Matriptase inhibitors and uses thereof against orthomyxoviridae infections

A method of treating an influenza type A, B or C infection in a subject, said method comprising administering to said subject a therapeutically effective amount of a compound of formula (1) or a composition comprising said compound of formula (1) to said subject, wherein said compound of formula (1) is:

• or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein
• R12 is H, NH2 or NHR7;
• wherein R7 is
• R13 is H, NH2 or NHR7;
• wherein R7 is an alkyl, aryl, (C═O)-alkyl, (C═O)-aryl, SO2-alkyl or SO2-aryl, C(═NH)—NH2, C(═NH)—NHalkyl, C(═NH)—NHaryl or one or more amino acids residues in (L) or (D) configuration;
• R1 is H, NH2 or NHR7;
• wherein R7 is an alkyl, aryl, (C═O)-alkyl, (C═O)-aryl, SO2-alkyl or SO2-aryl, C(═NH)—NH2, C(═NH)—NHalkyl, C(═NH)—NHaryl or one or more amino acids residues in (L) or (D) configuration;
• R2 and R5 are independently —CH2—R8 or
• wherein R8 is (CH2)n-NH(C═NH)NH—R14 or (CH2)n-NH—R14, wherein,
• n is 1 to 4;
• m is 0 to 3;
• R10 is —C(═NH)—NH2, NH2 or NH alkyl;
• and
• R14 is H, alkyl, NH2, NO2 or COalkyl;
• R3 is a linear alkyl;
• an alkyl substituted with (CO)NH2, (CO)OH, NH2, NHCO-alkyl, NHCO-aryl, NHSO2-alkyl, NHSO2-aryl or heteroaryl;
• an aryl, a substituted aryl, an heteroaryl or a substituted heteroaryl;
• R4 is an alkyl, an aryl, a substituted alkyl, a substituted aryl, an heteroaryl or a substituted heteroaryl;
• R6 is
• wherein W, X, Y and Z are independently N or CH;
• V is independently O, NH, NCH3 or S;
• R11 is H, CO2H, CONH-alkyl, CONH-aryl, aryl, heteroaryl, halide or CO-(amino acid residue in (L) or (D) configuration)q, wherein q is 1 or 2;
• and
• wherein the one or more amino acids residue is isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, arginine, alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, proline, serine, tyrosine, beta-alanine, 3-amino-propionic acid, 2,3-diamino propionic acid, alpha-aminoisobutyric acid, 4-amino-butyric acid, N-methylglycine, hydroxyproline, ornithine, citrulline, t-butylalanine, t-butylglycine, N-methylisoleucine, phenylglycine, cyclohexylalanine, cyclopentylalanine, cyclobutylalanine, cyclopropylalanine, cyclohexylglycine, cyclopentylglycine, cyclobutylglycine, cyclopropylglycine, norleucine, norvaline, 2-napthylalanine, pyridylalanine, 3-benzothienyl alanine, 4-chlorophenylalanine, 2-fluorophenylalanine, 3-fluorophenylalanine, 4-fluorophenylalanine, penicillamine, 1,2,3,4-tetrahydro-isoquinoline-3-carboxylix acid, beta-2-thienylalanine, methionine sulfoxide, homoarginine, N-acetyl lysine, 2-amino butyric acid, 2-amino butyric acid, 2,4,-diaminobutyric acid, p-aminophenylalanine, N-methylvaline, selenocysteine, homocysteine, homoserine, cysteic acid, epsilon-amino hexanoic acid, delta-amino valeric acid, or 2,3-diaminobutyric acid.