7-substituted tetracycline compounds
AssigneesParatek Pharmaceuticals, Inc., Trustees of Tufts College
InventorsMark L. Nelson, Roger Frechette, Peter Viski, Beena Bhatia, David Messersmith
Life of this patent
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Abstract
The present invention pertains, at least in part, to novel 7-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.
Claims30
A substituted tetracycline compound of Formula I:
- wherein:
- X is CHC(R13Y′Y), CR6′R6, C═CR6′R6, S, NR6, or O;
- R2, R2′, R4′, and R4″ are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety;
- R4 is NR4′R4″, alkyl, alkenyl, alkynyl, hydroxyl, halogen, or hydrogen;
- R2′, R3, R10, R11 and R12 are each hydrogen or a pro-drug moiety;
- R5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, alkyl carbonyloxy, or aryl carbonyloxy;
- R6 and R6′ are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- R7 is alkynyl substituted with an aryl;
- R9 hydrogen
- R8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- R13 is hydrogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- and
- Y′ and Y are each independently hydrogen, halogen, hydroxyl, cyano, sulfhydryl, amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl, and pharmaceutically acceptable salts thereof.
A substituted tetracycline compound of Formula I:
- wherein:
- X is CHC(R13Y′Y), CR6′R6, C═CR6′R6, S, NR6, or O;
- R2, R2′, R4′, and R4″are each independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, aryl, heterocyclic, heteroaromatic or a prodrug moiety;
- R4 is NR4′R4″, alkyl, alkenyl, alkynyl, aryl, hydroxyl, halogen, or hydrogen;
- R2′, R3, R10, R11 and R12 are each hydrogen or a pro-drug moiety;
- R5 is hydroxyl, hydrogen, thiol, alkanoyl, aroyl, alkaroyl, aryl, heteroaromatic, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, arylalkyl, alkyl carbonyloxy, or aryl carbonyloxy;
- R6 and R6′ are each independently hydrogen, methylene, absent, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- R7 is substituted alkynyl, wherein said substituted alkynyl is substituted with a tetracycline moiety;
- R9 is hydrogen;
- R8 is hydrogen, hydroxyl, halogen, thiol, alkyl, alkenyl, alkynyl, aryl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- R13 is hydrogen, hydroxy, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl;
- and
- Y′ and Y are each independently hydrogen, halogen, hydroxyl, cyano, sulfhydryl, amino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, or an arylalkyl, and pharmaceutically acceptable salts thereof.
A tetracycline compound selected from the group consisting of:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A substituted tetracycline compound selected from the group consisting of:
- and pharmaceutically acceptable salts, esters and prodrugs thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
A tetracycline compound of the formula:
- and pharmaceutically acceptable salts, prodrugs and esters thereof.
Dependencies are inferred from the claim text.