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US 9,919,998 B2Granted
Antibacterial agents: Nα-aroyl-N-aryl-phenylalaninamides
AssigneeRutgers, The State University of New Jersey
InventorsRichard H. Ebright, Yon W. Ebright, Soma Mandal, Richard Wilde, Shengjian Li
Life of this patent
Estimating the term…
Abstract
The invention provides compounds having activity as bacterial RNA polymerase inhibitors and antibacterial agents, as well as compositions comprising the compounds and methods for their use. Specifically, phenylalanineamide and tyrosinamide compounds are disclosed that have inhibitory activity toward mycobacterium tuberculosis RNA polymerase. Use of these compounds in the treatment or prevention of M. tuberculosis infections in a mammal, is disclosed.
Claims23
A compound of formula (V), or a salt thereof:
- wherein T and U each is carbon;
- V is carbon;
- A and B each is carbon;
- E is one of carbon (CH), nitrogen, oxygen, and sulfur;
- G is one of hydrogen, halogen, carbon (CH), nitrogen, oxygen, and sulfur;
- J is carbon, and J, together with T, U, V, and two additional carbon atoms, forms a phenyl;
- R1 and R2 each independently is hydrogen, halogen, alkyl, alkoxy-substituted alkyl, or alkoxy, each optionally substituted by halogen;
- R3 and R4 each independently is hydrogen, halogen, hydroxy;
- —O—C(═O)—C1-C4alkyl, —O—C(═O)-phenyl, or morpholino
- R5, R6, R7, and R8 each independently is absent, hydrogen, halogen, or alkyl which is optionally substituted by halogen;
- or R5 and R6, together with E, form a cycle containing 5 to 9 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen, amine, alkyl, or acyl;
- or R7 and R8, together with G, form a cycle containing 5 atoms selected from carbon and nitrogen;
- and
- R9, R10, and R11 each independently is hydrogen or halogen;
- provided that when E is carbon, G is hydrogen or is the carbon atom of an unsubstituted methyl group, R1, R2, R3, R4, R9, R10, and R11 are hydrogen;
- then E is bonded to no more than two hydrogen atoms and no more than two fluorine atoms;
- provided that when E is oxygen, G is hydrogen, and R1, R3, R9, R10, and R11 are hydrogen;
- then E is not bonded to hydrogen or unsubstituted ethyl;
- and
- provided that when E is oxygen, G is hydrogen, and R1, R2, R3, R9, R10, and R11 are hydrogen, and R9 is chlorine;
- then E is not bonded to hydrogen or unsubstituted methyl.
18 more elements
A compound of formula (V), or a salt thereof:
- wherein T and U each is carbon;
- V is carbon;
- A and B each is carbon;
- E is one of carbon (CH), nitrogen, oxygen, and sulfur;
- G is one of carbon (CH), nitrogen, oxygen, and sulfur;
- J is carbon, and J, together with T, U, V, and two additional atoms, forms a phenyl;
- R1 and R2 each independently is hydrogen, halogen, or is alkyl which is optionally substituted by halogen;
- R3 and R4 each independently is hydrogen, halogen, or hydroxy;
- and
- R6 and R7 are absent and E and G, together with A and B, form a cycle containing 5 to 6 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen or alkyl;
- R5 and R8 each independently is absent, hydrogen, halogen, or alkyl;
- and
- R9, R10, and R11 each independently is hydrogen or halogen.
10 more elements
A compound of formula (V), or a salt thereof:
- wherein T and U each is carbon;
- V is carbon;
- A and B each is carbon;
- E is one of carbon (CH), nitrogen, oxygen, and sulfur;
- G is one of hydrogen, halogen, carbon (CH), nitrogen, oxygen, and sulfur;
- J is sulfur, and J, together with T, U, V, and one additional atom, forms a thiophenyl;
- R1 and R2 each independently is hydrogen, halogen, or alkyl that is optionally substituted by halogen;
- R3 and R4 each independently is hydrogen, halogen, hydroxy, or —O—C(═O)—C1-C4alkyl;
- R5, R6, R7, and R8 each independently is absent, hydrogen, halogen, or alkyl which is optionally substituted by halogen;
- or R5 and R6, together with E, form a cycle containing 5 to 6 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen, amine, alkyl, or hydroxy-substituted alkyl;
- or R6 and R7 are absent and E and G, together with A and B, form a cycle containing 5 to 6 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen or alkyl which is optionally substituted by halogen;
- and
- R9, R10, and R11 each independently is hydrogen or halogen;
- provided that when E is carbon, G is hydrogen or is the carbon atom of an unsubstituted methyl group, and R1, R2, R3, R4, R9, R10, and R11 are hydrogen;
- then E is bonded to no more than two hydrogen atoms and no more than two fluorine atoms;
- provided that when E, and G are carbon, R1 is hydrogen, R2 is hydrogen or methyl, and R3, R4, R9, R10, and R11 are hydrogen;
- then A, B, E, and G are not part of a phenyl cycle;
- provided that when E is nitrogen, G is hydrogen, and R1, R2, R3, R4, R9, R10, and R11 are hydrogen;
- then E, R5, and R6 are not part of a morpholine cycle;
- provided that when E is oxygen, G is hydrogen, and R1, R3, R9, R10, and R11 are hydrogen;
- then E is not bonded to hydrogen or unsubstituted ethyl;
- and
- provided that when E is oxygen, G is hydrogen, and R1, R2, R3, R9, R10, and R11 are hydrogen, and R9 is chlorine;
- then E is not bonded to hydrogen or unsubstituted methyl.
21 more elements
A compound of formula (V), or a salt thereof:
- wherein T and U each is carbon;
- V is carbon;
- A and B each is carbon;
- E is one of carbon (CH), nitrogen, oxygen, and sulfur;
- G is one of hydrogen, halogen, carbon (CH), nitrogen, oxygen, and sulfur;
- J is carbon, and J, together with T, U, V, and two additional atoms, forms a phenyl;
- R1 and R2, together with T and U, form a cycle containing 5 to 6 atoms selected from carbon, and nitrogen;
- R3 and R4 each independently is hydrogen, halogen, or hydroxy;
- R5, R6, R7, and R8 each independently is absent, hydrogen, halogen, or alkyl which is optionally substituted by halogen;
- or R5 and R6, together with E, form a cycle containing 5 to 6 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen, amine, or alkyl;
- or R6 and R7 are absent and E and G, together with A and B, form a cycle containing 5 to 6 atoms selected from carbon, nitrogen, oxygen, and sulfur, said cycle optionally substituted with halogen or alkyl which is optionally substituted by halogen;
- and
- R9, R10, and R11 each independently is hydrogen or halogen.
10 more elements
A compound selected from the group consisting of:
- and salts thereof.
Dependencies are inferred from the claim text.