Heterocyclic antiviral compounds

A compound according to formula I wherein:

• one of R1 and R2 is phenyl optionally substituted with one to four substituents selected independently in each incidence from the group consisting of halogen, C1-6 alkyl, cyano and C1-6 alkoxy;
• and, the other of R1 and R2 is hydrogen;
• R5 is hydroxy, NR6aR6b, C1-6 alkoxy or benzyloxy;
• R6 is hydrogen, C1-6 alkyl, C1-3 haloalkyl, C1-6 hydroxyalkyl or oxo-C1-6 alkyl;
• R6a, R6b, R6c and R6d are independently hydrogen or C1-3 alkyl with the proviso that at least one of R6c is hydrogen;
• X1 is selected from the group consisting of (i)-(xiii) and (xiv):
• wherein
• X2 is N or CH;
• A1 is C1-6 straight or branched alkylene optionally substituted by a phenyl ring or phenylene;
• m is zero to two;
• wherein R4 is C(═O)R5 or hydrogen;
• with the proviso that A1 is other than phenylene;
• wherein:
• R7 is C3-7 cycloalkyl, (CH2)nCOR5, heteroaryl selected from the group consisting of pyridine, pyrimidine, pyrazine and pyridazine said heteroaryl optionally substituted with C1-3 alkyl or C1-3 haloalkyl;
• n is 1 to 3;
• wherein X3 is —S(O)2— or —C(O)—;
• wherein
• R9 and R10 are (A) together a group (CH2)2X4(CH2)2, (CH2)2CH(R12)CH2, or (CH2)2SO2;
• or, (B) independently R10 is hydrogen or C1-3 alkyl and R9 is —SO2C1-6 alkyl, C1-6 hydroxyalkyl, xA, xB or xC;
• X4 is O, S(O)m, NR11 or CH(NHSO2C1-6 alkyl);
• R11 is R6d, —C(O)C1-6 alkyl, S(O)2C1-6 alkyl;
• R12 is hydrogen, hydroxyl or C1-10 acyloxy;
• m is zero to two;
• and,
• wherein R6e is C1-6 hydroxyalkyl or oxo-C1-6 alkyl;
• and,
• wherein R13 is C3-5 cycloalkyl or C1-3 alkynyl;
• R3 is selected from the group consisting of (i), (ii), (iii) (iv) and (v) wherein:
• (i) C3-7 cycloalkyl substituted one or more substituents selected from the group consisting of C1-6 alkoxy, CO2R6d, CONR6aR6b, fluorine, —NR6dCO C1-3alkyl, —NR6dSO2 C1-3 alkyl, and C1-10 acyloxy or two hydrogens on the same carbon together are replaced by oxygen (oxo) provided that R3 is not 4-oxo-cyclohexyl or 3-oxo-cyclobutyl and when the cycloalkyl is substituted with fluorine, R2 is meta-cyano-phenyl;
• wherein:
• A2 is C1-6 straight or branched alkylene wherein one carbon atom can optionally be replaced by —O—, —S(O)m—, or NR5 providing the carbon replaced is not bonded to the heterocyclic nitrogen or the terminal carboxy moiety or A2 is absent and R5 is tert-butyl;
• X5 is C(═O) or CH2;
• r is zero or one;
• wherein A3 is C1-6 alkylene said alkylene optionally substituted with C5-7 cycloalkyl or A3-COR5 together represent NH(CH2)nCOR5;
• n is one to three;
• wherein:
• X6 is C(O)R8 or S(O)2C1-6 alkyl;
• R8 is C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkyl;
• C1-6 alkoxy or C1-6 alkylamino;
• with the proviso that when R3 is (iv), X1 is not (x), (xi) or (xii);
• (v) phenylamine optionally substituted with —SO2NH2;
• and,
• pharmaceutically acceptable salts, hydrates and solvates.