferred from the claim text.