Antimicrobial compounds
AssigneeAkthelia Pharmaceuticals
InventorsRoger Stromberg, Hakan Ottoson, Birgitta Agerberth, Gudmundur Gudmundsson, Erica Miraglia, Frank Nylen
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Abstract
The invention provides compounds for use in treating microbial infection in an animal. Example compounds include Pyridin-3-ylmethyl (4-((2-aminophenyl)-carbamoyl)benzyl)carbamate (“Entinostat”). The compounds can act via induction of the innate antimicrobial peptide defense system, and stimulation of autophagy.
Claims27
A method of treatment of a microbial infection in an animal, which method comprises administering to the animal a compound of formula (I):
- wherein:
- Q is selected from Q1, Q2, Q3, Q4, Q5 and Q6:
- n is 0 or 1;
- L is selected from —(CH2)m—, —C(═O)—, —(CH2)m—C(═O)—, —O—(CH2)m—C(═O)—, —O—C(═O)—(CH2)m—(C═O)—, —NH—C(═O)—, —NR—C(═O)—, —NH—(CH2)m—C(═O)—, —NR—(CH2)m—C(═O)—, —NH—C(═O)—(CH2)m—C(═O)—, —NR—C(═O)—(CH2)m—C(═O)—, —C(═O)—NH—(CH2)m—C(═O)—, and —(CH2)m—(CHRL)—C(═O)—, where m is an integer from 1 to 4;
- A and A2, together with the atoms to which they are bound, form an optionally substituted phenyl, naphthalene or heteroaryl group;
- A3, if present, is selected from H and optionally substituted C1-4alkyl;
- RN is selected from H and optionally substituted3 C1-4alkyl;
- one of B1, B2, B3, B4, and B5 is a group of formula —X—RX and the others are independently selected from H and RB;
- wherein each —RB is independently selected from halogen, —CF3, —R, —OH, —OR, —OCF3,
- —C(═O)OH, —C(═O)OR, —C(═O)R, —OC(═O)R, —NH2, —NHR, —NR2, —NO2, —C(═O)NH2, —C(═O)NHR, C(═O)NR2, —S(═O)R, —S(═O)2R, —S(═O)2NR2, or —CN;
- X is selected from a covalent bond or C1-3alkylene;
- RX is selected from —H, RXX or RXY;
- wherein:
- RXX is halogen, —CF3, —OH, —OR, —OCF3, —C(═O)OH, —NO2, —NH2, —NHR, —NR2,
- —C(═O)NH2,
- —C(═O)NR2, —S(═O)R, —S(═O)2R, —S(═O)2NR2, or —CN;
- and
- RXY is a group of formula -LX-RYY;
- wherein Lx is selected from:
- —NH—C(═O)—O—, —NH—C(═O)—NH—, —NH—C(═O)—
- —O—C(═O)—NH—, —O—C(═O)—O—, —O—(C═O)—
- —C(═O)—NH—, —C(═O)—O—, —C(═O)—;
- and RYY is selected from C1-4alkyl, C3-6cycloalkyl, —C6-14aryl, -LY-C6-14aryl,
- -LY-O—C6-14aryl-C5-6heteroaryl, -LY-C5-6heteroaryl, and -LY-O—C5-6heteroaryl, wherein
- —LY— is C1-3alkylene and wherein each of said groups is optionally substituted;
- RL is selected from halogen, —RLL, —CF3, —OH, —ORLL, —NO2, —NH2, —NHRLL, —NR2, —NH—C(═O)—RLL, —NH—C(═O)—O—RLL wherein RLL is selected from —C1-4alkyl, —C3-6cycloalkyl, -Ph, -LL-Ph, —C5-6heteroaryl, -LL-C5-6heteroaryl wherein -LL- is C1-3alkylene;
- and wherein each R is independently C1-4alkyl.
A method of treatment of a microbial infection in an animal, which method comprises administering to the animal a compound which is selected from:
- N-(2-Aminophenyl)benzamide;
- N-(2-Aminophenyl)-4-methoxybenzamide;
- N-(2-Aminophenyl)-4-nitrobenzamide;
- Benzyl (4-((2-aminophenyl)carbamoyl)-benzyl)carbamate;
- Pyridin-3-ylmethyl (4-((2-aminophenyl)-carbamoyl)benzyl)carbamate;
- Methyl 2-(4-((4-((2-aminophenyl) carbamoyl)benzyl)carbamoyl)-1H-1,2,3-triazol-1-yl)acetate;
- N1-(2-aminophenyl)-N4-(4-(dimethylamino)phenyl)terephthalamide;
- N1, N 4-bis(2-aminophenyl)terephthalamide;
- N 1-(2-aminophenyl)-N5-(4-(dimethylamino)-phenyl)glutaramide;
- and
- (9 H-fluoren-9-yl)methyl (4-((2-aminophenyl)carbamoyl)-benzyl)carbamate.
Dependencies are inferred from the claim text.